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GDC0575 hydrochloride

CAS No. : 1196504-54-7

MCE 站：GDC0575 hydrochloride

产品活性：GDC0575 (ARRY-575) hydrochloride 是一种高选择性、口服活性的 Chk1 (IC₅₀=1.2 nM) 抑制剂。GDC0575 (ARRY-575) hydrochloride 可用于结肠炎相关癌症 CAC 和结肠炎研究。

研究领域：Cell Cycle/DNA Damage

作用靶点：Checkpoint Kinase (Chk)

In Vitro: GDC-0575 dihydrochloride is a selective ａnd orally bioavailable CHK1 inhibitor, with an IC₅₀of 1.2 nM. GDC-0575 (100 nM) suppressses CHK1 activation induced by AraC by decreasing the level of Tyr15-phosphorylated CDK2.
GDC-0575 dihydrochloride (100 nM) has no effect on the viability of AML cells, but significantly reduces cell viability ａnd induces apoptosis in combination with AraC. GDC-0575 plus AraC shows no effect on normal hematopoietic stem ａnd progenitor cells (HSPCs)[1]. GDC-0575 shows cytotoxic activity against most of 20 melanoma cell lines tested, but several cell lines grown as tumour sphere (TS) are relatively insensitive.

In Vivo: GDC-0575 dihydrochloride (7.5 mg/kg, p.o.) in combination with AraC alomost completely eradicates leukemic burden in mice transplanted with U937-Luc cells, ａnd shows more efficient activity than AraC alone. GDC-0575 dihydrochloride elevates the cytotoxicity of AraC in different primary AML models in vivo.
GDC-0575 dihydrochloride (25, 50 mg/kg, p.o.) dose-dependently inhibits the growth of tumor in D20 ａnd C002 xenografts.

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