Carbozantinib

• CAT Number: A000716
• CAS Number: 849217-68-1
• Molecular Formula: C₂₈H₂₄FN₃O₅
• Molecular Weight: 501.51
• Purity: ≥95%
• Target: c-MET
• Solubility: >25.1mg/mL in DMSO
• Storage: <label class=
• 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)
• InChIKey: ONIQOQHATWINJY-UHFFFAOYSA-N
• SMILES: COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F

Cabozantinib (cas 849217-68-1), also known as XL184 or BMS-907351, is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM in cell-free assays, respectively. Cabozantinib has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM.  Specifically, cabozantinib appears to have a strong affinity for the hepatocyte growth factor receptor (Met) and vascular endothelial growth factor receptor 2 (VEGFR2), which may result in inhibition of tumor growth and angiogenesis, and tumor regression. Cabozantinib was approved by the U.S. FDA in November 2012 for the treatment of medullary thyroid cancer.

Overview of Clinical Research

Originator: Exelixis
Developer: Bristol-Myers Squibb; Dana-Farber Cancer Institute; Duke University Medical Center; Exelixis; Ipsen; Massachusetts General Hospital; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (USA); Roche; Swedish Orphan Biovitrum; Takeda
Class: Amides; Anilides; Antineoplastics; Cyclopropanes; Fluorine compounds; Quinolines; Small molecules
Mechanism of Action: Axl receptor tyrosine kinase inhibitors; Proto oncogene protein c met inhibitors; Proto oncogene protein c ret inhibitors; Vascular endothelial growth factor receptor 3 antagonists; Vascular endothelial growth factor receptor-1 antagonists; Vascular endothelial growth factor receptor-2 antagonists
Orphan Drug Status: Yes – Thyroid cancer; Hepatocellular carcinoma
New Molecular Entity: Yes

Reference

1: Roy S, Narang BK, Rastogi SK, Rawal RK. A novel multiple tyrosine-kinase
targeted agent to explore the future perspectives of anti-angiogenic therapy for
the treatment of multiple solid tumors: cabozantinib. Anticancer Agents Med Chem.
2015;15(1):37-47. Review. PubMed PMID: 25181996.

2: Fallahi P, Ferrari SM, Di Bari F, Materazzi G, Benvenga S, Miccoli P,
Antonelli A. Cabozantinib in Thyroid Cancer. Recent Pat Anticancer Drug Discov.
2015;10(3):259-69. Review. PubMed PMID: 26152149.

3: Vaishampayan UN. Development of cabozantinib for the treatment of prostate
cancer. Core Evid. 2014 Apr 23;9:61-7. doi: 10.2147/CE.S48498. eCollection 2014.
Review. Erratum in: Core Evid. 2014;9:69. PubMed PMID: 24790591; PubMed Central
PMCID: PMC4003147.

4: Nagilla M, Brown RL, Cohen EE. Cabozantinib for the treatment of advanced
medullary thyroid cancer. Adv Ther. 2012 Nov;29(11):925-34. doi:
10.1007/s12325-012-0060-6. Epub 2012 Oct 25. Review. PubMed PMID: 23104465.

5: Durante C, Russo D, Verrienti A, Filetti S. XL184 (cabozantinib) for medullary
thyroid carcinoma. Expert Opin Investig Drugs. 2011 Mar;20(3):407-413. doi:
10.1517/13543784.2011.559163. Review. PubMed PMID: 21314233.