Tesevatinib (XL-647) is an oral, multi-targeted tyrosine kinase inhibitor with IC50 values ​​of 0.3, 16, 1.5, 8.7, and 1.4 nM for EGFR, ErbB2, KDR, Flt4, and EphB4.

EGFR:0.3 nM, FLT4:8.7 nM, KDR:1.5 nM, ErbB2:16 nM

Tesevatinib (XL-647) 有效抑制EGF/ErbB2、VEGF和ephrin RTK家族，对EGFR、ErbB2、KDR和EphB4的IC50分别为 0.3、16、1.5、8.7和 1.4 nM。[1]

方法：为了研究Tesevatinib (XL-647) 对T790M突变体EGFR的体内影响，在雌性严重联合免疫缺陷小鼠中建立H1975人肿瘤异种移植物，并每天口服一次Tesevatinib (XL-647) (剂量分别为10、30和100 mg/kg，14天)
结果：Tesevatinib (XL-647) 以剂量依赖的方式显著抑制肿瘤生长,肿瘤生长抑制率分别为33%、66%和92%.[1]
方法：Tesevatinib (XL-647)（7.5 ， 15 mg/kg，腹腔注射，每天）治疗多囊肾病的良好表征 bpk 模型小鼠，评估新生儿小鼠在出生后发育期间的疗效和毒性。
结果： Tesevatinib (XL-647) 对多种激酶级联反应的体内药理抑制降低了膀胱生成关键介质的磷酸化：EGFR、ErbB2、c-Src 和 KDR；激酶活性的降低导致ARPKD的bpk和PCK模型中肾脏和胆道疾病的显着减少。Tesevatinib (XL-647)对疾病的改善与任何明显的毒性无关。[2]

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.

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.