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{{Infobox scientist
{{Infobox scientist
| name = Craig M. Crews
| name = Craig M. Crews
| image =
| image = Craig Crews.jpg
| birth_date = {{b-da|June 1, 1964}}
| birth_date = {{b-da|June 1, 1964}}
| birth_place =
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'''Craig M. Crews''', Ph.D. (born June 1, 1964) is an American scientist at Yale University. He is the John C. Malone Professor of [[molecular biology|Molecular, Cellular, and Developmental Biology]], and also holds joint appointments in the departments of [[Chemistry]] and [[Pharmacology]]. Crews is a former Editor of Cell Chemical Biology<ref>{{cite web|url=http://www.cell.com/cell-chemical-biology/editors|title=Staff and Editorial Board|website=Cell Chemical Biology|accessdate= February 28, 2018}}</ref> and the Executive Director of the Yale Center for Molecular Discovery.<ref>{{cite web|url=http://ycmd.yale.edu |title=Yale Center for Molecular Discovery |website=Ycmd.yale.edu |date= |accessdate=2016-05-05}}</ref> His research interests focus on [[Chemical Biology]], particularly on controlled [[proteostasis]]. Crews has been a pioneer in the field of [[Proteolysis Targeting Chimera|Targeted Protein Degradation]] and his lab's research led to the development of the FDA approved anti-cancer drug [[Carfilzomib| Carfilzomib (Kyprolis®)]].<ref>{{cite web|url=http://cen.acs.org/articles/90/i35/Carfilzomib-Discovery-Drug.html |title=Carfilzomib: From Discovery To Drug &#124; August 27, 2012 Issue - Vol. 90 Issue 35 &#124; Chemical & Engineering News |website=Cen.acs.org |date=2012-08-27 |accessdate=2016-05-05}}</ref>
'''Craig M. Crews''', Ph.D. (born June 1, 1964) is an American scientist at Yale University. He is the John C. Malone Professor of [[molecular biology|Molecular, Cellular, and Developmental Biology]], and also holds joint appointments in the departments of [[Chemistry]] and [[Pharmacology]]. Crews is the Executive Director of the Yale Center for Molecular Discovery and a former Editor of [[Cell Chemical Biology]].<ref>{{cite web|url=http://www.cell.com/cell-chemical-biology/editors|title=Staff and Editorial Board|website=Cell Chemical Biology|accessdate= February 28, 2018}}</ref><ref>{{cite web|url=http://ycmd.yale.edu |title=Yale Center for Molecular Discovery |website=Ycmd.yale.edu |date= |accessdate=2016-05-05}}</ref> His research interests focus on [[Chemical Biology]], particularly on controlled [[proteostasis]]. Crews is a pioneer in the field of [[Proteolysis Targeting Chimera|Targeted Protein Degradation]] and his lab's research led to the development of the FDA approved anti-cancer drug [[Carfilzomib| Carfilzomib (Kyprolis®)]].<ref>{{cite web|url=http://cen.acs.org/articles/90/i35/Carfilzomib-Discovery-Drug.html |title=Carfilzomib: From Discovery To Drug &#124; August 27, 2012 Issue - Vol. 90 Issue 35 &#124; Chemical & Engineering News |website=Cen.acs.org |date=2012-08-27 |accessdate=2016-05-05}}</ref>


==Education and training==
==Education and training==
Crews graduated from the [[University of Virginia]] in 1986 with a bachelor's degree in Chemistry, after which he performed research at the [[University of Tübingen]] as a [[German Academic Exchange Service|German Academic Exchange Service (DAAD)]] Fellow. As a graduate student in the laboratory of [[Raymond L. Erikson|Raymond Erikson]] at [[Harvard University]], Crews purified and cloned the MAP kinase kinase [[Mitogen-activated protein kinase kinase|MEK1]],<ref>{{cite journal |vauthors=Crews CM, Alessandrini A, Erikson RL |title=The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product |journal=Science |volume=258 |issue=5081 |pages=478–80 |year=1992 |pmid=1411546 |doi=10.1126/science.1411546 |bibcode=1992Sci...258..478C }}</ref><ref>{{cite journal |vauthors=Crews CM, Erikson RL |title=Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=89 |issue=17 |pages=8205–9 |year=1992 |pmid=1381507 |pmc=49886 |doi=10.1073/pnas.89.17.8205|bibcode=1992PNAS...89.8205C }}</ref> a key kinase that controls cell growth. He subsequently worked in the research group of [[Stuart Schreiber]] as a [[Cancer Research Institute]] Fellow before joining the faculty of [[Yale University]] as an assistant professor in Molecular, Cellular, and Developmental Biology.
Crews graduated from the [[University of Virginia]] in 1986 with a bachelor's degree in Chemistry, after which he performed research at the [[University of Tübingen]] as a [[German Academic Exchange Service|German Academic Exchange Service (DAAD)]] Fellow.<ref name=":0">{{Cite web|title=Crews Laboratory|url=https://crewslab.yale.edu/biosketch.html|access-date=2021-08-20|website=crewslab.yale.edu|language=en}}</ref> As a graduate student in the laboratory of [[Raymond L. Erikson|Raymond Erikson]] at [[Harvard University]], Crews purified and cloned the MAP kinase kinase [[Mitogen-activated protein kinase kinase|MEK1]],<ref>{{cite journal |vauthors=Crews CM, Alessandrini A, Erikson RL |title=The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product |journal=Science |volume=258 |issue=5081 |pages=478–80 |year=1992 |pmid=1411546 |doi=10.1126/science.1411546 |bibcode=1992Sci...258..478C }}</ref><ref>{{cite journal |vauthors=Crews CM, Erikson RL |title=Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=89 |issue=17 |pages=8205–9 |year=1992 |pmid=1381507 |pmc=49886 |doi=10.1073/pnas.89.17.8205|bibcode=1992PNAS...89.8205C }}</ref> a key kinase that controls cell growth. He subsequently worked in the research group of [[Stuart Schreiber]] as a [[Cancer Research Institute]] Fellow before joining the faculty of [[Yale University]] as an assistant professor in Molecular, Cellular, and Developmental Biology in 1995.<ref name=":0" />


