SHP099 monohydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SHP099 是一种强效、选择性、口服生物可利用且有效的 SHP2 抑制剂。

SHP099 is a potent, selective, orally bioavailable, and efficacious SHP2 inhibitor.(In Vitro):The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC50 of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells.(In Vivo):After a single doses of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg.

The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC50 of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells.

After a single doses of 30 and 100 mg/kg , dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg.

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Metabolic Enzyme/Protease

Phosphatase

Tyrosinase|Antioxidant

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2200214-93-1

388.72

C16H20Cl3N5

>98% (HPLC)

In Vitro:?DMSO : 4.1 mg/mL (10.55 mM)

Nc1nc(N2CCC(C)(N)CC2)cnc1c1cccc(Cl)c1Cl.Cl

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(-20℃)

With Ice Pack

≥ 2 years