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Cabozantinib

Anti-cancer drugs Mechanism of action Pharmacokinetics Side effects Medicine interactions
Cabozantinib
Cabozantinib structure
CAS No.
849217-68-1
Chemical Name:
Cabozantinib
Synonyms
CS-6;XL184;XL-186;BMS907351;Cabozantinib;Carbozantinib;Carbozanitinb;XL184 free base;XL184; BMS-907351;Capmatinib??XL184
CBNumber:
CB72525898
Molecular Formula:
C28H24FN3O5
Formula Weight:
502
MOL File:
849217-68-1.mol

Cabozantinib Properties

Boiling point:
758.1±60.0 °C(Predicted)
Density 
1.396
form 
White powder.
pka
13.86±0.70(Predicted)
FDA UNII
1C39JW444G

Cabozantinib price More Price(4)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 18464 XL184 ≥98% 849217-68-1 1mg $35 2020-06-24 Buy
Cayman Chemical 18464 XL184 ≥98% 849217-68-1 5mg $79 2020-06-24 Buy
Cayman Chemical 18464 XL184 ≥98% 849217-68-1 10mg $123 2020-06-24 Buy
Cayman Chemical 18464 XL184 ≥98% 849217-68-1 50mg $438 2020-06-24 Buy

Cabozantinib Chemical Properties,Uses,Production

Anti-cancer drugs

Cabozantinib is a kind of a novel type of molecular targeted drugs developed by the United States Exelixis biopharmaceutical company. On November 29, 2012, the US Food and Drug Administration (FDA) approved the use of cabozantinib for the treatment of unresectable malignant local advanced or metastatic medullary thyroid carcinoma.
In addition, Sorafenib, Vandernib and Levotinib have been approved by the Food and Drug Administration (FDA) for the treatment of advanced thyroid cancer.

Mechanism of action

In vitro biochemical and/or cytological analysis have shown that cabozantinib can inhibit the tyrosine kinase activity of RET, human hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 1 (VEGFR-1, VEGFR-2, VEGFR-3, stem cell factor receptor (KIT), receptor kinase receptor (TRKB), FMS-like tyrosine kinase-3, FLT-3), AXL and human tyrosine kinase with immunoglobulinlike and EGF-like domains 2, TIE-2. All the above kinase receptors play an important role in the growth of normal cells and tumor cells. The abnormal expression of these receptors is critical in the development and progression of many kinds of tumors, including the inhibition of tumor cell apoptosis, participating into the tumor angiogenesis and invasion and other pathological processes. Cabozantinib exerts its antitumor effect by inhibiting the above kinase activity, killing tumor cells, reducing metastasis and inhibiting tumor angiogenesis.

Pharmacokinetics

The pharmacokinetic analysis showed that the half-life of this drug was about 55 h with the volume of distribution (V/F) being about 349L, and the clearance rate of CLL being about 4.4 L • h-1. Upon oral administration of this drug, the time for reaching plasma concentration peak time (tmax) is 2~5h. Compared with a single dose of oral administration of 140 mg • d ^ (-1) for 19 days, the exposure amount in vivo was increased to 4-5 times (based on the area under the drug-time curve) and can reach steady-state in 15th day. The drug has a high binding rate with plasma protein (≥ 99.7%).
For healthy people subjecting to a single oral dose of 140 mg of this drug, a high-fat diet compared with the administration upon empty stomach, the maximal concentration (Cmax) and AUC are increased by 41% and 57%, respectively.
In vitro studies have shown that cabozantinib is a CYP3A4 substrate. The CYP3A4 inhibitor will reduce the formation of its metabolite N-oxide (> 80%) while CYP2A9 inhibitor has a relatively small effect on the drug metabolism (<20%). CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP2E1 have no effect on the drug metabolism.
After a single dose of radiolabeled cabozantinib was administered to healthy subjects, 27% of the radioactivity appeared in the urine and 54% in the stool.

Side effects

In clinical trials, common adverse effects caused by cabozantinib include diarrhea, stomatitis, palmar-plantarrythrodysesthesia syndrome (PPES), and loss of weight, loss of appetite, nausea, fatigue, oral pain, taste disorders, high blood pressure, abdominal pain and constipation.
The most common laboratory abnormalities (> 25%) were increased aspartate aminotransferase, alanine aminotransferase, lymphopenia, increased alkaline phosphatase level, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia and hyperbilirubinemia.
For patients receiving cabozantinib, 57% of patients have gotten increased level of thyroid stimulating hormone after initial dose, compared with patients receiving placebo, increased by 19%.
Information regarding to the anticancer drug, mechanism of action, pharmacokinetics, side effects, and drug interactions of cabozantinib were compiled and edited by Yan Shi from Chemicalbook. (2015-10-23)

Medicine interactions

To healthy subjects, administration of strong CYP3A4 inhibitor, ketoconazole (400 mg • d-1, 27 days) can increase the single dose exposure amount (AUC0-inf) of the drug by 38%. Upon administration of this drug, it should be avoided of taking potent CYP3A4 drugs inhibitors such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole).
To healthy subjects, administration of strong CYP3A4 inducing drugs, rifampicin (600mg • d-1, a total of 31 d) can reduce the single dose exposure amount (AUC0-inf) of the drug by 77%. It should be avoided of simultaneously administration CYP3A4 induced drugs (such as dexamethasone, Phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital and hypericum perforatum preparation).
In the human liver microsomal (HLM) enzyme system, cabozantinib is the noncompetitive inhibitor of CYP2C8, CYP2C9 mixed inhibitor and the weak competitive inhibitor of CYP2C19 and CYP3A4.
In the cultured human hepatocytes, carbotinib is a kind of CYP1A1 mRNA induction drug, but has no effect on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or CYP3A4 mRNA or its isozyme system.
In patients with solid tumors, the steady-state plasma concentration of carbotinib (≥100 mg • d-1 for a total of at least 21 days) showed no significant influence on plasma exposure amount (Cmax and AUC) of single doses of rosiglitazone (CYP2C8 substrate).
Carbotinib is a P-glycoprotein transport inhibitory drug, but is not its substrate. Therefore, carbotinib may increase the plasma concentration of P-glycoprotein substrate.