==Research==
==Research==
Crews studies controlled [[proteostasis]], i.e., the pharmacological modulation of protein turnover. In 2001, Crews developed (in collaboration with Ray Deshaies) PROTACs ([[Proteolysis Targeting Chimera]]s),<ref>{{cite web|title=PROTACs: A New Type of Drug That Can Target All Disease-Causing Proteins|url=http://scitechdaily.com/protacs-a-new-type-of-drug-that-can-target-all-disease-causing-proteins/|date=2015-06-11|publisher=SciTechDaily|accessdate=2016-05-22}}</ref><ref>{{cite web|title=Scientist wants to hijack cells' tiny garbage trucks to fight cancer|url=https://www.bostonglobe.com/business/2016/05/19/scientist-wants-hijack-cells-tiny-garbage-trucks-fight-cancer/zTINEWqETJ3gZEJfBjfFOO/story.html|date=2016-05-19|publisher=Boston Globe|accessdate=2016-05-22}}</ref> a new technology to induce [[proteolysis]]. PROTACs are dimeric molecules that recruit specific intracellular proteins to the cellular quality control machinery (i.e., an [[Ubiquitin ligase|E3 ubiquitin ligase]]) in a catalytic manner for subsequent removal by the proteasome.<ref>{{cite web|title=How Chemists Are Sending Bad Proteins Out With The Cellular Trash &#124; January 18, 2016 Issue - Vol. 94 Issue 3 &#124; Chemical & Engineering News|url=http://cen.acs.org/articles/94/i3/Chemists-Sending-Bad-Proteins-Cellular.html|date=2016-01-18|website=Cen.acs.org|accessdate=2016-05-05}}</ref> This technology has the potential to allow pharmacological targeting of proteins previously thought "undruggable" including many responsible for drug resistance in cancer.<ref>{{Cite journal|last1=Sun|first1=Xiuyun|last2=Gao|first2=Hongying|last3=Yang|first3=Yiqing|last4=He|first4=Ming|last5=Wu|first5=Yue|last6=Song|first6=Yugang|last7=Tong|first7=Yan|last8=Rao|first8=Yu|date=2019-12-24|title=PROTACs: great opportunities for academia and industry|journal=Signal Transduction and Targeted Therapy|language=en|volume=4|issue=1|page=64|doi=10.1038/s41392-019-0101-6|pmid=31885879|pmc=6927964|issn=2059-3635|doi-access=free}}</ref> The excitement around the field has resulted in private and public investment of more than $3.5 billion in therapeutic approaches based on targeted protein degradation.<ref>{{Cite web|title=With Over USD 3.5 Billion in Capital Investment, and Numerous High Value Licensing Deals, the Targeted Protein Degradation Market is Anticipated to Grow at an Annualized Rate of Over 30%, Claims Roots Analysis|url=https://www.prnewswire.com/news-releases/with-over-usd-3-5-billion-in-capital-investment-and-numerous-high-value-licensing-deals-the-targeted-protein-degradation-market-is-anticipated-to-grow-at-an-annualized-rate-of-over-30-claims-roots-analysis-301020745.html|last=Analysis|first=Roots|website=www.prnewswire.com|language=en|access-date=2020-05-12}}</ref> Prior to its work on PROTACs, the Crews lab’s synthesis and mode of action studies of the natural product [[epoxomicin]] revealed that it is a potent and selective [[proteasome inhibitor]].<ref>{{cite web|url=http://www.yalescientific.org/2012/11/carfilzomib-the-latest-triumph-of-targeted-therapies-development/ |title=Carfilzomib: The Latest Triumph of Targeted Therapies Development |publisher=Yale Scientific |date=2012-11-10 |accessdate=2016-05-22}}</ref> Subsequent [[medicinal chemistry]] efforts produced the epoxyketone containing proteasome inhibitor YU101,<ref>{{cite web|url=http://www.myelomacrowd.org/dr-craig-crews-crews-laboratory-yale-university-describes-discovery-development-carfilzomib-kyprolis-takes-get-new-drug-across-valley-death/|title=Dr. Craig Crews of the Crews Laboratory at Yale University describes his discovery and development of carfilzomib (Kyprolis) and what it takes to get a new drug across the "Valley of Death" - The Myeloma Crowd|date=12 September 2013|publisher=|accessdate=24 April 2018}}</ref> which served as the basis for the [[multiple myeloma]] drug [[Carfilzomib| Carfilzomib (Kyprolis®)]].
Crews studies controlled [[proteostasis]], i.e., the pharmacological modulation of protein turnover.<ref name=":1">{{Cite journal|last=Bond|first=Michael J.|last2=Crews M.|first2=Craig|date=2021|title=Proteolysis targeting chimeras (PROTACs) come of age: entering the third decade of targeted protein degradation|url=https://pubs.rsc.org/en/content/articlelanding/2021/cb/d1cb00011j|journal=RSC Chemical Biology|language=en|volume=2|issue=3|pages=725–742|doi=10.1039/D1CB00011J}}</ref> In 2001, Crews developed (in collaboration with Ray Deshaies) PROTACs ([[Proteolysis Targeting Chimera]]s),<ref>{{cite web|title=PROTACs: A New Type of Drug That Can Target All Disease-Causing Proteins|url=http://scitechdaily.com/protacs-a-new-type-of-drug-that-can-target-all-disease-causing-proteins/|date=2015-06-11|publisher=SciTechDaily|accessdate=2016-05-22}}</ref><ref>{{cite web|title=Scientist wants to hijack cells' tiny garbage trucks to fight cancer|url=https://www.bostonglobe.com/business/2016/05/19/scientist-wants-hijack-cells-tiny-garbage-trucks-fight-cancer/zTINEWqETJ3gZEJfBjfFOO/story.html|date=2016-05-19|publisher=Boston Globe|accessdate=2016-05-22}}</ref> a new technology to induce [[proteolysis]].<ref name=":1" /> PROTACs are dimeric molecules that recruit specific intracellular proteins to the cellular quality control machinery (i.e., an [[Ubiquitin ligase|E3 ubiquitin ligase]]) in a catalytic manner for subsequent removal by the proteasome.<ref>{{cite web|title=How Chemists Are Sending Bad Proteins Out With The Cellular Trash &#124; January 18, 2016 Issue - Vol. 94 Issue 3 &#124; Chemical & Engineering News|url=http://cen.acs.org/articles/94/i3/Chemists-Sending-Bad-Proteins-Cellular.html|date=2016-01-18|website=Cen.acs.org|accessdate=2016-05-05}}</ref> This technology has the potential to allow pharmacological targeting of proteins previously thought "undruggable" including many responsible for drug resistance in cancer.<ref>{{Cite journal|last1=Sun|first1=Xiuyun|last2=Gao|first2=Hongying|last3=Yang|first3=Yiqing|last4=He|first4=Ming|last5=Wu|first5=Yue|last6=Song|first6=Yugang|last7=Tong|first7=Yan|last8=Rao|first8=Yu|date=2019-12-24|title=PROTACs: great opportunities for academia and industry|journal=Signal Transduction and Targeted Therapy|language=en|volume=4|issue=1|page=64|doi=10.1038/s41392-019-0101-6|pmid=31885879|pmc=6927964|issn=2059-3635|doi-access=free}}</ref> Excitement around the field has resulted in much private and public investment in therapeutic approaches based on targeted protein degradation.<ref>{{Cite web|title=With Over USD 3.5 Billion in Capital Investment, and Numerous High Value Licensing Deals, the Targeted Protein Degradation Market is Anticipated to Grow at an Annualized Rate of Over 30%, Claims Roots Analysis|url=https://www.prnewswire.com/news-releases/with-over-usd-3-5-billion-in-capital-investment-and-numerous-high-value-licensing-deals-the-targeted-protein-degradation-market-is-anticipated-to-grow-at-an-annualized-rate-of-over-30-claims-roots-analysis-301020745.html|last=Analysis|first=Roots|website=www.prnewswire.com|language=en|access-date=2020-05-12}}</ref> Prior to its work on PROTACs, the Crews lab’s synthesis and mode of action studies of the natural product [[epoxomicin]] revealed that it is a potent and selective [[proteasome inhibitor]].<ref>{{cite web|url=http://www.yalescientific.org/2012/11/carfilzomib-the-latest-triumph-of-targeted-therapies-development/ |title=Carfilzomib: The Latest Triumph of Targeted Therapies Development |publisher=Yale Scientific |date=2012-11-10 |accessdate=2016-05-22}}</ref> Subsequent [[medicinal chemistry]] efforts produced the epoxyketone containing proteasome inhibitor YU101,<ref>{{cite web|url=http://www.myelomacrowd.org/dr-craig-crews-crews-laboratory-yale-university-describes-discovery-development-carfilzomib-kyprolis-takes-get-new-drug-across-valley-death/|title=Dr. Craig Crews of the Crews Laboratory at Yale University describes his discovery and development of carfilzomib (Kyprolis) and what it takes to get a new drug across the "Valley of Death" - The Myeloma Crowd|date=12 September 2013|publisher=|accessdate=24 April 2018}}</ref> which served as the basis for the [[multiple myeloma]] drug [[Carfilzomib| Carfilzomib (Kyprolis®)]].<ref>{{Cite web|last=Crowd|first=The Myeloma|title=Dr. Craig Crews of the Crews Laboratory at Yale University describes his discovery and development of carfilzomib (Kyprolis) and what it takes to get a new drug across the finish line in myeloma.|url=https://www.myelomacrowd.org/dr-craig-crews-crews-laboratory-yale-university-describes-discovery-development-carfilzomib-kyprolis-takes-get-new-drug-across-valley-death/|access-date=2021-08-20|website=www.myelomacrowd.org|language=en}}</ref><ref>{{Cite web|title=Craig Crews, PhD|url=https://medicine.yale.edu/profile/craig_crews/|access-date=2021-08-20|website=medicine.yale.edu|language=en}}</ref>


