Casdatifan

Casdatifan
Clinical data
Other names	AB-521
Identifiers
	IUPAC name (5R,6S,8R)-3,5,6-Trifluoro-8-[(1S,2R)-2-fluoro-1-hydroxy-7-methylsulfonyl-2,3-dihydro-1H-inden-4-yl]-5,6,7,8-tetrahydronaphthalene-1-carbonitrile;
CAS Number	2709069-30-5;
PubChem CID	156859185;
IUPHAR/BPS	13981;
DrugBank	DB21701;
UNII	DP73UWL6LE;
KEGG	D13257;
ChEBI	CHEBI:760136;
ChEMBL	ChEMBL6068220;
Chemical and physical data
Formula	C21H17F4NO3S
Molar mass	439.42 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CS(=O)(=O)C1=C2[C@@H]([C@@H](CC2=C(C=C1)[C@H]3C[C@@H]([C@@H](C4=CC(=CC(=C34)C#N)F)F)F)F)O;
	InChI InChI=1S/C21H17F4NO3S/c1-30(28,29)17-3-2-11(13-7-16(24)21(27)19(13)17)12-6-15(23)20(25)14-5-10(22)4-9(8-26)18(12)14/h2-5,12,15-16,20-21,27H,6-7H2,1H3/t12-,15+,16-,20-,21-/m1/s1; Key:KHBHHNNBNHHGPE-QCCZFBHPSA-N;

Casdatifan is an investigational new drug that is being evaluated by Arcus Biosciences and AstraZeneca for the treatment of renal cell carcinoma.^[1] It is an inhibitor of endothelial PAS domain-containing protein 1 (HIF‑2α).^[2]^[3]^[4]

Pharmacology

Casdatifan is allosteric HIF‑2α inhibitor with low-nanomolar potency in cell-based reporter assays.^[3]

Casdatifan in combination with cabozantinib (a tyrosine-kinase inhibitor) is currently in phase 3 clinical trials for the treatment of advanced clear cell renal cell carcinoma.^[4]^[5]

↑ "Casdatifan - Arcus Biosciences". AdisInsight. Springer Nature Switzerland AG.
↑ Mata G, Mailyan AK, Drew SL, Beatty JW, Fournier J, Rosen BR, et al. (June 2026). "Discovery of Casdatifan, Part I: Design and Characterization of Tetrahydroquinoline Inhibitors of Hypoxia-Inducible Factor-2α". Journal of Medicinal Chemistry. 69 (12): 14921–14951. doi:10.1021/acs.jmedchem.5c03647. PMID 42053090.
1 2 Mailyan AK, Mata G, Beatty JW, Drew SL, Fournier J, Yu K, et al. (June 2026). "Discovery of Casdatifan, Part II: A Potent and Orally Bioavailable Inhibitor of Hypoxia Inducible Factor-2α". Journal of Medicinal Chemistry. 69 (12): 14952–14988. doi:10.1021/acs.jmedchem.5c03724. PMID 42246926.
1 2 Dogra R, Vaishampayan U (2025). "Hypoxia Inducible Factor-2α (HIF-2α) Pathway Inhibitors". Journal of Kidney Cancer and VHL. 12 (3): 1–15. doi:10.15586/jkc.v12i3.413. PMC 12228116. PMID 40620865.
↑ Clinical trial number NCT07011719 for "Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma" at ClinicalTrials.gov