Craig M. Crews
Craig M. Crews | |
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File:Craig Crews.jpg | |
Born | June 1, 1964 | (age 60)
Alma mater | University of Virginia Harvard University |
Known for | Proteolysis Targeting Chimeras (PROTACs) Controlled Proteostasis Carfilzomib |
Awards | Swedish 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 | |
Fields | Chemical Biology |
Institutions | Yale University |
Doctoral advisors | Raymond 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
- 2021: Honorary Doctoral Degree, Technische Universität Dortmund, Germany (doctor rerum naturalium honoris causa)[4]
- 2020: Swedish Pharmaceutical Society Scheele Award[24]
- 2020: Boehringer Ingelheim Foundation Heinrich Wieland Prize[25]
- 2019: Pharmacia-ASPET Award for Experimental Therapeutics[26]
- 2018: Pierre Fabre Award [27]
- 2018: Royal Society of Chemistry Khorana Prize [28]
- 2017: AACR Award for Outstanding Achievement in Chemistry in Cancer Research[29]
- 2015: Inaugural Recipient of the National Cancer Institute Outstanding Investigator Award (R35)[30]
- 2014: UCB-Ehrlich Award for Excellence in Medicinal Chemistry[31]
Publications
- Bond MJ, Chu L, Nalawansha DA, Li K, Crews CM (August 2020). "Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs". ACS Central Science. 6 (8): 1367–1375. doi:10.1021/acscentsci.0c00411. PMC 7453568. PMID 32875077.</ref>
- Cromm PM, Samarasinghe KT, Hines J, Crews CM (December 2018). "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. PMID 30444612.
- Burslem GM, Smith BE, Lai AC, Jaime-Figueroa S, McQuaid DC, Bondeson DP, et al. (January 2018). "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. PMC 5831399. PMID 29129716.
- Salami J, Crews CM (March 2017). "Waste disposal-An attractive strategy for cancer therapy". Science. 355 (6330): 1163–1167. Bibcode:2017Sci...355.1163S. doi:10.1126/science.aam7340. PMID 28302825.
- Bondeson DP, Mares A, Smith IE, Ko E, Campos S, Miah AH, et al. (August 2015). "Catalytic in vivo protein knockdown by small-molecule PROTACs". Nature Chemical Biology. 11 (8): 611–7. doi:10.1038/nchembio.1858. PMC 4629852. PMID 26075522.
- Lai AC, Toure M, Hellerschmied D, Salami J, Jaime-Figueroa S, Ko E, et al. (January 2016). "Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL". Angewandte Chemie. 55 (2): 807–10. doi:10.1002/anie.201507634. PMC 4733637. PMID 26593377.
- Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae HS, et al. (August 2015). "Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging". Angewandte Chemie. 54 (33): 9659–62. doi:10.1002/anie.201503720. PMC 4547777. PMID 26083457.
- Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, et al. (June 2015). "Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4". Chemistry & Biology. 22 (6): 755–63. doi:10.1016/j.chembiol.2015.05.009. PMC 4475452. PMID 26051217.
- Buckley DL, Van Molle I, Gareiss PC, Tae HS, Michel J, Noblin DJ, et al. (March 2012). "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): 4465–8. doi:10.1021/ja209924v. PMC 3448299. PMID 22369643.
- Schneekloth JS, Fonseca FN, Koldobskiy M, Mandal A, Deshaies R, Sakamoto K, Crews CM (March 2004). "Chemical genetic control of protein levels: selective in vivo targeted degradation". Journal of the American Chemical Society. 126 (12): 3748–54. doi:10.1021/ja039025z. PMID 15038727.
- Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ (July 2001). "Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation". Proceedings of the National Academy of Sciences of the United States of America. 98 (15): 8554–9. Bibcode:2001PNAS...98.8554S. doi:10.1073/pnas.141230798. PMC 37474. PMID 11438690.
- Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ (July 2001). "Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation". Proceedings of the National Academy of Sciences of the United States of America. 98 (15): 8554–9. Bibcode:2001PNAS...98.8554S. doi:10.1073/pnas.141230798. PMC 37474. PMID 11438690.
References
- ^ "Staff and Editorial Board". Cell Chemical Biology. Retrieved February 28, 2018.
- ^ "Yale Center for Molecular Discovery". Ycmd.yale.edu. Retrieved 2016-05-05.
- ^ "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.
- ^ a b c "Crews Laboratory". crewslab.yale.edu. Retrieved 2021-08-20.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ "PROTACs: A New Type of Drug That Can Target All Disease-Causing Proteins". SciTechDaily. 2015-06-11. Retrieved 2016-05-22.
- ^ "Scientist wants to hijack cells' tiny garbage trucks to fight cancer". Boston Globe. 2016-05-19. Retrieved 2016-05-22.
- ^ "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.
- ^ 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.
- ^ 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.
- ^ "Carfilzomib: The Latest Triumph of Targeted Therapies Development". Yale Scientific. 2012-11-10. Retrieved 2016-05-22.
- ^ "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.
- ^ "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.
- ^ "Craig Crews, PhD". medicine.yale.edu. Retrieved 2021-08-20.
- ^ "Arvinas Presents a Platform Update, Including Initial Data from the First Two Clinical Trials of PROTAC® Targeted Protein Degraders". Arvinas. Retrieved 2020-05-12.
- ^ 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.
- ^ "Pfizer Strengthens Cancer Standing with Protein Degrader Collaboration". BioSpace. Retrieved 2021-08-20.
- ^ Houlton S (30 July 2021). "Pfizer backs protein degrader drugs with Arvinas deal". Chemistry World. Retrieved 2021-08-20.
- ^ "FDA approves Kyprolis for some patients with multiple myeloma". Fda.gov. 2012-07-20. Retrieved 2016-05-05.
- ^ "Onyx strikes $851M deal to buy Proteolix". FierceBiotech. Retrieved 2016-05-05.
- ^ 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.
- ^ "Awards & Honors". www.yalecancercenter.org. Retrieved 2021-08-20.
- ^ "2020: Professor Dr Craig M. Crews - Heinrich Wieland Prize - Homepage". www.heinrich-wieland-prize.de. Retrieved 2021-08-20.
- ^ "2019 Award Winners". Default. Retrieved 2021-08-20.
- ^ https://www.ldorganisation.com/v2/produits.php?cle_menus=1238916573
- ^ "RSC Khorana Prize 2018 Winner". 2018-05-08. Retrieved 2018-06-01.
- ^ "Yale's Craig Crews is recipient of cancer research award". 2017-02-28. Retrieved 2017-03-05.
- ^ "Craig Crews, PhD, receives NCI's Outstanding Investigator Award". 2015-10-16. Retrieved 2016-05-22.
- ^ "YaleNews | Crews awarded UCB-Ehrlich Award for work on anti-cancer therapy". News.yale.edu. 2014-08-18. Retrieved 2016-05-05.