==[[Arvinas]]==
==Arvinas==
In 2013, Crews founded [[New Haven, Connecticut|New Haven]]-based [[Arvinas]], which uses the [[Proteolysis Targeting Chimera|PROTAC]] protein degradation technology from his lab to develop drugs to treat cancer, neurodegeneration, and other diseases. In 2015, Arvinas partnered with [[Merck & Co.|Merck]]<ref>{{cite web|title=Merck wagers $434M on Arvinas and its protein-disposal system|url=http://www.fiercebiotech.com/partnering/merck-wagers-434m-on-arvinas-and-its-protein-disposal-system|date=|publisher=FierceBiotech|accessdate=2016-05-05}}</ref> and [[Genentech]]<ref>{{cite web|title=Genentech embraces Arvinas with $300M tie-up on protein degradation|url=http://www.fiercebiotech.com/biotech/genentech-embraces-arvinas-300m-tie-up-on-protein-degradation|date=|publisher=FierceBiotech|accessdate=2016-05-05}}</ref> to develop PROTAC-based drugs. In 2018, Arvinas signed a $830M plus deal with [[Pfizer]].<ref>{{cite web|title=Arvinas in $830M-plus Pfizer biobucks deal|url=https://www.fiercebiotech.com/biotech/arvinas-830m-plus-pfizer-biobucks-deal|date=|publisher=FierceBiotech|accessdate=2018-01-04}}</ref> On 1 Oct 2019, [[Bayer]] and Arvinas announced that they had finalized the terms of their agreement to jointly launch a new company, Oerth Bio, with John Dombrosky as its chief executive officer. Oerth Bio leverages Arvinas’ expertise in targeted protein degradation and Bayer’s decades of experience in developing both human therapies and innovative, sustainable agricultural technologies.<ref>{{Cite web|title=Bayer and Arvinas Unveil Targeted Protein Degradation Joint Venture, Oerth Bio|url=https://ir.arvinas.com/news-releases/news-release-details/bayer-and-arvinas-unveil-targeted-protein-degradation-joint|website=Arvinas|language=en|access-date=2020-02-14}}</ref> On 23 October 2019, Arvinas presented initial safety, tolerability, and pharmacokinetic data from the company’s ongoing Phase 1 clinical trials of two orally bioavailable PROTACs, targeting the [[Androgen Receptor]] (ARV-110) and the [[Estrogen Receptor]] (ARV-471).<ref>{{Cite web|title=Arvinas Presents a Platform Update, Including Initial Data from the First Two Clinical Trials of PROTAC® Targeted Protein Degraders|url=https://ir.arvinas.com/news-releases/news-release-details/arvinas-presents-platform-update-including-initial-data-first|website=Arvinas|language=en|access-date=2020-05-12}}</ref> Both drugs appeared to be well tolerated and no dose-limiting toxicities or grade 2, 3 or 4 adverse events were observed.<ref>{{Cite journal|last=Mullard|first=Asher|date=2019-11-06|title=Arvinas's PROTACs pass first safety and PK analysis|url=https://www.nature.com/articles/d41573-019-00188-4|journal=Nature Reviews Drug Discovery|language=en|volume=18|issue=12|pages=895|doi=10.1038/d41573-019-00188-4|pmid=31780851|s2cid=208357723}}</ref> Further updates are expected at the [[American Society of Clinical Oncology|ASCO]] Annual Meeting in 2020.
In 2013, Crews founded [[New Haven, Connecticut|New Haven]]-based Arvinas, which uses the [[Proteolysis Targeting Chimera|PROTAC]] protein degradation technology from his lab to develop drugs to treat cancer, neurodegeneration, and other diseases. In 2019, Arvinas presented initial safety, tolerability, and pharmacokinetic data from the company’s ongoing Phase 1 clinical trials of two orally bioavailable PROTACs, targeting the Androgen Receptor (ARV-110) and the Estrogen Receptor (ARV-471).<ref>{{Cite web|title=Arvinas Presents a Platform Update, Including Initial Data from the First Two Clinical Trials of PROTAC® Targeted Protein Degraders|url=https://ir.arvinas.com/news-releases/news-release-details/arvinas-presents-platform-update-including-initial-data-first|website=Arvinas|language=en|access-date=2020-05-12}}</ref> Both drugs appeared to be well tolerated and no dose-limiting toxicities or grade 2, 3 or 4 adverse events were observed.<ref>{{Cite journal|last=Mullard|first=Asher|date=2019-11-06|title=Arvinas's PROTACs pass first safety and PK analysis|url=https://www.nature.com/articles/d41573-019-00188-4|journal=Nature Reviews Drug Discovery|language=en|volume=18|issue=12|pages=895|doi=10.1038/d41573-019-00188-4|pmid=31780851|s2cid=208357723}}</ref> Moreover, ongoing clinical trials have demonstrated evidence of efficacy, e.g., target protein level reduction and tumor shrinkage in some patients.<ref>{{Cite web|title=Pfizer Strengthens Cancer Standing with Protein Degrader Collaboration|url=https://www.biospace.com/article/pfizer-strikes-another-deal-with-protein-degrader-arvinas-/|access-date=2021-08-20|website=BioSpace|language=en-US}}</ref><ref>{{Cite web|last=Houlton2021-07-30T14:27:00+01:00|first=Sarah|title=Pfizer backs protein degrader drugs with Arvinas deal|url=https://www.chemistryworld.com/news/pfizer-backs-protein-degrader-drugs-with-arvinas-deal/4014086.article|access-date=2021-08-20|website=Chemistry World|language=en}}</ref>


