Tesevatinib

Tesevatinib (KD019, XL647) is an experimental drug proposed for use in kidney cancer and polycystic kidney disease. The drug was first developed by Exelixis, Inc.^[1] and was later acquired by Kadmon Corporation. Tesevatinib binds to and inhibits several tyrosine receptor kinases that play major roles in tumor cell proliferation and tumor vascularization, including epidermal growth factor receptor (EGFR; ERBB1), epidermal growth factor receptor 2 (HER2; ERBB2), vascular endothelial growth factor receptor (VEGFR), and ephrin B4 (EphB4).^[2]

Tesevatinib

Clinical data
Routes of administration	Oral administration (tablets)
Pharmacokinetic data
Elimination half-life	50–70 hours
Identifiers
IUPAC name N-(3,4-dichloro-2-fluorophenyl)-6-methoxy-7-{[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methoxy}quinazolin-4-amine
CAS Number	781613-23-8 Y
PubChem CID	10458325
DrugBank	DB11973 Y
ChemSpider	32699556 Y
UNII	F6XM2TN5A1
KEGG	D11772 Y
Chemical and physical data
Formula	C24H25Cl2FN4O2
Molar mass	491.39 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN1C[C@H]2C[C@H](C[C@H]2C1)COc3cc4c(cc3OC)c(ncn4)Nc5ccc(c(c5F)Cl)Cl
InChI InChI=1S/C24H25Cl2FN4O2/c1-31-9-14-5-13(6-15(14)10-31)11-33-21-8-19-16(7-20(21)32-2)24(29-12-28-19)30-18-4-3-17(25)22(26)23(18)27/h3-4,7-8,12-15H,5-6,9-11H2,1-2H3,(H,28,29,30)/t13-,14-,15+ Y Key:HVXKQKFEHMGHSL-QKDCVEJESA-N Y

The drug activity was initially studied in non-small cell lung cancer.^[3] In a 2007 pre-clinical study with xenograft tumors of an erlotinib-resistant cell line tesevatinib substantially inhibited the growth of these tumors.^[4] In polycystic kidney disease, a histological study of the drug effects and toxicity in rats and mice was published in July 2017.^[5]

As of March 2019 the drug was in Phase II clinical trials for the treatment of polycystic kidney disease in adults and children.^[6]