PF-06372222

PF-06372222
Clinical data
ATC code	None;
Identifiers
	IUPAC name 3-[[4-[(R)-(3,3-dimethylcyclobutyl)-[[6-[4-(trifluoromethyl)imidazol-1-yl]-3-pyridinyl]amino]methyl]benzoyl]amino]propanoic acid;
CAS Number	1407592-99-7;
PubChem CID	68178630;
IUPHAR/BPS	9575;
ChemSpider	34450722;
ChEMBL	ChEMBL3648185;
PDB ligand	97Y (PDBe, RCSB PDB);
Chemical and physical data
Formula	C26H28F3N5O3
Molar mass	515.537 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1(CC(C1)[C@H](C2=CC=C(C=C2)C(=O)NCCC(=O)O)NC3=CN=C(C=C3)N4C=C(N=C4)C(F)(F)F)C;
	InChI InChI=1S/C26H28F3N5O3/c1-25(2)11-18(12-25)23(16-3-5-17(6-4-16)24(37)30-10-9-22(35)36)33-19-7-8-21(31-13-19)34-14-20(32-15-34)26(27,28)29/h3-8,13-15,18,23,33H,9-12H2,1-2H3,(H,30,37)(H,35,36)/t23-/m0/s1; Key:MYZIDYJMNWEJMC-QHCPKHFHSA-N;

PF-06372222 is a drug which acts as a potent and selective allosteric antagonist of both the glucagon receptor and the glucagon-like peptide-1 receptor (GLP-1). It was originally developed as a potential treatment for diabetes but was unsuccessful, however it has subsequently been used as a pharmacological tool compound for the study of the GLP-1 receptor and led to the discovery of non-peptide GLP-1 agonists such as orforglipron.^[1]^[2]^[3]^[4]

References

↑ Guzman-Perez A, Pfefferkorn JA, Lee EC, Stevens BD, Aspnes GE, Bian J, et al. (15 May 2013). "The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus". Bioorganic & Medicinal Chemistry Letters. 23 (10): 3051–3058. doi:10.1016/j.bmcl.2013.03.014. PMID 23562063.
↑ Song G, Yang D, Wang Y, de Graaf C, Zhou Q, Jiang S, et al. (8 June 2017). "Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators". Nature. 546 (7657): 312–315. Bibcode:2017Natur.546..312S. doi:10.1038/nature22378. PMID 28514449.
↑ Wu F, Yang L, Hang K, Laursen M, Wu L, Han GW, et al. (9 March 2020). "Full-length human GLP-1 receptor structure without orthosteric ligands". Nature Communications. 11 (1) 1272. Bibcode:2020NatCo..11.1272W. doi:10.1038/s41467-020-14934-5. PMC 7062719. PMID 32152292.{{cite journal}}: CS1 maint: unflagged free DOI (link)
↑ Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, et al. (24 November 2020). "Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist". Proceedings of the National Academy of Sciences of the United States of America. 117 (47): 29959–29967. Bibcode:2020PNAS..11729959K. doi:10.1073/pnas.2014879117. PMC 7703558. PMID 33177239.

[1] Guzman-Perez A, Pfefferkorn JA, Lee EC, Stevens BD, Aspnes GE, Bian J, et al. (15 May 2013). "The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus". Bioorganic & Medicinal Chemistry Letters. 23 (10): 3051–3058. doi:10.1016/j.bmcl.2013.03.014. PMID 23562063.

[2] Song G, Yang D, Wang Y, de Graaf C, Zhou Q, Jiang S, et al. (8 June 2017). "Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators". Nature. 546 (7657): 312–315. Bibcode:2017Natur.546..312S. doi:10.1038/nature22378. PMID 28514449.

[3] Wu F, Yang L, Hang K, Laursen M, Wu L, Han GW, et al. (9 March 2020). "Full-length human GLP-1 receptor structure without orthosteric ligands". Nature Communications. 11 (1) 1272. Bibcode:2020NatCo..11.1272W. doi:10.1038/s41467-020-14934-5. PMC 7062719. PMID 32152292.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[4] Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, et al. (24 November 2020). "Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist". Proceedings of the National Academy of Sciences of the United States of America. 117 (47): 29959–29967. Bibcode:2020PNAS..11729959K. doi:10.1073/pnas.2014879117. PMC 7703558. PMID 33177239.

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See also

References