==Proteolix==
==Proteolix==
In 2003, Crews co-founded the biotechnology company [[Proteolix]] to develop YU101, the next generation [[proteasome inhibitor]] from his lab, which ultimately became [[carfilzomib]]. Marketed under the trade name Kyprolis, [[carfilzomib]] was approved by the FDA on June 20, 2012 for use in patients with multiple myeloma who have received at least two prior therapies and have demonstrated disease progression on or within 60 days of completion of the last therapy.<ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312920.htm |title=FDA approves Kyprolis for some patients with multiple myeloma |website=Fda.gov |date=2012-07-20 |accessdate=2016-05-05}}</ref> Based on successful Phase II trials of [[carfilzomib]], [[Onyx Pharmaceuticals]] acquired Proteolix in 2009 <ref>{{cite web|url=http://www.fiercebiotech.com/biotech/onyx-strikes-851m-deal-to-buy-proteolix |title=Onyx strikes $851M deal to buy Proteolix |publisher=FierceBiotech |date= |accessdate=2016-05-05}}</ref> and was itself acquired by Amgen in 2013 for $10.4 billion.<ref>{{cite web|author=Kevin McCaffrey |url=http://www.mmm-online.com/channel/kyprolis-growth-prospects-at-center-of-amgen-onyx-deal/article/308935/ |title=Kyprolis growth prospects at center of Amgen-Onyx deal - Medical Marketing and Media |website=Mmm-online.com |date= |accessdate=2016-05-05}}</ref>
In 2003, Crews co-founded the biotechnology company [[Proteolix]] to develop YU101, the next generation [[proteasome inhibitor]] from his lab, which ultimately became [[carfilzomib]]. Marketed under the trade name [[Carfilzomib|Kyprolis®]], [[carfilzomib]] was approved by the FDA on June 20, 2012 for use in patients with multiple myeloma.<ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312920.htm |title=FDA approves Kyprolis for some patients with multiple myeloma |website=Fda.gov |date=2012-07-20 |accessdate=2016-05-05}}</ref> Based on successful Phase II trials of [[carfilzomib]], [[Onyx Pharmaceuticals]] acquired Proteolix in 2009 <ref>{{cite web|url=http://www.fiercebiotech.com/biotech/onyx-strikes-851m-deal-to-buy-proteolix |title=Onyx strikes $851M deal to buy Proteolix |publisher=FierceBiotech |date= |accessdate=2016-05-05}}</ref> and was itself acquired by Amgen in 2013.<ref>{{cite web|author=Kevin McCaffrey |url=http://www.mmm-online.com/channel/kyprolis-growth-prospects-at-center-of-amgen-onyx-deal/article/308935/ |title=Kyprolis growth prospects at center of Amgen-Onyx deal - Medical Marketing and Media |website=Mmm-online.com |date= |accessdate=2016-05-05}}</ref>


==Awards and recognition==
==Awards and recognition==
*2021: [[Honorary doctoral degree|Honorary Doctoral Degree]], [[Technische Universität Dortmund|Technische Universität Dortmund, Germany]] (doctor rerum naturalium honoris causa)<ref name=":0" />
*2020: Swedish Pharmaceutical Society [[Scheele Award]]<ref>{{Cite web|title=Awards & Honors|url=https://www.yalecancercenter.org/research/excellence/awards/|access-date=2021-08-20|website=www.yalecancercenter.org|language=en}}</ref>
*2020: Boehringer Ingelheim Foundation [[Heinrich Wieland Prize]]<ref>{{Cite web|title=2020: Professor Dr Craig M. Crews - Heinrich Wieland Prize - Homepage|url=https://www.heinrich-wieland-prize.de/laureates/since-2020/articles/id-2020-professor-dr-craig-m-crews.html#:~:text=Research-,Craig%20M.,protein%20degradation%20machinery,%20the%20proteasome.|access-date=2021-08-20|website=www.heinrich-wieland-prize.de}}</ref>
*2019: Pharmacia-ASPET Award for Experimental Therapeutics<ref>{{Cite web|title=2019 Award Winners|url=https://www.aspet.org/aspet/meetings-awards/aspet-awards/aspet-scientific-achievement-awards/aspet-award-winners/2019-award-winners|access-date=2021-08-20|website=Default|language=en}}</ref>
*2018: Pierre Fabre Award <ref>https://www.rict2018.org/speakers{{Dead link|date=July 2020 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
*2018: Pierre Fabre Award <ref>https://www.rict2018.org/speakers{{Dead link|date=July 2020 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
*2018: [[Royal Society of Chemistry]] Khorana Prize <ref>{{cite web|url=http://www.rsc.org/ScienceAndTechnology/Awards/KhoranaPrize/2018-Winner.asp|title=RSC Khorana Prize 2018 Winner|date=2018-05-08|accessdate=2018-06-01}}</ref>
*2018: [[Royal Society of Chemistry]] Khorana Prize <ref>{{cite web|url=http://www.rsc.org/ScienceAndTechnology/Awards/KhoranaPrize/2018-Winner.asp|title=RSC Khorana Prize 2018 Winner|date=2018-05-08|accessdate=2018-06-01}}</ref>
*2017: [[American Association for Cancer Research|AACR]] Award for Outstanding Achievement in Chemistry in Cancer Research<ref>{{cite web|url=http://news.yale.edu/yale-s-craig-crews-recipient-cancer-research-award|title=Yale's Craig Crews is recipient of cancer research award |date=2017-02-28 |accessdate=2017-03-05}}</ref>
*2017: [[American Association for Cancer Research|AACR]] Award for Outstanding Achievement in Chemistry in Cancer Research<ref>{{cite web|url=http://news.yale.edu/yale-s-craig-crews-recipient-cancer-research-award|title=Yale's Craig Crews is recipient of cancer research award |date=2017-02-28 |accessdate=2017-03-05}}</ref>
*2015: Inaugural Recipient of the [[National Cancer Institute]] Outstanding Investigator Award (R35)<ref>{{cite web|url=https://medicine.yale.edu/news/article.aspx?id=11339 |title=Craig Crews, PhD, receives NCI's Outstanding Investigator Award |date=2015-10-16 |accessdate=2016-05-22}}</ref>
*2015: Inaugural Recipient of the [[National Cancer Institute]] Outstanding Investigator Award (R35)<ref>{{cite web|url=https://medicine.yale.edu/news/article.aspx?id=11339 |title=Craig Crews, PhD, receives NCI's Outstanding Investigator Award |date=2015-10-16 |accessdate=2016-05-22}}</ref>
*2015: [[Yale Cancer Center]] Translational Research Prize<ref>{{cite web|url=http://medicine.yale.edu/news/article.aspx?id=11759 |title=Craig M. Crews, PhD receives the Yale Cancer Center Translational Research Prize |date=2015-11-25 |accessdate=2016-05-22}}</ref>
*2014: UCB-Ehrlich Award for Excellence in Medicinal Chemistry<ref>{{cite web|url=http://news.yale.edu/crews-awarded-ucb-ehrlich-award-work-anti-cancer-therapy |title=YaleNews &#124; Crews awarded UCB-Ehrlich Award for work on anti-cancer therapy |website=News.yale.edu |date=2014-08-18 |accessdate=2016-05-05}}</ref>

*2014: UCB-Ehrlich Award for Excellence in Medicinal Chemistry (European Federation of Medicinal Chemistry)<ref>{{cite web|url=http://news.yale.edu/crews-awarded-ucb-ehrlich-award-work-anti-cancer-therapy |title=YaleNews &#124; Crews awarded UCB-Ehrlich Award for work on anti-cancer therapy |website=News.yale.edu |date=2014-08-18 |accessdate=2016-05-05}}</ref>
== Publications ==
*2013: Entrepreneur of the Year, Connecticut United for Research Excellence (CURE)<ref>{{cite web |url=http://cureconnect.org/events/cure-entrepreneur-of-the-year/ |title=CURE Entrepreneur of the Year Award – CURE :: Connecticut's Bioscience Innovation Network |website=Cureconnect.org |date=2014-06-20 |accessdate=2016-05-05 |archive-url=https://web.archive.org/web/20160428092716/http://cureconnect.org/events/cure-entrepreneur-of-the-year/ |archive-date=2016-04-28 |url-status=dead }}</ref>

