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Craig M. Crews

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Craig M. Crews
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 (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 the journal 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 anti-cancer drug carfilzomib (Kyprolis).[3] He is the founder of Arvinas, the first biotechnology company to bring PROTAC drugs into clinical trials.[4] In 2019, he was named an American Cancer Society Research Professor at the Yale University.[5]

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.[6] As a graduate student in the laboratory of Raymond Erikson at Harvard University, Crews purified and cloned the MAP kinase kinase MEK1,[7][8] 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.[6]

Research

Crews studies controlled proteostasis, i.e., the pharmacological modulation of protein turnover.[9] In 2001, Crews developed, in collaboration with Ray Deshaies, proteolysis targeting chimeras (PROTACs),[10][11] a new technology to induce proteolysis.[9] 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.[12] This technology has the potential to allow pharmacological targeting of proteins previously thought "undruggable" including many responsible for drug resistance in cancer.[13] Excitement around the field has resulted in much private and public investment in therapeutic approaches based on targeted protein degradation.[14] 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.[15] Subsequent medicinal chemistry efforts produced the epoxyketone containing proteasome inhibitor YU101,[16] which served as the basis for the multiple myeloma drug carfilzomib.[17][18]

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).[19] Both drugs appeared to be well tolerated and no dose-limiting toxicities or grade 2, 3 or 4 adverse events were observed.[20] Moreover, ongoing clinical trials have demonstrated evidence of efficacy, e.g., target protein level reduction and tumor shrinkage in some patients.[21][22]

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 (Kyprolis), which was approved by the FDA in 2012 for use in patients with multiple myeloma.[23] Based on successful Phase II trials of carfilzomib, Onyx Pharmaceuticals acquired Proteolix in 2009[24] and was itself acquired by Amgen in 2013.[25]

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 May 5, 2016.
  3. ^ "Carfilzomib: From Discovery To Drug | August 27, 2012 Issue – Vol. 90 Issue 35 | Chemical & Engineering News". Cen.acs.org. August 27, 2012. Retrieved May 5, 2016.
  4. ^ "Scientific Advisory Board • Arvinas".
  5. ^ "Crews Laboratory".
  6. ^ a b c "Crews Laboratory". crewslab.yale.edu. Retrieved August 20, 2021.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ "PROTACs: A New Type of Drug That Can Target All Disease-Causing Proteins". SciTechDaily. June 11, 2015. Retrieved May 22, 2016.
  11. ^ "Scientist wants to hijack cells' tiny garbage trucks to fight cancer". Boston Globe. May 19, 2016. Retrieved May 22, 2016.
  12. ^ "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. January 18, 2016. Retrieved May 5, 2016.
  13. ^ Sun X, Gao H, Yang Y, He M, Wu Y, Song Y, et al. (December 24, 2019). "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.
  14. ^ 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 May 12, 2020.
  15. ^ "Carfilzomib: The Latest Triumph of Targeted Therapies Development". Yale Scientific. November 10, 2012. Retrieved May 22, 2016.
  16. ^ "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". September 12, 2013. Retrieved April 24, 2018.
  17. ^ "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 August 20, 2021.
  18. ^ "Craig Crews, PhD". medicine.yale.edu. Retrieved August 20, 2021.
  19. ^ "Arvinas Presents a Platform Update, Including Initial Data from the First Two Clinical Trials of PROTAC® Targeted Protein Degraders". Arvinas. Retrieved May 12, 2020.
  20. ^ 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.
  21. ^ "Pfizer Strengthens Cancer Standing with Protein Degrader Collaboration". BioSpace. Retrieved August 20, 2021.
  22. ^ Houlton S (July 30, 2021). "Pfizer backs protein degrader drugs with Arvinas deal". Chemistry World. Retrieved August 20, 2021.
  23. ^ "FDA approves Kyprolis for some patients with multiple myeloma". Fda.gov. July 20, 2012. Retrieved May 5, 2016.
  24. ^ "Onyx strikes $851M deal to buy Proteolix". FierceBiotech. October 12, 2009. Retrieved May 5, 2016.
  25. ^ Kevin McCaffrey (August 26, 2013). "Kyprolis growth prospects at center of Amgen-Onyx deal – Medical Marketing and Media". Mmm-online.com. Retrieved May 5, 2016.
  26. ^ "Awards & Honors". www.yalecancercenter.org. Retrieved August 20, 2021.
  27. ^ "2020: Professor Dr Craig M. Crews – Heinrich Wieland Prize – Homepage". www.heinrich-wieland-prize.de. Retrieved August 20, 2021.
  28. ^ "Crews Laboratory".
  29. ^ "2019 Award Winners". Default. Retrieved August 20, 2021.
  30. ^ https://www.rict2018.org/speakers[permanent dead link‍]
  31. ^ "RSC Khorana Prize 2018 Winner". May 8, 2018. Retrieved June 1, 2018.
  32. ^ "Yale's Craig Crews is recipient of cancer research award". February 28, 2017. Retrieved March 5, 2017.
  33. ^ "Craig Crews, PhD, receives NCI's Outstanding Investigator Award". October 16, 2015. Retrieved May 22, 2016.
  34. ^ "YaleNews | Crews awarded UCB-Ehrlich Award for work on anti-cancer therapy". News.yale.edu. August 18, 2014. Retrieved May 5, 2016.
  35. ^ "Scientific Advisory Board • Arvinas".
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