Cabozantinib (free base)
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MedKoo CAT#: 200595

CAS#: 849217-68-1 (free base)

Description: Cabozantinib, also known as XL-184 or BMS-907351, is an orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several tyrosine receptor kinases. 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.


Chemical Structure

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Cabozantinib (free base)
CAS# 849217-68-1 (free base)

Theoretical Analysis

MedKoo Cat#: 200595
Name: Cabozantinib (free base)
CAS#: 849217-68-1 (free base)
Chemical Formula: C28H24FN3O5
Exact Mass: 501.17
Molecular Weight: 501.51
Elemental Analysis: C, 67.06; H, 4.82; F, 3.79; N, 8.38; O, 15.95

Price and Availability

Size Price Availability Quantity
200.0mg USD 150.0 Ready to ship
500.0mg USD 250.0 Ready to ship
1.0g USD 450.0 Ready to ship
2.0g USD 750.0 Ready to ship
5.0g USD 1250.0 Ready to ship
10.0g USD 1950.0 Ready to ship
20.0g USD 3450.0 Ready to ship
50.0g USD 4950.0 2 Weeks
100.0g USD 8250.0 2 Weeks
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Related CAS #: 1140909-48-3 (malate)   849217-68-1 (free base)  

Synonym: XL-184; XL184; XL 184; BMS 907351; BMS-907351; BMS907351; Cabozantinib, Cabozantinib free base; trade name Cometriq

IUPAC/Chemical Name: N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1- dicarboxamide

InChi Key: ONIQOQHATWINJY-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=C(C1(C(NC2=CC=C(F)C=C2)=O)CC1)NC3=CC=C(OC4=CC=NC5=CC(OC)=C(OC)C=C45)C=C3

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Cabozantinib is a multiple receptor tyrosine kinases (RTKs) inhibitor that inhibits VEGFR2, c-Met, Kit, Axl and Flt3 with IC50s of 0.035, 1.3, 4.6, 7 and 11.3 nM, respectively.
In vitro activity: As shown in Figure 1B, CBZ (Cabozantinib), at a non-toxic concentration (5 μM), could significantly decrease the IC50 value of TPT in NCI-H460/TPT10 cells. The cross-resistance to other ABCG2 substrates in NCI-H460/TPT10 cells, including mitoxantrone and SN-38, could also be reversed by CBZ with comparable potency to the ABCG2 inhibitor Ko143 (Table 1). On the other hand, the IC50 value of cisplatin, which is not a substrate of ABCG2, was not affected by co-administration of 5 μM CBZ (Figure 1C). Furthermore, CBZ could restore TPT accumulation in ABCG2 overexpressing NCI-H460/TPT10 cells (Figures 1D,E). These observations indicated that the CBZ can alleviate TPT resistance most likely by increasing intracellular TPT level, which could be a result from the ABCG2 inhibitory effect of CBZ. A slight reduction of TPT IC50 and elevation of TPT accumulation in parental NCI-H460 cells treated with CBZ were observed (Figures 1B,D,E), possibly due to the endogenous ABCG2 expression in NCI-H460 cells. Reference: Front Cell Dev Biol. 2021; 9: 640957. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019832/
In vivo activity: To further confirm the role of CBZ (Cabozantinib) in the alleviation of CNV (choroidal neovascularization), CBZ oral gavage at the dose of 200 or 300 mg/kg/day was performed on the same day of laser injury and analysis was performed at 14 d (Figure 5(a)). FFA showed decreased CNV leakage in the CBZ groups (Figure 5(b), a, b, and c). Leakage score analysis also showed that the grade percentage of score 0 and score 1 increased, while the grade percentage of score 2b was decreased in the CBZ groups (Figure 5(c)). IB4 and phalloidin double staining indicated that the CNV lesion area was decreased in the CBZ groups (Figure 5(b) (d-3, e-3, f-3) and 5(d)). Additionally, CBZ oral gavage downregulated the HGF, p-MET, and p-VEGFR2 protein levels in CNV in the 14 d groups (Figures 5(e) and 5(f)). Furthermore, CBZ showed no effect on vascular leakage and formation in the normal mice (Figure 5(b)). The results suggest that CBZ oral gavage mitigates CNV leakage and the CNV lesion area via restraining the phosphorylation of MET and VEGFR2. Reference: J Ophthalmol. 2020; 2020: 5905269. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322600/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 46.29 92.3
DMSO:PBS (pH 7.2) (1:2) 0.3 0.6
DMF 3.0 5.98
Ethanol 2.0 3.99

