Craig M. Crews

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 a former Editor of Cell Chemical Biology[1] and the Executive Director of the Yale Center for Molecular Discovery.[2] His research interests focus on Chemical Biology, particularly on controlled proteostasis. Crews has been 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]

Craig M. Crews
BornJune 1, 1964 (1964-06) (age 56)
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)

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. As a graduate student in the laboratory of Raymond Erikson at Harvard University, Crews purified and cloned the MAP kinase kinase MEK1,[4][5] 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.

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 Chimeras),[6][7] a new technology to induce proteolysis. 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.[8] This technology has the potential to allow pharmacological targeting of proteins previously thought "undruggable" including many responsible for drug resistance in cancer[9]. 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[10]. 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.[11] Subsequent medicinal chemistry efforts produced the epoxyketone containing proteasome inhibitor YU101,[12] which served as the basis for the multiple myeloma drug Carfilzomib (Kyprolis®).

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 2015, Arvinas partnered with Merck[13] and Genentech[14] to develop PROTAC-based drugs. In 2018, Arvinas signed a $830M plus deal with Pfizer.[15] 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[16]. 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)[17]. Both drugs appeared to be well tolerated and no dose-limiting toxicities or grade 2, 3 or 4 adverse events were observed[18]. Further updates are expected at the ASCO Annual Meeting in 2020.

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.[19] Based on successful Phase II trials of carfilzomib, Onyx Pharmaceuticals acquired Proteolix in 2009 [20] and was itself acquired by Amgen in 2013 for $10.4 billion.[21]

Awards and recognition

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. 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. doi:10.1126/science.1411546. PMID 1411546.
  5. 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. doi:10.1073/pnas.89.17.8205. PMC 49886. PMID 1381507.
  6. "PROTACs: A New Type of Drug That Can Target All Disease-Causing Proteins". SciTechDaily. 2015-06-11. Retrieved 2016-05-22.
  7. "Scientist wants to hijack cells' tiny garbage trucks to fight cancer". Boston Globe. 2016-05-19. Retrieved 2016-05-22.
  8. "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.
  9. 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): 1–33. doi:10.1038/s41392-019-0101-6. ISSN 2059-3635.
  10. 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.
  11. "Carfilzomib: The Latest Triumph of Targeted Therapies Development". Yale Scientific. 2012-11-10. Retrieved 2016-05-22.
  12. "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.
  13. "Merck wagers $434M on Arvinas and its protein-disposal system". FierceBiotech. Retrieved 2016-05-05.
  14. "Genentech embraces Arvinas with $300M tie-up on protein degradation". FierceBiotech. Retrieved 2016-05-05.
  15. "Arvinas in $830M-plus Pfizer biobucks deal". FierceBiotech. Retrieved 2018-01-04.
  16. "Bayer and Arvinas Unveil Targeted Protein Degradation Joint Venture, Oerth Bio". Arvinas. Retrieved 2020-02-14.
  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: 895–895. doi:10.1038/d41573-019-00188-4.
  19. "FDA approves Kyprolis for some patients with multiple myeloma". Fda.gov. 2012-07-20. Retrieved 2016-05-05.
  20. "Onyx strikes $851M deal to buy Proteolix". FierceBiotech. Retrieved 2016-05-05.
  21. Kevin McCaffrey. "Kyprolis growth prospects at center of Amgen-Onyx deal - Medical Marketing and Media". Mmm-online.com. Retrieved 2016-05-05.
  22. https://www.rict2018.org/speakers%5B%5D
  23. "RSC Khorana Prize 2018 Winner". 2018-05-08. Retrieved 2018-06-01.
  24. "Yale's Craig Crews is recipient of cancer research award". 2017-02-28. Retrieved 2017-03-05.
  25. "Craig Crews, PhD, receives NCI's Outstanding Investigator Award". 2015-10-16. Retrieved 2016-05-22.
  26. "Craig M. Crews, PhD receives the Yale Cancer Center Translational Research Prize". 2015-11-25. Retrieved 2016-05-22.
  27. "YaleNews | Crews awarded UCB-Ehrlich Award for work on anti-cancer therapy". News.yale.edu. 2014-08-18. Retrieved 2016-05-05.
  28. "CURE Entrepreneur of the Year Award – CURE :: Connecticut's Bioscience Innovation Network". Cureconnect.org. 2014-06-20. Archived from the original on 2016-04-28. Retrieved 2016-05-05.
  29. Dodson, Helen (2013-12-02). "YaleNews | Yale faculty elected to world's largest scientific society". News.yale.edu. Retrieved 2016-05-05.
  30. "2011 Senior Scholar Award In Aging". Ellisonfoundation.org. Archived from the original on 2016-05-13. Retrieved 2016-05-05.
  31. "Using HIV against itself". Retrieved 24 April 2018.
  32. Zagorski, Nick. "The Humboldt Foundation". Asbmb.org. Retrieved 2016-05-05.
  33. http://www.mikemilken.com/pdfs/pcf_annual_2003.pdf
  34. "Awards and Accolades - July 2009 | Burroughs Wellcome Fund". Bwfund.org. Retrieved 2016-05-05.
  1. Crews lab
  2. Yale Center for Molecular Discovery
  3. Arvinas, LLC.
  4. Proteolix, Inc.
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