Apatinib (also known as YN968D1) is an orally bioavailable, small molecule inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR2, also known as KDR). Apatinib specifically inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. Apatinib also mildly inhibits c-Kit and c-SRC tyrosine kinases. Apatinib (YN968D1) significantly enhanced the cytotoxicity of ABCB1 or ABCG2 substrate drugs in KBv200, MCF-7/adr, and HEK293/ABCB1 cells overexpressing ABCB1 and in S1-M1-80, MCF-7/FLV1000, and HEK293/ABCG2-R2 cells overexpressing ABCG2 (wild-type). Apatinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin in the multidrug resistance (MDR) cells. Furthermore, apatinib (YN968D1) significantly increased the ATPase activity of both ABCB1 and ABCG2.
|Cell lines||HUVEC cells|
|Preparation method||Cell proliferation assays.
The HUVEC were seeded into 96-well plates. After 24 h of incubation, cells were exposed to the test agents (vehicle as control) together with 20 ng⁄ mL VEGF or 20% FBS for another 72 h. After fixation with 10% trichloroacetic acid, the cells were stained with 0.4% sulforhodamine B for 30 min at 37C and then washed with 1% acetic acid. Tris was added to dissolve the complex, and the optical density was measured at 520 nm.
|Concentrations||0.1 and 1μM|
|Incubation time||72 h|
|Animal models||Ls174t, HCT 116, SGC-7901, HT-29, A549, NCI-H460 cells tumour xenograft in BALB/cA nude mice|
|Formulation||0.5% (w ⁄ v) carboxymethyl cellulose and 5% (w ⁄ v) glucose solution|
|Dosages||50, 100, 200 mg/kg once daily for 14, 18 or 21days|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 20 mg/mL|
Apatinib (YN968D1) enhances the efficacy of conventional chemotherapeutical drugs in side population cells and ABCB1-overexpressing leukemia cells.
Tong XZ, et al. Biochem Pharmacol. 2012 Mar 1;83(5):586-97. PMID: 22212563.
YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo.
Tian S, et al. Cancer Sci. 2011 Jul;102(7):1374-80. PMID: 21443688.
Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters.
Mi YJ, et al. Cancer Res. 2010 Oct 15;70(20):7981-91. PMID: 20876799.
|Related VEGFR/PDGFR Products|
Avitinib maleate is a pyrrolopyrimidine-based irreversible epidermal growth factor receptor (EGFR) inhibitor with an IC50 of 7.68 nM.
SUN11602 is a novel aniline compound with basic fibroblast growth factor-like activity.
Anlotinib Dihydrochloride is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFRα/β, c-Kit, and Ret.
Sunitinib is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit.
Avapritinib (BLU-285) is a small molecule kinase inhibitor that potently inhibits PDGFRα D842V mutant activity in vitro (IC50 = 0.5 nM) and PDGFRα D842V autophosphorylation in the cellular setting (IC50 = 30 nM); also a potent inhibitor of the analogous KIT mutation, D816V in KIT Exon 17 (IC50 = 0.5 nM).
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