Adagrasib

Adagrasib (INN, codenamed MRTX-849), is an experimental cancer drug being developed by Mirati Therapeutics. It acts as a covalently binding inhibitor for a mutant form of the protein KRAS called G12C, which is commonly present in various forms of cancer and acts as a growth factor. It has shown promising results in pre-clinical testing and is currently in clinical trials.[1][2][3][4][5][6]

Adagrasib
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
IUPAC name
  • {(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2S)-1methylpyrrolidin-2-yl]methoxy}-5,6,7,8tetrahydropyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop2-enoyl)piperazin-2-yl}acetonitrile
CAS Number
PubChem CID
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC32H35ClFN7O2
Molar mass604.13 g·mol−1
3D model (JSmol)
SMILES
  • CN1CCC[C@H]1COC2=NC3=C(CCN(C3)C4=CC=CC5=C4C(=CC=C5)Cl)C(=N2)N6CCN([C@H](C6)CC#N)C(=O)C(=C)F
InChI
  • InChI=1S/C32H35ClFN7O2/c1-21(34)31(42)41-17-16-40(18-23(41)11-13-35)30-25-12-15-39(28-10-4-7-22-6-3-9-26(33)29(22)28)19-27(25)36-32(37-30)43-20-24-8-5-14-38(24)2/h3-4,6-7,9-10,23-24H,1,5,8,11-12,14-20H2,2H3/t23-,24-/m0/s1
  • Key:PEMUGDMSUDYLHU-ZEQRLZLVSA-N

See also

References
  1. Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, et al. (January 2020). "The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients". Cancer Discovery. 10 (1): 54–71. doi:10.1158/2159-8290.CD-19-1167. PMC 6954325. PMID 31658955.
  2. Fell JB, Fischer JP, Baer BR, Blake JF, Bouhana K, Briere DM, et al. (July 2020). "Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer". Journal of Medicinal Chemistry. 63 (13): 6679–6693. doi:10.1021/acs.jmedchem.9b02052. PMID 32250617.
  3. Thein KZ, Biter AB, Hong DS (January 2021). "Therapeutics Targeting Mutant KRAS". Annual Review of Medicine. 72: 349–364. doi:10.1146/annurev-med-080819-033145. PMID 33138715.
  4. Christensen JG, Olson P, Briere T, Wiel C, Bergo MO (August 2020). "Targeting Krasg12c -mutant cancer with a mutation-specific inhibitor". Journal of Internal Medicine. 288 (2): 183–191. doi:10.1111/joim.13057. PMID 32176377.
  5. Dunnett-Kane V, Nicola P, Blackhall F, Lindsay C (January 2021). "Mechanisms of Resistance to KRASG12C Inhibitors". Cancers. 13 (1). doi:10.3390/cancers13010151. PMC 7795113. PMID 33466360.
  6. Jänne, Pasi A.; Riely, Gregory J.; Gadgeel, Shirish M.; Heist, Rebecca S.; Ou, Sai-Hong I.; Pacheco, Jose M.; Johnson, Melissa L.; Sabari, Joshua K.; Leventakos, Konstantinos; Yau, Edwin; Bazhenova, Lyudmila; Negrao, Marcelo V.; Pennell, Nathan A.; Zhang, Jun; Anderes, Kenna (2022-07-14). "Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation". New England Journal of Medicine. 387 (2): 120–131. doi:10.1056/NEJMoa2204619. ISSN 0028-4793. PMID 35658005.
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