Description

Cabozantinib was approved inNovember 2012 for the treatment of patients with progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). Cabozantinib was granted orphan drug status by the FDA to facilitate development of newtreatment options for patients with MTC. It is a member of a class of tyrosine kinase inhibitors (TKIs) with nanomolar pan-inhibitory activity against VEGFR2, MET, and RET among others. Inhibition of the VEGF pathway has been shown preclinically to initially slow tumor growth, but rapid revascularization is followed by aggressive tumor growth. The MET pathway has been implicated in the development of VEGF resistance, so dual VEGF/MET activity is viewed as desirable. In addition, mutations in RET play a particular role in MTC, with 25% of the tumors inheriting a germlinemutation in the proto-oncogene, so multiple tyrosine kinase inhibition may be viewed as particularly beneficial for the treatment of MTC.

Originator

Exelixis (United States)

Uses

Cabozantinib (XL184, 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, respectively

Definition

ChEBI: A dicarboxylic acid diamide that is N-phenyl-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide in which the hydrogen at position 4 on the phenyl ring is substituted by a (6,7-dimethoxyquinolin-4-yl)oxy group. A multi-t rosine kinase inhibitor, used (as its malate salt) for the treatment of progressive, metastatic, medullary thyroid cancer.

brand name

Cometriq

Cabozantinib Preparation Products And Raw materials

Raw materials

Preparation Products


Cabozantinib Suppliers

Global( 248)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Nanjing Gold Pharmaceutical Technology Co. Ltd.
025-84209270 15906146951
025-84209270 wgp@nanjing-pharmaceutical.com CHINA 115 55
Jurong Coupling Biotechnology Co., Ltd.
13656108824
coupling278191416@hotmail.com CHINA 184 58
Capot Chemical Co.,Ltd.
+86-571-85586718
+86-571-85864795 sales@capotchem.com China 19929 60
Henan DaKen Chemical CO.,LTD.
+86-371-55531817
info@dakenchem.com CHINA 21821 58
Beijing Cooperate Pharmaceutical Co.,Ltd.
+86-10-60279497 +86(0)15646567669
+86-10-60279497 sales01@cooperate-pharm.com CHINA 1817 55
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 22626 55
Nanjing ChemLin Chemical Industry Co., Ltd.
025-83697070
product@chemlin.com.cn CHINA 3014 60
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 24723 60
Shandonghaohong biotechnology Co.,ltd.
0635-6175299 13961496334
0635-6175299 sale@inyelchem.com CHINA 44 55
Anqing Chico Pharmaceutical Co., Ltd.
15380796838
chloewu@chicopharm.cn CHINA 341 58

Related articles


View Lastest Price from Cabozantinib manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2019-08-28 Cabozantinib (XL184)
849217-68-1
US $0.00-0.00 / KG 1ASSAYS 99.0% 50kg/month Beijing Yibai Biotechnology Co., Ltd
2019-08-27 Carbozanitinb
849217-68-1
US $0.00-0.00 / KG 1g 99.0% 500kg/month Beijing Yibai Biotechnology Co., Ltd
2018-07-26 Cabozantinib
849217-68-1
US $10.00 / KG 1KG 98% 200KG career henan chemical co

849217-68-1(Cabozantinib)Related Search:


  • XL184; CABOZANTINIB; BMS907351; BMS-907351; BMS 907351
  • Carbozantinib
  • Cabozantinib(XL184Malate)
  • Cabozantinib (XL184, BMS-907351)
  • N-(4-(6,7-diMethoxyquinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxaMide(CAS:849217-68-1)
  • XL-186
  • N-[4-[(6,7-Dimethoxy-4-quinolinyl)oxy]phenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide Cabozantinib (XL184, BMS-907351)
  • 1,1-cyclopropanedicarboxamide, n'-[4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl]-n-(4-fluorophenyl)-
  • Cabozantinib, >=98%
  • Carbozanitinb
  • CS-6
  • N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Cabozantinib
  • Cabozantinib(BMS907351)
  • 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
  • Cabozantinib Base
  • N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
  • Cabozantinib
  • N-[4-[(6,7-Dimethoxy-4-quinolinyl)oxy]phenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide
  • XL184
  • Cabozantinib(XL184)
  • XL-184 free base (Cabozantinib)
  • BMS907351
  • XL184; BMS-907351
  • N-(4-((6,7-DiMethoxyquino...
  • Cyclopropane-1,1-dicarboxylic acid [4-(6,7-diMethoxy-quinoline-4-yloxy)-phenyl]-aMide (4-fluoro-phenyl)-aMide
  • XL184 Cabozantinib
  • XL184 free base
  • Cabozantinib(free base)
  • CABOZANTINIB(FREE BASE)
  • Capmatinib??XL184
  • XL-184 (Cabozantinib,BMS907351)
  • 849217-68-1
  • C28H24FN3O5
  • Inhibitors
  • API
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