*2013: [[Fellow of the American Association for the Advancement of Science|Fellow, American Association for the Advancement of Science]]<ref>{{cite web|last=Dodson |first=Helen |url=http://news.yale.edu/2013/12/02/yale-faculty-elected-world-s-largest-scientific-society |title=YaleNews &#124; Yale faculty elected to world's largest scientific society |website=News.yale.edu |date=2013-12-02 |accessdate=2016-05-05}}</ref>
* Bond M, Chu L, Nalawansha D, Li K, Crews CM. Targeted Degradation of Oncogenic KRAS<sup>G12C</sup> by VHL-recruiting PROTACs. ''[[ACS Central Science]],'' 6(8):1367–1375.<ref>{{Cite journal|last=Bond|first=Michael J.|last2=Chu|first2=Ling|last3=Nalawansha|first3=Dhanusha A.|last4=Li|first4=Ke|last5=Crews|first5=Craig M.|date=2020-08-26|title=Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs|url=https://doi.org/10.1021/acscentsci.0c00411|journal=ACS Central Science|volume=6|issue=8|pages=1367–1375|doi=10.1021/acscentsci.0c00411|issn=2374-7943|pmc=PMC7453568|pmid=32875077}}</ref>
*2011: Senior Scholar Award, [[Ellison Medical Foundation]]<ref>{{cite web |url=http://www.ellisonfoundation.org/awardlist?page=1 |title=2011 Senior Scholar Award In Aging |website=Ellisonfoundation.org |access-date=2016-05-05 |url-status=dead |archive-url=https://web.archive.org/web/20160513154119/http://www.ellisonfoundation.org/awardlist?page=1 |archive-date=2016-05-13 |df= }}</ref>
* Cromm PM, Samarasinghe KTG, Hines J, Crews CM Addressing Kinase-independent Functions of FAK via PROTAC-mediated Degradation. ''J American Chemical Society'' 140(49): 17026-17026.<ref>{{Cite journal|last=Cromm|first=Philipp M.|last2=Samarasinghe|first2=Kusal T. G.|last3=Hines|first3=John|last4=Crews|first4=Craig M.|date=2018-12-12|title=Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation|url=https://doi.org/10.1021/jacs.8b08008|journal=Journal of the American Chemical Society|volume=140|issue=49|pages=17019–17026|doi=10.1021/jacs.8b08008|issn=0002-7863}}</ref>
*2010-2013: Visiting Professor, [[University of Konstanz|Universität Konstanz]], Germany
* Burslem GM, Smith BE, Lai A, Jaime-Figueroa S, McQuaid D, Bondeson DP, Toure M, Dong H, Qian Y, Wang J, Crew AP, Hines J, Crews CM. The advantages of targeted protein degradation over inhibition: a RTK case study. ''[[Cell Chemical Biology]]'' 25:67-77.<ref>{{Cite journal|last=Burslem|first=George M.|last2=Smith|first2=Blake E.|last3=Lai|first3=Ashton C.|last4=Jaime-Figueroa|first4=Saul|last5=McQuaid|first5=Daniel C.|last6=Bondeson|first6=Daniel P.|last7=Toure|first7=Momar|last8=Dong|first8=Hanqing|last9=Qian|first9=Yimin|last10=Wang|first10=Jing|last11=Crew|first11=Andrew P.|date=2018-01-18|title=The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study|url=https://pubmed.ncbi.nlm.nih.gov/29129716/|journal=Cell Chemical Biology|volume=25|issue=1|pages=67–77.e3|doi=10.1016/j.chembiol.2017.09.009|issn=2451-9448|pmc=5831399|pmid=29129716}}</ref>
*2009: [[Grand Challenges In Global Health|Gates Foundation Global Grand Challenge Explorations Grant]]<ref>{{cite web|url=http://www.rsc.org/chemistryworld/News/2011/January/06011102.asp|title=Using HIV against itself|publisher=|accessdate=24 April 2018}}</ref>
* Salami J and Crews CM. Waste Disposal- An attractive strategy for cancer therapy ''Science'' 355(6330):1163-1167.<ref>{{Cite journal|last=Salami|first=Jemilat|last2=Crews|first2=Craig M.|date=2017-03-17|title=Waste disposal-An attractive strategy for cancer therapy|url=https://pubmed.ncbi.nlm.nih.gov/28302825/|journal=Science (New York, N.Y.)|volume=355|issue=6330|pages=1163–1167|doi=10.1126/science.aam7340|issn=1095-9203|pmid=28302825}}</ref>
*2005: Friedrich Wilhelm Bessel Research Award, [[Alexander von Humboldt Foundation]]<ref>{{cite web|last=Zagorski |first=Nick |url=http://www.asbmb.org/asbmbtoday/asbmbtoday_article.aspx?id=7286 |title=The Humboldt Foundation |website=Asbmb.org |date= |accessdate=2016-05-05}}</ref>
* Bondeson DP, Mares A, Smith IED, Ko E, Campos S, Miah AH, Mulholland KE, Routly N, Buckley DL, Gustafson JL, Zinn N, Grandi P, Shimamura S, Bergamini G, Faelth-Savitski M, Bantscheff M, Cox C, Gordon DA, Willard RR, Flanagan JJ, Casillas LN, Votta BJ, den Besten W, Famm K, Sruidenier L, Carter PS, Harling JD, Churcher I, Crews CM. Catalytic ''in vivo'' protein knockdown by small-molecule PROTACs. ''[[Nature Chemical Biology]]'' 2015 11(8):611-7.<ref>{{Cite journal|last=Bondeson|first=Daniel P|last2=Mares|first2=Alina|last3=Smith|first3=Ian E D|last4=Ko|first4=Eunhwa|last5=Campos|first5=Sebastien|last6=Miah|first6=Afjal H|last7=Mulholland|first7=Katie E|last8=Routly|first8=Natasha|last9=Buckley|first9=Dennis L|last10=Gustafson|first10=Jeffrey L|last11=Zinn|first11=Nico|date=|title=Catalytic in vivo protein knockdown by small-molecule PROTACs|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629852/|journal=Nature chemical biology|volume=11|issue=8|pages=611–617|doi=10.1038/nchembio.1858|issn=1552-4450|pmc=4629852|pmid=26075522}}</ref>
*2005: Fellow of the [[Royal Society of Chemistry]]
* Lai, AC, Toure, M, Hellerschmied, D, Salami, J, Jaime-Figueroa, S, Ko, E, Hines, J, Crews, CM. Accessing oncogenic BCR-ABL for degradation by modular PROTAC design. ''[[Angewandte Chemie International|Angewandte Chemie Int.]] Ed. Engl.'' 55:807–810.<ref>{{Cite journal|last=Lai|first=Ashton C.|last2=Toure|first2=Momar|last3=Hellerschmied|first3=Doris|last4=Salami|first4=Jemilat|last5=Jaime-Figueroa|first5=Saul|last6=Ko|first6=Eunhwa|last7=Hines|first7=John|last8=Crews|first8=Craig M.|date=2016-01-11|title=Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL|url=https://pubmed.ncbi.nlm.nih.gov/26593377/|journal=Angewandte Chemie (International Ed. in English)|volume=55|issue=2|pages=807–810|doi=10.1002/anie.201507634|issn=1521-3773|pmc=4733637|pmid=26593377}}</ref>
*2002: [[Prostate Cancer Foundation|CaP CURE]] Research Award <ref>http://www.mikemilken.com/pdfs/pcf_annual_2003.pdf</ref>
* Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae H-S, Sundberg TB, Crews CM. Making the problem go away: Targeted androgen receptor degradation overcomes resistance to prostate cancer therapy. ''[[Angewandte Chemie International|Angewandte Chemie Int.]] Ed. Engl''. 2015 Aug 10;54(33):9659-62.<ref>{{Cite journal|last=Gustafson|first=Jeffrey L.|last2=Neklesa|first2=Taavi K.|last3=Cox|first3=Carly S.|last4=Roth|first4=Anke G.|last5=Buckley|first5=Dennis L.|last6=Tae|first6=Hyun Seop|last7=Sundberg|first7=Thomas B.|last8=Stagg|first8=D. Blake|last9=Hines|first9=John|last10=McDonnell|first10=Donald P.|last11=Norris|first11=John D.|date=2015-08-10|title=Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging|url=https://pubmed.ncbi.nlm.nih.gov/26083457/|journal=Angewandte Chemie (International Ed. in English)|volume=54|issue=33|pages=9659–9662|doi=10.1002/anie.201503720|issn=1521-3773|pmc=4547777|pmid=26083457}}</ref>
*1996: [[Burroughs Wellcome Fund]] New Investigator Award<ref>{{cite web|url=http://www.bwfund.org/awards-and-accolades-july-2009 |title=Awards and Accolades - July 2009 &#124; Burroughs Wellcome Fund |website=Bwfund.org |date= |accessdate=2016-05-05}}</ref>
* Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Himes J, Winkler JD, Crew AP, Coleman K, Crews CM. Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. ''[[Chemistry & Biology]]'' 22:1-9.<ref>{{Cite journal|last=Lu|first=Jing|last2=Qian|first2=Yimin|last3=Altieri|first3=Martha|last4=Dong|first4=Hanqing|last5=Wang|first5=Jing|last6=Raina|first6=Kanak|last7=Hines|first7=John|last8=Winkler|first8=James|last9=Crew|first9=Andrew|last10=Coleman|first10=Kevin|last11=Crews|first11=Craig|date=2015-06-18|title=Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4|url=https://pubmed.ncbi.nlm.nih.gov/26051217/|journal=Chemistry and Biology|volume=22|issue=6|pages=755–763|doi=10.1016/j.chembiol.2015.05.009|issn=1879-1301|pmc=4475452|pmid=26051217}}</ref>
*1986: German Academic Exchange Service Fellow (DAAD)
* Buckley DL, Van Molle I, Gareiss PC, Tae H-S, Michel J, Noblin DJ, Jorgensen WL, Ciulli A, and CM Crews. Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1alpha interaction. ''J American Chemical Society'' 134(10):4465-8.<ref>{{Cite journal|last=Buckley|first=Dennis L.|last2=Van Molle|first2=Inge|last3=Gareiss|first3=Peter C.|last4=Tae|first4=Hyun Seop|last5=Michel|first5=Julien|last6=Noblin|first6=Devin J.|last7=Jorgensen|first7=William L.|last8=Ciulli|first8=Alessio|last9=Crews|first9=Craig M.|date=2012-03-14|title=Targeting the von Hippel–Lindau E3 Ubiquitin Ligase Using Small Molecules To Disrupt the VHL/HIF-1α Interaction|url=https://doi.org/10.1021/ja209924v|journal=Journal of the American Chemical Society|volume=134|issue=10|pages=4465–4468|doi=10.1021/ja209924v|issn=0002-7863|pmc=PMC3448299|pmid=22369643}}</ref>
* Schneekloth Jr., JS, F Fonseca, M Koldobskiy, A Mandal, R Deshaies, K Sakamoto, and CM Crews. Chemical genetic control of protein levels: Selective ''in vivo'' targeted degradation ''J American Chemical Society'' 126(12):3748-54.<ref>{{Cite journal|last=Schneekloth|first=John S.|last2=Fonseca|first2=Fabiana N.|last3=Koldobskiy|first3=Michael|last4=Mandal|first4=Amit|last5=Deshaies|first5=Raymond|last6=Sakamoto|first6=Kathleen|last7=Crews|first7=Craig M.|date=|title=Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation|url=https://pubs.acs.org/doi/pdf/10.1021/ja039025z|journal=Journal of the American Chemical Society|volume=126|issue=12|pages=3748–3754|doi=10.1021/ja039025z|issn=0002-7863}}</ref>
* Sakamoto KM, KB Kim, A Kumagai, F Mercurio, CM Crews, and RJ Deshaies. PROTACs: Chimeric Molecules that Target Proteins to the Skp1-Cullin-F Box Complex for Ubiquitination and Degradation, ''Proc. Natl. Acad. Sci. USA'' 98:8554-8559.<ref>{{Cite web|title=(PDF) Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation|url=https://www.researchgate.net/publication/11901886_Protacs_Chimeric_molecules_that_target_proteins_to_the_Skp1-Cullin-F_box_complex_for_ubiquitination_and_degradation|access-date=2021-08-20|website=ResearchGate|language=en}}</ref>
* Crews CM, AA Alessandrini, and RL Erikson. The primary structure of MEK, a protein kinase that phosphorylates and activates the ERK gene product. ''Science'', 258:478-480.<ref>{{Cite web|title=Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation|url=https://www.researchgate.net/publication/11901886_Protacs_Chimeric_molecules_that_target_proteins_to_the_Skp1-Cullin-F_box_complex_for_ubiquitination_and_degradation|access-date=1 August 2001|website=www.researchgate.net}}</ref>


