AMG 510

AMG 510 is an experimental cancer drug. It targets a specific mutation, G12C, in the protein KRAS which is responsible for various forms of cancer.[1][2]

AMG 510
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC30H30F2N6O3
Molar mass560.606 g·mol−1
3D model (JSmol)

Clinical development

AMG 510 is being developed by Amgen and, as of 2019, it is in Phase 1/2 clinical trials.[3][4]

Because the G12C KRAS mutation is relatively common in some cancer types, 14% of non-small-cell lung cancer adenocarcinoma patients and 5% of colorectal cancer patients,[5] and AMG 510 is the first drug candidate to target this mutation, there have been high expectations for the drug.[5][6][7] The Food and Drug Administration has granted a fast track designation to AMG 510 for the treatment of metastatic non-small-cell lung carcinoma with the G12C KRAS mutation.[8]

Chemistry and pharmacology

AMG 510 can exist in either of two atropisomeric forms and one is more active than the other.[5] It selectively forms an irreversible covalent bond to the sulfur atom in the cysteine residue that is present in the mutated form of KRAS, but not in the normal form.[5]

References
  1. "KRAS mutant-targeting AMG 510". NCI Drug Dictionary. National Cancer Institute. 2011-02-02. Retrieved November 16, 2019.
  2. Canon, Jude; Rex, Karen; Saiki, Anne Y.; Mohr, Christopher; Cooke, Keegan; Bagal, Dhanashri; Gaida, Kevin; Holt, Tyler; Knutson, Charles G.; Koppada, Neelima; Lanman, Brian A.; Werner, Jonathan; Rapaport, Aaron S.; San Miguel, Tisha; Ortiz, Roberto; Osgood, Tao; Sun, Ji-Rong; Zhu, Xiaochun; McCarter, John D.; Volak, Laurie P.; Houk, Brett E.; Fakih, Marwan G.; o'Neil, Bert H.; Price, Timothy J.; Falchook, Gerald S.; Desai, Jayesh; Kuo, James; Govindan, Ramaswamy; Hong, David S.; et al. (2019). "The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity". Nature. 575 (7781): 217–223. doi:10.1038/s41586-019-1694-1. PMID 31666701.
  3. "A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation". clinicaltrials.gov. Retrieved November 16, 2019.
  4. "The Discovery Of Amgen's Novel Investigational KRAS(G12C) Inhibitor AMG 510 Published In Nature" (Press release). Amgen. October 30, 2019. Retrieved November 16, 2019.
  5. Bethany Halford (April 3, 2019). "Amgen unveils its KRas inhibitor in human clinical trials: AMG 510 shuts down a mutant version of the cancer target via covalent interaction". Chemical & Engineering News. 97 (4). Retrieved November 16, 2019.
  6. Amirah Al Idrus (September 9, 2019). "Amgen's KRAS drug continues to deliver but faces 'curse' of high expectations". fiercebiotech.com. Retrieved November 16, 2019.
  7. Kaiser J (2019-10-30). "Two new drugs finally hit 'undruggable' cancer target, providing hope for treatments". Science Magazine. AAAS. Retrieved November 16, 2019.
  8. Lisa Astor (September 9, 2019). "FDA Grants AMG 510 Fast Track Designation for KRAS G12C+ NSCLC". targetedonc.com. Retrieved November 16, 2019.
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