Preparing Stock Solutions

The following data is based on the product molecular weight 501.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Lei ZN, Teng QX, Gupta P, Zhang W, Narayanan S, Yang DH, Wurpel JND, Fan YF, Chen ZS. Cabozantinib Reverses Topotecan Resistance in Human Non-Small Cell Lung Cancer NCI-H460/TPT10 Cell Line and Tumor Xenograft Model. Front Cell Dev Biol. 2021 Mar 22;9:640957. doi: 10.3389/fcell.2021.640957. PMID: 33829017; PMCID: PMC8019832. 2. Pan T, Martinez M, Hubka KM, Song JH, Lin SC, Yu G, Lee YC, Gallick GE, Tu SM, Harrington DA, Farach-Carson MC, Lin SH, Satcher RL. Cabozantinib Reverses Renal Cell Carcinoma-mediated Osteoblast Inhibition in Three-dimensional Coculture In Vitro and Reduces Bone Osteolysis In Vivo. Mol Cancer Ther. 2020 Jun;19(6):1266-1278. doi: 10.1158/1535-7163.MCT-19-0174. Epub 2020 Mar 27. PMID: 32220969; PMCID: PMC7272308. 3. Labrecque MP, Brown LG, Coleman IM, Nguyen HM, Lin DW, Corey E, Nelson PS, Morrissey C. Cabozantinib can block growth of neuroendocrine prostate cancer patient-derived xenografts by disrupting tumor vasculature. PLoS One. 2021 Jan 20;16(1):e0245602. doi: 10.1371/journal.pone.0245602. PMID: 33471819; PMCID: PMC7817027. 4. Zhang X, Zhu M, Xie L, Sun X, Xu J, Guo Y, Liu D, Shi Y, Xu X, Song E. Cabozantinib, a Multityrosine Kinase Inhibitor of MET and VEGF Receptors Which Suppresses Mouse Laser-Induced Choroidal Neovascularization. J Ophthalmol. 2020 Jun 19;2020:5905269. doi: 10.1155/2020/5905269. PMID: 32655941; PMCID: PMC7322600.
In vitro protocol: 1. Lei ZN, Teng QX, Gupta P, Zhang W, Narayanan S, Yang DH, Wurpel JND, Fan YF, Chen ZS. Cabozantinib Reverses Topotecan Resistance in Human Non-Small Cell Lung Cancer NCI-H460/TPT10 Cell Line and Tumor Xenograft Model. Front Cell Dev Biol. 2021 Mar 22;9:640957. doi: 10.3389/fcell.2021.640957. PMID: 33829017; PMCID: PMC8019832. 2. Pan T, Martinez M, Hubka KM, Song JH, Lin SC, Yu G, Lee YC, Gallick GE, Tu SM, Harrington DA, Farach-Carson MC, Lin SH, Satcher RL. Cabozantinib Reverses Renal Cell Carcinoma-mediated Osteoblast Inhibition in Three-dimensional Coculture In Vitro and Reduces Bone Osteolysis In Vivo. Mol Cancer Ther. 2020 Jun;19(6):1266-1278. doi: 10.1158/1535-7163.MCT-19-0174. Epub 2020 Mar 27. PMID: 32220969; PMCID: PMC7272308.
In vivo protocol: 1. Labrecque MP, Brown LG, Coleman IM, Nguyen HM, Lin DW, Corey E, Nelson PS, Morrissey C. Cabozantinib can block growth of neuroendocrine prostate cancer patient-derived xenografts by disrupting tumor vasculature. PLoS One. 2021 Jan 20;16(1):e0245602. doi: 10.1371/journal.pone.0245602. PMID: 33471819; PMCID: PMC7817027. 2. Zhang X, Zhu M, Xie L, Sun X, Xu J, Guo Y, Liu D, Shi Y, Xu X, Song E. Cabozantinib, a Multityrosine Kinase Inhibitor of MET and VEGF Receptors Which Suppresses Mouse Laser-Induced Choroidal Neovascularization. J Ophthalmol. 2020 Jun 19;2020:5905269. doi: 10.1155/2020/5905269. PMID: 32655941; PMCID: PMC7322600.