==References==
==References==
{{Reflist|30em}}
{{Reflist}}


==External links==
==External links==

Revision as of 08:50, 20 August 2021

Craig M. Crews
File:Craig Crews.jpg
BornJune 1, 1964 (1964-06) (age 60)
Alma materUniversity of Virginia
Harvard University
Known forProteolysis Targeting Chimeras (PROTACs)
Controlled Proteostasis
Carfilzomib
AwardsFriedrich Wilhelm Bessel Research Award (Alexander von Humboldt Foundation) (2005)
UCB-Ehrlich Award for Excellence in Medicinal Chemistry (2014)
National Cancer Institute Outstanding Investigator Award (2015)
AACR Award for Outstanding Achievement in Chemistry in Cancer Research (2017)
Pierre Fabre Award (2018)
RSC Khorana Prize (2018)
Scientific career
FieldsChemical Biology
InstitutionsYale University
Doctoral advisorsRaymond L. Erikson
Stuart Schreiber (Postdoctoral Advisor)

Craig M. Crews, Ph.D. (born June 1, 1964) is an American scientist at Yale University. He is the John C. Malone Professor of Molecular, Cellular, and Developmental Biology, and also holds joint appointments in the departments of Chemistry and Pharmacology. Crews is the Executive Director of the Yale Center for Molecular Discovery and a former Editor of Cell Chemical Biology.[1][2] His research interests focus on Chemical Biology, particularly on controlled proteostasis. Crews is a pioneer in the field of Targeted Protein Degradation and his lab's research led to the development of the FDA approved anti-cancer drug Carfilzomib (Kyprolis®).[3]

Education and training

Crews graduated from the University of Virginia in 1986 with a bachelor's degree in Chemistry, after which he performed research at the University of Tübingen as a German Academic Exchange Service (DAAD) Fellow.[4] As a graduate student in the laboratory of Raymond Erikson at Harvard University, Crews purified and cloned the MAP kinase kinase MEK1,[5][6] a key kinase that controls cell growth. He subsequently worked in the research group of Stuart Schreiber as a Cancer Research Institute Fellow before joining the faculty of Yale University as an assistant professor in Molecular, Cellular, and Developmental Biology in 1995.[4]

Research

Crews studies controlled proteostasis, i.e., the pharmacological modulation of protein turnover.[7] In 2001, Crews developed (in collaboration with Ray Deshaies) PROTACs (Proteolysis Targeting Chimeras),[8][9] a new technology to induce proteolysis.[7] PROTACs are dimeric molecules that recruit specific intracellular proteins to the cellular quality control machinery (i.e., an E3 ubiquitin ligase) in a catalytic manner for subsequent removal by the proteasome.[10] This technology has the potential to allow pharmacological targeting of proteins previously thought "undruggable" including many responsible for drug resistance in cancer.[11] Excitement around the field has resulted in much private and public investment in therapeutic approaches based on targeted protein degradation.[12] Prior to its work on PROTACs, the Crews lab’s synthesis and mode of action studies of the natural product epoxomicin revealed that it is a potent and selective proteasome inhibitor.[13] Subsequent medicinal chemistry efforts produced the epoxyketone containing proteasome inhibitor YU101,[14] which served as the basis for the multiple myeloma drug Carfilzomib (Kyprolis®).[15][16]

