WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H200595
CAS#: 849217-68-1 (free base)
Description: Cabozantinib, also known as XL-184 and BMS-907351, is the s-malate salt form of cabozantinib, an orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression. Cabozantinib was approved by the U.S. FDA in November 2012 for the treatment of medullary thyroid cancer.
Hodoodo Cat#: H200595
Name: Cabozantinib free base
CAS#: 849217-68-1 (free base)
Chemical Formula: C28H24FN3O5
Exact Mass: 501.17
Molecular Weight: 501.510
Elemental Analysis: C, 67.06; H, 4.82; F, 3.79; N, 8.38; O, 15.95
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
More Info: 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).
| 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/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 46.3 | 92.30 | |
| DMSO:PBS (pH 7.2) (1:2) | 0.3 | 0.60 | |
| DMF | 3.0 | 5.98 | |
| Ethanol | 2.0 | 3.99 |
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.
| 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. |
1: Graham J, Vogel A, Cheng AL, Bjarnason GA, Neal JW. Cabozantinib after prior checkpoint inhibitor therapy in patients with solid tumors: A systematic literature review. Cancer Treat Rev. 2022 Nov;110:102453. doi: 10.1016/j.ctrv.2022.102453. Epub 2022 Aug 10. PMID: 36037792.
2: Castellano D, Apolo AB, Porta C, Capdevila J, Viteri S, Rodriguez-Antona C, Martin L, Maroto P. Cabozantinib combination therapy for the treatment of solid tumors: a systematic review. Ther Adv Med Oncol. 2022 Jul 30;14:17588359221108691. doi: 10.1177/17588359221108691. PMID: 35923927; PMCID: PMC9340935.
3: Maroto P, Porta C, Capdevila J, Apolo AB, Viteri S, Rodriguez-Antona C, Martin L, Castellano D. Cabozantinib for the treatment of solid tumors: a systematic review. Ther Adv Med Oncol. 2022 Jul 13;14:17588359221107112. doi: 10.1177/17588359221107112. PMID: 35847482; PMCID: PMC9284205.
4: Iaxx R, Lefort F, Domblides C, Ravaud A, Bernhard JC, Gross-Goupil M. An Evaluation of Cabozantinib for the Treatment of Renal Cell Carcinoma: Focus on Patient Selection and Perspectives. Ther Clin Risk Manag. 2022 Jun 2;18:619-632. doi: 10.2147/TCRM.S251673. PMID: 35677148; PMCID: PMC9169675.
5: Azhie A, Grant RC, Herman M, Wang L, Knox JJ, Bhat M. Phase II clinical trial of cabozantinib for the treatment of recurrent hepatocellular carcinoma after liver transplantation. Future Oncol. 2022 Jun;18(18):2173-2191. doi: 10.2217/fon-2021-1635. Epub 2022 Mar 15. PMID: 35287469.
6: Markham A. Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. Target Oncol. 2022 Mar;17(2):193-201. doi: 10.1007/s11523-022-00866-1. Epub 2022 Feb 17. PMID: 35175500.
7: McGregor B, Mortazavi A, Cordes L, Salabao C, Vandlik S, Apolo AB. Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. Cancer Treat Rev. 2022 Feb;103:102333. doi: 10.1016/j.ctrv.2021.102333. Epub 2021 Dec 24. PMID: 35033866; PMCID: PMC9590624.
8: Meza L, Malhotra J, Favorito C, Pal SK. Cabozantinib plus immunotherapy combinations in metastatic renal cell and urothelial carcinoma. Future Oncol. 2022 Jan;18(1):21-33. doi: 10.2217/fon-2021-0570. Epub 2021 Nov 12. PMID: 34766841.
9: Deng S, Solinas A, Calvisi DF. Cabozantinib for HCC Treatment, From Clinical Back to Experimental Models. Front Oncol. 2021 Oct 13;11:756672. doi: 10.3389/fonc.2021.756672. PMID: 34722310; PMCID: PMC8548824.
