Adagrasib

Adagrasib
Clinical data
ATC code	None;
Legal status
Legal status	Investigational new drug;
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	2326521-71-3 ;
PubChem CID	138611145;
DrugBank	DB15568;
UNII	8EOO6HQF8Y;
KEGG	D12301;
CompTox Dashboard (EPA)	DTXSID801336759 ;
ECHA InfoCard	100.329.928
Chemical and physical data
Formula	C32H35ClFN7O2
Molar mass	604.13 g·mol−1
3D model (JSmol)	Interactive image;
	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;

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]

References

^ Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, et al. (January 2020). "The KRAS^G12C 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.
^ 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 KRAS^G12C Inhibitor for the Treatment of Cancer". Journal of Medicinal Chemistry. 63 (13): 6679–6693. doi:10.1021/acs.jmedchem.9b02052. PMID 32250617.
^ 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.
^ Christensen JG, Olson P, Briere T, Wiel C, Bergo MO (August 2020). "Targeting Kras^g12c -mutant cancer with a mutation-specific inhibitor". Journal of Internal Medicine. 288 (2): 183–191. doi:10.1111/joim.13057. PMID 32176377.
^ Dunnett-Kane V, Nicola P, Blackhall F, Lindsay C (January 2021). "Mechanisms of Resistance to KRAS^G12C Inhibitors". Cancers. 13 (1). doi:10.3390/cancers13010151. PMC 7795113. PMID 33466360.
^ 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.

[1] Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, et al. (January 2020). "The KRAS^G12C 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 KRAS^G12C 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 Kras^g12c -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 KRAS^G12C 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.

[1]

[2]

[3]

[4]

[5]

[6]

See also

References