Arvinas

In 2013, Crews founded New Haven-based Arvinas, which uses the PROTAC protein degradation technology from his lab to develop drugs to treat cancer, neurodegeneration, and other diseases. In 2019, Arvinas presented initial safety, tolerability, and pharmacokinetic data from the company’s ongoing Phase 1 clinical trials of two orally bioavailable PROTACs, targeting the Androgen Receptor (ARV-110) and the Estrogen Receptor (ARV-471).[17] Both drugs appeared to be well tolerated and no dose-limiting toxicities or grade 2, 3 or 4 adverse events were observed.[18] Moreover, ongoing clinical trials have demonstrated evidence of efficacy, e.g., target protein level reduction and tumor shrinkage in some patients.[19][20]

Proteolix

In 2003, Crews co-founded the biotechnology company Proteolix to develop YU101, the next generation proteasome inhibitor from his lab, which ultimately became carfilzomib. Marketed under the trade name Kyprolis®, carfilzomib was approved by the FDA on June 20, 2012 for use in patients with multiple myeloma.[21] Based on successful Phase II trials of carfilzomib, Onyx Pharmaceuticals acquired Proteolix in 2009 [22] and was itself acquired by Amgen in 2013.[23]

Awards and recognition

Publications

  • Bond M, Chu L, Nalawansha D, Li K, Crews CM. Targeted Degradation of Oncogenic KRASG12C by VHL-recruiting PROTACs. ACS Central Science, 6(8):1367–1375.[32]
  • Cromm PM, Samarasinghe KTG, Hines J, Crews CM Addressing Kinase-independent Functions of FAK via PROTAC-mediated Degradation. J American Chemical Society 140(49): 17026-17026.[33]
  • Burslem GM, Smith BE, Lai A, Jaime-Figueroa S, McQuaid D, Bondeson DP, Toure M, Dong H, Qian Y, Wang J, Crew AP, Hines J, Crews CM. The advantages of targeted protein degradation over inhibition: a RTK case study. Cell Chemical Biology 25:67-77.[34]
  • Salami J and Crews CM. Waste Disposal- An attractive strategy for cancer therapy Science 355(6330):1163-1167.[35]
  • Bondeson DP, Mares A, Smith IED, Ko E, Campos S, Miah AH, Mulholland KE, Routly N, Buckley DL, Gustafson JL, Zinn N, Grandi P, Shimamura S, Bergamini G, Faelth-Savitski M, Bantscheff M, Cox C, Gordon DA, Willard RR, Flanagan JJ, Casillas LN, Votta BJ, den Besten W, Famm K, Sruidenier L, Carter PS, Harling JD, Churcher I, Crews CM. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nature Chemical Biology 2015 11(8):611-7.[36]
  • Lai, AC, Toure, M, Hellerschmied, D, Salami, J, Jaime-Figueroa, S, Ko, E, Hines, J, Crews, CM. Accessing oncogenic BCR-ABL for degradation by modular PROTAC design. Angewandte Chemie Int. Ed. Engl. 55:807–810.[37]
  • Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae H-S, Sundberg TB, Crews CM. Making the problem go away: Targeted androgen receptor degradation overcomes resistance to prostate cancer therapy. Angewandte Chemie Int. Ed. Engl. 2015 Aug 10;54(33):9659-62.[38]
  • Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Himes J, Winkler JD, Crew AP, Coleman K, Crews CM. Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. Chemistry & Biology 22:1-9.[39]
  • Buckley DL, Van Molle I, Gareiss PC, Tae H-S, Michel J, Noblin DJ, Jorgensen WL, Ciulli A, and CM Crews. Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1alpha interaction. J American Chemical Society 134(10):4465-8.[40]
  • Schneekloth Jr., JS, F Fonseca, M Koldobskiy, A Mandal, R Deshaies, K Sakamoto, and CM Crews. Chemical genetic control of protein levels: Selective in vivo targeted degradation J American Chemical Society 126(12):3748-54.[41]
  • Sakamoto KM, KB Kim, A Kumagai, F Mercurio, CM Crews, and RJ Deshaies. PROTACs: Chimeric Molecules that Target Proteins to the Skp1-Cullin-F Box Complex for Ubiquitination and Degradation, Proc. Natl. Acad. Sci. USA 98:8554-8559.[42]
  • Crews CM, AA Alessandrini, and RL Erikson. The primary structure of MEK, a protein kinase that phosphorylates and activates the ERK gene product. Science, 258:478-480.[43]

