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| doctoral_students =
| doctoral_students =
| known_for = [[Proteolysis Targeting Chimera|Proteolysis Targeting Chimeras (PROTACs)]]<br />Controlled [[Proteostasis]]<br />[[Carfilzomib]]
| known_for = [[Proteolysis Targeting Chimera|Proteolysis Targeting Chimeras (PROTACs)]]<br />Controlled [[Proteostasis]]<br />[[Carfilzomib]]
| prizes = [[:de:Friedrich Wilhelm Bessel-Forschungspreis|Friedrich Wilhelm Bessel Research Award (Alexander von Humboldt Foundation) (2005)]]<br />[http://www.efmc.info/content.php?langue=english&amp;cle_menus=1176114008 UCB-Ehrlich Award for Excellence in Medicinal Chemistry (2014)]<br />[http://www.cancer.gov/research/nci-role/spotlight/oia National Cancer Institute Outstanding Investigator Award (2015)]<br />[http://www.aacr.org/Research/Awards/Pages/aacr-award-for-outstanding-achievement-in-chemistry-in-cancer-research___8470D6.aspx#.WLx5tfnyvD4 AACR Award for Outstanding Achievement in Chemistry in Cancer Research (2017)]<br />[https://www.rict2018.org/speakers Pierre Fabre Award (2018)]<br />[http://www.rsc.org/ScienceAndTechnology/Awards/KhoranaPrize/2018-Winner.asp RSC Khorana Prize (2018)]<br />[https://www.yalecancercenter.org/research/excellence/awards/ Swedish Pharmaceutical Society Scheele Award (2020)]<br />[https://www.heinrich-wieland-prize.de/laureates/since-2020/articles/id-2020-professor-dr-craig-m-crews.html Boehringer Ingelheim Foundation Heinrich Wieland Prize (2020)]<br />[https://www.aspet.org/aspet/meetings-awards/aspet-awards/aspet-scientific-achievement-awards/aspet-award-winners/2019-award-winners Pharmacia-ASPET Award for Experimental Therapeutics (2019)]<br />[https://news.yale.edu/yale-s-craig-crews-recipient-cancer-research-award AACR Award for Outstanding Achievement in Chemistry in Cancer Research (2017)]
| prizes = [https://www.yalecancercenter.org/research/excellence/awards/ Swedish Pharmaceutical Society Scheele Award (2020)]<br />[https://www.heinrich-wieland-prize.de/laureates/since-2020/articles/id-2020-professor-dr-craig-m-crews.html Boehringer Ingelheim Foundation Heinrich Wieland Prize (2020)]<br />[https://www.aspet.org/aspet/meetings-awards/aspet-awards/aspet-scientific-achievement-awards/aspet-award-winners/2019-award-winners Pharmacia-ASPET Award for Experimental Therapeutics (2019)]<br />[https://www.ldorganisation.com/v2/produits.php?cle_menus=1238916573 Pierre Fabre Award (2018)]<br />
[http://www.rsc.org/ScienceAndTechnology/Awards/KhoranaPrize/2018-Winner.asp RSC Khorana Prize (2018)]
| religion =
| religion =
| footnotes =
| footnotes =
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*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>
*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>
*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.ldorganisation.com/v2/produits.php?cle_menus=1238916573</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|access-date=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|access-date=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 |access-date=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 |access-date=2017-03-05}}</ref>

Revision as of 09:56, 9 September 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
AwardsSwedish Pharmaceutical Society Scheele Award (2020)
Boehringer Ingelheim Foundation Heinrich Wieland Prize (2020)
Pharmacia-ASPET Award for Experimental Therapeutics (2019)
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

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 (October 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 (September 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 MJ, Crews CM (March 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. PMC 8190915. PMID 34212149.
  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 X, Gao H, Yang Y, He M, Wu Y, Song Y, et al. (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. PMC 6927964. PMID 31885879.
  12. ^ Roots Analysis. "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". Cision. 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. ^ "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". The Myeloma Crowd. 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 A (November 2019). "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. ^ Houlton S (30 July 2021). "Pfizer backs protein degrader drugs with Arvinas deal". Chemistry World. Retrieved 2021-08-20.
  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 (26 August 2013). "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.ldorganisation.com/v2/produits.php?cle_menus=1238916573
  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.
  1. Crews lab
  2. Yale Center for Molecular Discovery
  3. Arvinas, LLC.
  4. Proteolix, Inc.
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