Cabozantinib

Bezeichnung:Cabozantinib

CAS-Nr849217-68-1

Englisch Name:Cabozantinib

CBNumberCB72525898

SummenformelC28H24FN3O5

Molgewicht501.51

MOL-Datei849217-68-1.mol

Cabozantinib physikalisch-chemischer Eigenschaften

Schmelzpunkt	212-215°C
Siedepunkt	758.1±60.0 °C(Predicted)
Dichte	1.396
storage temp.	-20°C
Löslichkeit	Soluble in DMSO
Aggregatzustand	White powder.
pka	13.86±0.70(Predicted)
Farbe	White
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
InChIKey	ONIQOQHATWINJY-UHFFFAOYSA-N
SMILES	C1(C(NC2=CC=C(OC3C4C(N=CC=3)=CC(OC)=C(OC)C=4)C=C2)=O)(C(NC2=CC=C(F)C=C2)=O)CC1

Gefahreninformationscode (GHS)

Cabozantinib Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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)
Verwenden
XL184 can be used in biological study. Computational network biological approach based on pathway cross-talk inhibition identified new synergistic drug combinations using raloxifene and cabozantinib for treatment of human breast cancer in xenograft mouse model. Potent c-MET inhibitor.
Verwenden
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.
Trademarks
Cometriq
Allgemeine Beschreibung
Class:receptor tyrosine kinase; Treatment: MTC; RCC; HCC; Other name: XL-184, BMS-907351; Elimination half-life = 110 h; Protein binding > 99.7%
Clinical Use
Cabozantinib (PF-06463922; brand name Cabometyx; Exelixis, Alameda, CA) is an oral multikinase inhibitor with CNS penetration. It is FDA approved for use in medullary thyroid cancer and as a second-line agent in advanced renal cell carcinoma. In vitro studies found it to exhibit excellent activity against both the wild-type ROS1 fusion and the G2032R and G2026M mutations at concentrations less than 30?nmol/L—a dose much lower than what is clinically achievable [71, 91]. It has been found to inhibit CD74-ROS1-transformed Ba/F3 cells with more potency than entrectinib, brigatinib, lorlatinib [92], or foretinib [71].
target
RET/VEGFR
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antibacterials: concentration possibly increased by clarithromycin and erythromycin; concentration reduced by rifampicin - avoid.
Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone - avoid.
Antipsychotics: avoid with clozapine - increased risk of agranulocytosis.
Stoffwechsel
Cabozantinib is metabolised mostly by CYP3A4 and, to a minor extent, by CYP2C9. Both enzymes produce an N-oxide metabolite. Cabozantinib is eliminated mainly by the faeces (54%) and also by the urine (27%).
Lager
Store at +4°C
Einzelnachweise
1) Yakes?et al.?(2011),?Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth; Mol. Cancer Ther.,?10?2298 2) You?et al.?(2011),?VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer; Cancer Res.,?71?4758 3) Kurzrock?et al.?(2011),?Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor in patients with medullary thyroid cancer; J. Clin. Oncol.,?29?2660

Cabozantinib Upstream-Materialien And Downstream Produkte

Cabozantinib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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