References

  1. ^ "Staff and Editorial Board". Cell Chemical Biology. Retrieved February 28, 2018.
  2. ^ "Yale Center for Molecular Discovery". Ycmd.yale.edu. Retrieved 2016-05-05.
  3. ^ "Carfilzomib: From Discovery To Drug | August 27, 2012 Issue - Vol. 90 Issue 35 | Chemical & Engineering News". Cen.acs.org. 2012-08-27. Retrieved 2016-05-05.
  4. ^ a b c "Crews Laboratory". crewslab.yale.edu. Retrieved 2021-08-20.
  5. ^ Crews CM, Alessandrini A, Erikson RL (1992). "The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product". Science. 258 (5081): 478–80. Bibcode:1992Sci...258..478C. doi:10.1126/science.1411546. PMID 1411546.
  6. ^ Crews CM, Erikson RL (1992). "Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product". Proceedings of the National Academy of Sciences of the United States of America. 89 (17): 8205–9. Bibcode:1992PNAS...89.8205C. doi:10.1073/pnas.89.17.8205. PMC 49886. PMID 1381507.
  7. ^ a b Bond, Michael J.; Crews M., Craig (2021). "Proteolysis targeting chimeras (PROTACs) come of age: entering the third decade of targeted protein degradation". RSC Chemical Biology. 2 (3): 725–742. doi:10.1039/D1CB00011J.
  8. ^ "PROTACs: A New Type of Drug That Can Target All Disease-Causing Proteins". SciTechDaily. 2015-06-11. Retrieved 2016-05-22.
  9. ^ "Scientist wants to hijack cells' tiny garbage trucks to fight cancer". Boston Globe. 2016-05-19. Retrieved 2016-05-22.
  10. ^ "How Chemists Are Sending Bad Proteins Out With The Cellular Trash | January 18, 2016 Issue - Vol. 94 Issue 3 | Chemical & Engineering News". Cen.acs.org. 2016-01-18. Retrieved 2016-05-05.
  11. ^ Sun, Xiuyun; Gao, Hongying; Yang, Yiqing; He, Ming; Wu, Yue; Song, Yugang; Tong, Yan; Rao, Yu (2019-12-24). "PROTACs: great opportunities for academia and industry". Signal Transduction and Targeted Therapy. 4 (1): 64. doi:10.1038/s41392-019-0101-6. ISSN 2059-3635. PMC 6927964. PMID 31885879.
  12. ^ Analysis, Roots. "With Over USD 3.5 Billion in Capital Investment, and Numerous High Value Licensing Deals, the Targeted Protein Degradation Market is Anticipated to Grow at an Annualized Rate of Over 30%, Claims Roots Analysis". www.prnewswire.com. Retrieved 2020-05-12.
  13. ^ "Carfilzomib: The Latest Triumph of Targeted Therapies Development". Yale Scientific. 2012-11-10. Retrieved 2016-05-22.
  14. ^ "Dr. Craig Crews of the Crews Laboratory at Yale University describes his discovery and development of carfilzomib (Kyprolis) and what it takes to get a new drug across the "Valley of Death" - The Myeloma Crowd". 12 September 2013. Retrieved 24 April 2018.
  15. ^ Crowd, The Myeloma. "Dr. Craig Crews of the Crews Laboratory at Yale University describes his discovery and development of carfilzomib (Kyprolis) and what it takes to get a new drug across the finish line in myeloma". www.myelomacrowd.org. Retrieved 2021-08-20.
  16. ^ "Craig Crews, PhD". medicine.yale.edu. Retrieved 2021-08-20.
  17. ^ "Arvinas Presents a Platform Update, Including Initial Data from the First Two Clinical Trials of PROTAC® Targeted Protein Degraders". Arvinas. Retrieved 2020-05-12.
  18. ^ Mullard, Asher (2019-11-06). "Arvinas's PROTACs pass first safety and PK analysis". Nature Reviews Drug Discovery. 18 (12): 895. doi:10.1038/d41573-019-00188-4. PMID 31780851. S2CID 208357723.
  19. ^ "Pfizer Strengthens Cancer Standing with Protein Degrader Collaboration". BioSpace. Retrieved 2021-08-20.
  20. ^ Houlton2021-07-30T14:27:00+01:00, Sarah. "Pfizer backs protein degrader drugs with Arvinas deal". Chemistry World. Retrieved 2021-08-20.{{cite web}}: CS1 maint: numeric names: authors list (link)
  21. ^ "FDA approves Kyprolis for some patients with multiple myeloma". Fda.gov. 2012-07-20. Retrieved 2016-05-05.
  22. ^ "Onyx strikes $851M deal to buy Proteolix". FierceBiotech. Retrieved 2016-05-05.
  23. ^ Kevin McCaffrey. "Kyprolis growth prospects at center of Amgen-Onyx deal - Medical Marketing and Media". Mmm-online.com. Retrieved 2016-05-05.
  24. ^ "Awards & Honors". www.yalecancercenter.org. Retrieved 2021-08-20.
  25. ^ "2020: Professor Dr Craig M. Crews - Heinrich Wieland Prize - Homepage". www.heinrich-wieland-prize.de. Retrieved 2021-08-20.
  26. ^ "2019 Award Winners". Default. Retrieved 2021-08-20.
  27. ^ https://www.rict2018.org/speakers[permanent dead link]
  28. ^ "RSC Khorana Prize 2018 Winner". 2018-05-08. Retrieved 2018-06-01.
  29. ^ "Yale's Craig Crews is recipient of cancer research award". 2017-02-28. Retrieved 2017-03-05.
  30. ^ "Craig Crews, PhD, receives NCI's Outstanding Investigator Award". 2015-10-16. Retrieved 2016-05-22.
  31. ^ "YaleNews | Crews awarded UCB-Ehrlich Award for work on anti-cancer therapy". News.yale.edu. 2014-08-18. Retrieved 2016-05-05.
  32. ^ Bond, Michael J.; Chu, Ling; Nalawansha, Dhanusha A.; Li, Ke; Crews, Craig M. (2020-08-26). "Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs". ACS Central Science. 6 (8): 1367–1375. doi:10.1021/acscentsci.0c00411. ISSN 2374-7943. PMC 7453568. PMID 32875077.{{cite journal}}: CS1 maint: PMC format (link)
  33. ^ Cromm, Philipp M.; Samarasinghe, Kusal T. G.; Hines, John; Crews, Craig M. (2018-12-12). "Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation". Journal of the American Chemical Society. 140 (49): 17019–17026. doi:10.1021/jacs.8b08008. ISSN 0002-7863.
  34. ^ Burslem, George M.; Smith, Blake E.; Lai, Ashton C.; Jaime-Figueroa, Saul; McQuaid, Daniel C.; Bondeson, Daniel P.; Toure, Momar; Dong, Hanqing; Qian, Yimin; Wang, Jing; Crew, Andrew P. (2018-01-18). "The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study". Cell Chemical Biology. 25 (1): 67–77.e3. doi:10.1016/j.chembiol.2017.09.009. ISSN 2451-9448. PMC 5831399. PMID 29129716.
  35. ^ Salami, Jemilat; Crews, Craig M. (2017-03-17). "Waste disposal-An attractive strategy for cancer therapy". Science (New York, N.Y.). 355 (6330): 1163–1167. doi:10.1126/science.aam7340. ISSN 1095-9203. PMID 28302825.
  36. ^ Bondeson, Daniel P; Mares, Alina; Smith, Ian E D; Ko, Eunhwa; Campos, Sebastien; Miah, Afjal H; Mulholland, Katie E; Routly, Natasha; Buckley, Dennis L; Gustafson, Jeffrey L; Zinn, Nico. "Catalytic in vivo protein knockdown by small-molecule PROTACs". Nature chemical biology. 11 (8): 611–617. doi:10.1038/nchembio.1858. ISSN 1552-4450. PMC 4629852. PMID 26075522.
  37. ^ Lai, Ashton C.; Toure, Momar; Hellerschmied, Doris; Salami, Jemilat; Jaime-Figueroa, Saul; Ko, Eunhwa; Hines, John; Crews, Craig M. (2016-01-11). "Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL". Angewandte Chemie (International Ed. in English). 55 (2): 807–810. doi:10.1002/anie.201507634. ISSN 1521-3773. PMC 4733637. PMID 26593377.
  38. ^ Gustafson, Jeffrey L.; Neklesa, Taavi K.; Cox, Carly S.; Roth, Anke G.; Buckley, Dennis L.; Tae, Hyun Seop; Sundberg, Thomas B.; Stagg, D. Blake; Hines, John; McDonnell, Donald P.; Norris, John D. (2015-08-10). "Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging". Angewandte Chemie (International Ed. in English). 54 (33): 9659–9662. doi:10.1002/anie.201503720. ISSN 1521-3773. PMC 4547777. PMID 26083457.
  39. ^ Lu, Jing; Qian, Yimin; Altieri, Martha; Dong, Hanqing; Wang, Jing; Raina, Kanak; Hines, John; Winkler, James; Crew, Andrew; Coleman, Kevin; Crews, Craig (2015-06-18). "Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4". Chemistry and Biology. 22 (6): 755–763. doi:10.1016/j.chembiol.2015.05.009. ISSN 1879-1301. PMC 4475452. PMID 26051217.
  40. ^ Buckley, Dennis L.; Van Molle, Inge; Gareiss, Peter C.; Tae, Hyun Seop; Michel, Julien; Noblin, Devin J.; Jorgensen, William L.; Ciulli, Alessio; Crews, Craig M. (2012-03-14). "Targeting the von Hippel–Lindau E3 Ubiquitin Ligase Using Small Molecules To Disrupt the VHL/HIF-1α Interaction". Journal of the American Chemical Society. 134 (10): 4465–4468. doi:10.1021/ja209924v. ISSN 0002-7863. PMC 3448299. PMID 22369643.{{cite journal}}: CS1 maint: PMC format (link)
  41. ^ Schneekloth, John S.; Fonseca, Fabiana N.; Koldobskiy, Michael; Mandal, Amit; Deshaies, Raymond; Sakamoto, Kathleen; Crews, Craig M. "Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation". Journal of the American Chemical Society. 126 (12): 3748–3754. doi:10.1021/ja039025z. ISSN 0002-7863.
  42. ^ "(PDF) Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation". ResearchGate. Retrieved 2021-08-20.
  43. ^ "Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation". www.researchgate.net. Retrieved 1 August 2001.
  1. Crews lab
  2. Yale Center for Molecular Discovery
  3. Arvinas, LLC.
  4. Proteolix, Inc.
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