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1: Weitzman SP, Cabanillas ME. The treatment landscape in thyroid cancer: a focus on cabozantinib. Cancer Manag Res. 2015 Aug 19;7:265-78. doi: 10.2147/CMAR.S68373. eCollection 2015. Review. PubMed PMID: 26316818; PubMed Central PMCID: PMC4547654.

2: Zhang B, Zhang X, Zhou T, Liu J. Clinical observation of liver cancer patients treated with axitinib and cabozantinib after failed sorafenib treatment: a case report and literature review. Cancer Biol Ther. 2015;16(2):215-8. doi: 10.4161/15384047.2014.962318. Review. PubMed PMID: 25668362; PubMed Central PMCID: PMC4622678.

3: Fay AP, Albiges L, Bellmunt J. Current role of cabozantinib in metastatic castration-resistant prostate cancer. Expert Rev Anticancer Ther. 2015 Feb;15(2):151-6. doi: 10.1586/14737140.2015.1003047. Epub 2015 Jan 14. Review. PubMed PMID: 25586337.

4: 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.

5: Hoy SM. Cabozantinib: a review of its use in patients with medullary thyroid cancer. Drugs. 2014 Aug;74(12):1435-44. doi: 10.1007/s40265-014-0265-x. Review. PubMed PMID: 25056653.

6: Nix NM, Braun K. Cabozantinib for the treatment of metastatic medullary thyroid carcinoma. J Adv Pract Oncol. 2014 Jan;5(1):47-50. Review. PubMed PMID: 25032033; PubMed Central PMCID: PMC4093460.

7: Colombo JR, Wein RO. Cabozantinib for progressive metastatic medullary thyroid cancer: a review. Ther Clin Risk Manag. 2014 May 28;10:395-404. doi: 10.2147/TCRM.S46041. eCollection 2014. Review. PubMed PMID: 24920914; PubMed Central PMCID: PMC4043815.

8: 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.

9: Grüllich C. Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. Recent Results Cancer Res. 2014;201:207-14. doi: 10.1007/978-3-642-54490-3_12. Review. PubMed PMID: 24756794.

10: Pinto A. Cabozantinib: a novel agent with a dual mechanism of action for castration-resistant prostate carcinoma. Cancer Chemother Pharmacol. 2014 Feb;73(2):219-22. doi: 10.1007/s00280-013-2343-2. Epub 2013 Nov 8. Review. PubMed PMID: 24202668.

11: Karras S, Pontikides N, Krassas GE. Pharmacokinetic evaluation of cabozantinib for the treatment of thyroid cancer. Expert Opin Drug Metab Toxicol. 2013 Apr;9(4):507-15. doi: 10.1517/17425255.2013.780028. Review. PubMed PMID: 23488614.

12: 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.

13: Bowles DW, Kessler ER, Jimeno A. Multi-targeted tyrosine kinase inhibitors in clinical development: focus on XL-184 (cabozantinib). Drugs Today (Barc). 2011 Nov;47(11):857-68. doi: 10.1358/dot.2011.47.11.1688487. Review. PubMed PMID: 22146228.

14: 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.



Additional Information

Related CAS#
CAS#849217-68-1 (Cabozantinib free base);
CAS#1140909-48-3 (Cabozantinib malate salt).

Cabozantinib (Marketed under the tradename Cometriq, formerly known as XL184) 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 developed by Exelixis Inc. Cabozantinib was granted orphan-drug status by the U.S. Food and Drug Administration (FDA) in January 2011. Cabozantinib was approved by the U.S. FDA in November 2012 for the treatment of medullary thyroid cancer[2] and it is currently undergoing clinical trials for the treatment of prostate, ovarian, brain, melanoma, breast, non-small cell lung, hepatocellular and kidney cancers. (source: http://en.wikipedia.org/wiki/Cabozantinib).