Cabozantinib

Cabozantinib

Clinical data
Trade names	Cabometyx, Cometriq
License data	US FDA: Cabozantinib
Pregnancy category	US: D (Evidence of risk)
Routes of administration	Oral
ATC code	L01XE26 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Protein binding	≥99.7%
Metabolism	Hepatic (CYP3A4-mediated)
Biological half-life	55 hours
Excretion	Faeces (54%), urine (27%)
Identifiers
IUPAC name N-(4-((6,7-Dimethoxyquinolin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Synonyms	XL184, BMS907351
CAS Number	849217-68-1
ChemSpider	25948202
UNII	1C39JW444G
KEGG	D10062
ChEBI	CHEBI:72317 Y
ChEMBL	CHEMBL2105717
ECHA InfoCard	100.221.147
Chemical and physical data
Formula	C28H24FN3O5
Molar mass	501.51 g mol
3D model (Jmol)	Interactive image
SMILES O=C(C1(CC1)C(NC2=CC=C(F)C=C2)=O)NC(C=C3)=CC=C3OC4=C(C=C(OC)C(OC)=C5)C5=NC=C4
InChI InChI=1S/C28H24FN3O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34) Key:ONIQOQHATWINJY-UHFFFAOYSA-N

Cabozantinib, marketed under the trade name Cabometyx among others, is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, and has been shown to reduce tumor growth, metastasis, and angiogenesis. It was discovered and developed by Exelixis Inc.

Cabozantinib was granted orphan drug status by the U.S. Food and Drug Administration (FDA) in January 2011. Cabozantinib is approved by the U.S. FDA for medullary thyroid cancer. and advanced renal cell carcinoma in people who have received prior anti-angiogenic therapy. It is currently undergoing clinical trials for the treatment of prostate, bladder, ovarian, brain, melanoma, breast, non-small cell lung, pancreatic, and hepatocellular cancers.

Cabozantinib will be distributed in Europe by the French pharmaceutical company Ipsen after a collaboration was reached with Exelixis in March 2016.

In October 2011, cabozantinib met its primary endpoint in a phase 3 clinical trial (EXAM) conducted by Exelixis investigating its effect on progression-free survival in medullary thyroid cancer. A new drug application was submitted in the first half of 2012, and on November 29, 2012 cabozantinib in its capsule formulation was granted marketing approval by the U.S. FDA under the name Cometriq for treating patients with medullary thyroid cancer.

Approval for its tablet formulation was granted for treating people with kidney cancer on April 25th, 2016.

Grapefruit and grapefruit juice should be avoided as they may increase the concentration of the drug in the blood. It is not yet known if cabozantinib is safe and effective in children.

It is undergoing clinical trials for the treatment of prostate, ovarian, brain, melanoma, breast, non-small cell lung, hepatocellular and kidney cancers.