10: Santoni M, Iacovelli R, Colonna V, Klinz S, Mauri G, Nuti M. Antitumor effects of the multi-target tyrosine kinase inhibitor cabozantinib: a comprehensive review of the preclinical evidence. Expert Rev Anticancer Ther. 2021 Sep;21(9):1029-1054. doi: 10.1080/14737140.2021.1919090. Epub 2021 Aug 27. PMID: 34445927.
11: Marchetti A, Rosellini M, Rizzo A, Mollica V, Battelli N, Massari F, Santoni M. An up-to-date evaluation of cabozantinib for the treatment of renal cell carcinoma. Expert Opin Pharmacother. 2021 Dec;22(17):2323-2336. doi: 10.1080/14656566.2021.1959548. Epub 2021 Aug 18. PMID: 34405738.
12: El-Khoueiry AB, Hanna DL, Llovet J, Kelley RK. Cabozantinib: An evolving therapy for hepatocellular carcinoma. Cancer Treat Rev. 2021 Jul;98:102221. doi: 10.1016/j.ctrv.2021.102221. Epub 2021 May 12. PMID: 34029957.
13: D'Alessio A, Prete MG, Cammarota A, Personeni N, Rimassa L. The Role of Cabozantinib as a Therapeutic Option for Hepatocellular Carcinoma: Current Landscape and Future Challenges. J Hepatocell Carcinoma. 2021 Mar 29;8:177-191. doi: 10.2147/JHC.S268310. PMID: 33824862; PMCID: PMC8018438.
14: Trojan J. Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. Drugs. 2020 Aug;80(12):1203-1210. doi: 10.1007/s40265-020-01361-5. PMID: 32671719; PMCID: PMC7395054.
15: Roy AM, Briggler A, Tippit D, Dawson K, Verma R. Neoadjuvant Cabozantinib in Renal-Cell Carcinoma: A Brief Review. Clin Genitourin Cancer. 2020 Dec;18(6):e688-e691. doi: 10.1016/j.clgc.2020.04.003. Epub 2020 Apr 21. PMID: 32660880.
16: Castellano D, Pablo Maroto J, Benzaghou F, Taguieva N, Nguyen L, Clary DO, Jonasch E. Exposure-response modeling of cabozantinib in patients with renal cell carcinoma: Implications for patient care. Cancer Treat Rev. 2020 Sep;89:102062. doi: 10.1016/j.ctrv.2020.102062. Epub 2020 Jun 24. PMID: 32659623.
17: Debaillon Vesque A, Decraecker M, Blanc JF. Profile of Cabozantinib for the Treatment of Hepatocellular Carcinoma: Patient Selection and Special Considerations. J Hepatocell Carcinoma. 2020 Jun 9;7:91-99. doi: 10.2147/JHC.S195570. PMID: 32607316; PMCID: PMC7293396.
18: Rathi N, Maughan BL, Agarwal N, Swami U. Mini-Review: Cabozantinib in the Treatment of Advanced Renal Cell Carcinoma and Hepatocellular Carcinoma. Cancer Manag Res. 2020 May 20;12:3741-3749. doi: 10.2147/CMAR.S202973. PMID: 32547210; PMCID: PMC7246323.
19: Schöffski P, Blay JY, Ray-Coquard I. Cabozantinib as an emerging treatment for sarcoma. Curr Opin Oncol. 2020 Jul;32(4):321-331. doi: 10.1097/CCO.0000000000000644. PMID: 32541320.
20: D'Angelo A, Sobhani N, Bagby S, Casadei-Gardini A, Roviello G. Cabozantinib as a second-line treatment option in hepatocellular carcinoma. Expert Rev Clin Pharmacol. 2020 Jun;13(6):623-629. doi: 10.1080/17512433.2020.1767591. Epub 2020 May 22. PMID: 32394749.
