| Description |
SH-1028 (mesylate) is a selective and oral active inhibitor of EGFR with an IC50 of 18 nM. SH-1028 (mesylate) exhibits potent activity against EGFR sensitive and resistant (T790 M) mutations. SH-1028 (mesylate) significantly inhibits proliferation of tumor cells with EGFR sensitive and resistant mutation[1].
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| Related Catalog |
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| Target |
18 nM (EGFR)[1]
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| In Vitro |
SH-1028 (mesylate) (72 hours; 10 μmol/L and the 3-fold dilution; nine times) selectively inhibits EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC50 values of 3.93, 9.39 and 7.63 nmol/L, respectively, which is more sensitive than the inhibition of wild-type EGFR in A431 cells[1]. Cell Viability Assay[1] Cell Line: NCI-H1975, H3255, A431, and PC-9 cells Concentration: 10 μmol/L and the 3-fold dilution; nine times Incubation Time: 72 hours Result: Selectively inhibited EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC50 values of 3.93, 9.39 and 7.63 nmol/L, respectively.
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| In Vivo |
SH-1028 (mesylate) (p.o.; once daily for consecutive 14 days; 2.5-15 mg/kg) inhibits EGFR-mutant tumor progression but not wild-type EGFR In Vivo[1]. SH-1028 (mesylate) (p.o.; once daily for consecutive 14 days; 2.5-15 mg/kg) 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]. SH-1028 (mesylate) (p.o.; once daily for consecutive 14 days; 2.5-15 mg/kg) Shows Good Bioavailability, and is Distributed Extensively From the Plasma to the Tissues with Tmax of 1.5-2 h, and AUC0–t values 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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| References |
[1]. Han L, et al. SH-1028, An Irreversible Third-Generation EGFR TKI, Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer. Front Pharmacol. 2021;12:665253.
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