Tesevatinib

SKU: orb1296161

Description

Tesevatinib (XL-647) is an orally bioavailable, multi-targeted tyrosine kinase inhibitor. It potently inhibits EGFR, ErbB2, KDR, Flt4, and EphB4 with low nanomolar IC50 values. This compound has been utilized in preclinical research for studying cancers and angiogenesis in both cellular and animal models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 781613-23-8
• MW: 491.39
• Purity: 99.99% (May vary between batches)
• Formula: C₂₄H₂₅Cl₂FN₄O₂
• SMILES: COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@H]1C[C@H]2CN(C)C[C@H]2C1
• Target: Src,VEGFR,Ephrin Receptor,EGFR,FLT
• Solubility: DMSO:45 mg/mL (91.58 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.07 mM)

Bioactivity

• Target IC50:
  FLT4:8.7 nM|ErbB2:16 nM|KDR:1.5 nM|EGFR:0.3 nM
• In Vivo:
  METHODS: To study the in vivo effects of Tesevatinib (XL-647) on T790M mutant EGFR, H1975 human tumor xenografts were established in female severe combined immunodeficient mice and administered Tesevatinib (XL-647) orally once daily (doses: 10, 30 and 100 mg/kg, 14 days) RESULTS Tesevatinib (XL-647) significantly inhibited tumor growth in a dose-dependent manner, with tumor growth inhibition rates of 33%, 66% and 92% respectively. METHODS: Tesevatinib (XL-647) (7.5, 15 mg/kg, ip, daily) was treated in the well-characterized bpk mouse model of ARPKD, and efficacy and toxicity were evaluated in neonatal mice during postnatal development. RESULTS In vivo pharmacological inhibition of multiple kinase cascades by tesevatinib (XL-647) reduced phosphorylation of key mediators of cystogenesis: EGFR, ErbB2, c-Src, and KDR; decreased kinase activity resulted in significant reductions in renal and biliary disease in both the bpk and PCK models of ARPKD. Disease amelioration by tesevatinib (XL-647) was not associated with any overt toxicity.
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• In Vitro:
  Tesevatinib (XL-647) potently inhibits the EGF/ErbB2, VEGF, and ephrin RTK families with IC50 values ​​of 0.3, 16, 1.5, 8.7, and 1.4 nM for EGFR, ErbB2, KDR, and EphB4.
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• Cell Research:
  Growth inhibition of H1975 and A431 cells by increasing concentrations of Tesevatinib is determined by seeding 5000 cells per well in 96-well plates. The following day, cells are washed once with low-serum RPMI 1640 (0.1% fetal bovine serum, 1% nonessential amino acids, and 1% penicillin/streptomycin), after which 90 μL of the low-serum RPMI 1640 is added. Tesevatinib is diluted to 10 times the test concentrations and 10 μL are added to triplicate wells for a 72-h incubation. Cell viability is determined.
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• Animal Research:
  Tumor-bearing mice are given either Tesevatinib, erlotinib, or gefitinib at 100 mg/kg and tumors are harvested 1 to 72 h later. Half an hour before the respective time point, EGF (50 μg/mouse) is given via i.v. bolus injection with tumors dissected 30 min later and tumor extracts are prepared by homogenization in 10 volumes of ice-cold lysis buffer. Lysates are clarified by centrifugation and EGFR tyrosine phosphorylation levels are determined by ELISA.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

XL647, XL-647, XL 647, Vascular endothelial growth factor receptor, VEGFR, Tesevatinib, KDR, KD019, KD-019, KD 019, inhibit, Inhibitor, HER2/ErbB2, HER1, FLT4, EXEL7647, EXEL-7647, EXEL 7647, ErbB-1, ErbB2, Ephrin Receptor, EphB4, Epidermal growth factor receptor, EphrinReceptor, EGFR

Compound Identifiers

PubChem CID

10458325