Oritinib (SH-1028) mesylate 是一种选择性的、口服活性的、基于嘧啶的不可逆EGFR抑制剂。IC50值为18 nM。Oritinib (SH-1028) mesylate 对 EGFR 敏感和耐药 (T790 M) 突变表现出有效的活性。Oritinib (SH-1028) mesylate 显着抑制EGFR敏感和耐药突变肿瘤细胞的增殖。
| 生物活性 | Oritinib (SH-1028) mesylate is a selective, orally active, and pyrimidine-based irreversible inhibitor ofEGFRwith anIC50of 18 nM. Oritinib (SH-1028) mesylate exhibits potent activity againstEGFRsensitive and resistant (T790 M) mutations. Oritinib (SH-1028) mesylate significantly inhibits proliferation of tumor cells withEGFRsensitive and resistant mutation[1]. |
| IC50& Target[1] | EGFR (WT) 18 nM (IC50) | EGFRL858R 0.7 nM (IC50) | EGFRL861Q 4 nM (IC50) | EGFRL858R/T790M 0.1 nM (IC50) | EGFRd746-750 1.4 nM (IC50) | EGFRd746-750/T790M 0.89 nM (IC50) |
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体外研究
(In Vitro) | Oritinib (SH-1028) (72 hours; 10 μmol/L and the 3-fold dilution; nine times) mesylate selectively inhibits EGFR-mutated NCI-H1975, H3255 and PC-9 cells, withIC50values of 3.93, 9.39 and 7.63 nM, respectively, which is more sensitive than the inhibition of wild-type EGFR in A431 cells[1].
Cell Proliferation Assay[1] | Cell Line: | A431 (EGFRWT), H3255 (EGFRL858R), PC-9 (EGFRd746-750) and NCI-H1975 (EGFRL858R/T790M) cells | | Concentration: | 0.001, 0.01, 0.1, 1, and 10 μM | | Incubation Time: | 72 hours | | Result: | Selectively inhibited EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC50s of 3.93±1.12, 9.39±0.88 and 7.63±0.18 nmol/L, respectively, which were about 198-, 83- and 102-fold more sensitive than the inhibition of wild-type EGFR in A431 cells (IC50=778.89±134.74 nM). |
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体内研究
(In Vivo) | Oritinib (SH-1028) (p.o.; once daily for consecutive 14 days; 2.5-15 mg/kg) mesylate inhibits EGFR-mutant tumor progression but not wild-type EGFR in vivo[1].
Oritinib (SH-1028) (p.o.; once daily for consecutive 14 days; 2.5-15 mg/kg) mesylate only induces a moderate tumor growth inhibition in A431 (wild-type EGFR) tumor xenografts, while causes profound and sustained tumor shrinkage in both NCI-H1975 and PC-9 xenograft models with EGFR mutations with 5 mg/kg/day[1].
Oritinib (SH-1028) (p.o.; once daily for consecutive 14 days; 2.5-15 mg/kg) mesylate shows good bioavailability, and is distributed extensively from the plasma to the tissues with Tmaxof 1.5-2 h, and AUC0–tvalues of SH-1028 in plasma are 118, 300 and 931 ng × h/ml on Day 1, while 272, 308 and 993 ng × h/ml on Day 14[1].
| Animal Model: | Nu/Nu female nude mice (6-8 weeks) bearing human lung cancer cell lines[1] | | Dosage: | 2.5, 5, and 15 mg/kg (SH-1028) and control group (osimertinib, 5 mg/kg) | | Administration: | p.o.; once daily for consecutive 14 days | | Result: | Only induced a moderate tumor growth inhibition in A431 (wild-type EGFR) tumor xenografts, while caused profound and sustained tumor shrinkage in both NCI-H1975 and PC-9 xenograft models with EGFR mutations with 5 mg/kg/day. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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