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GDC-0575

Names

[ CAS No. ]:
1196504-54-7

[ Name ]:
GDC-0575

Biological Activity

[Description]:

GDC0575 (ARRY-575) hydrochloride is a highly-selective and orally active Chk1 (IC50=1.2 nM) inhibitor. GDC0575 (ARRY-575) hydrochloride can be used for colitis-associated cancer (CAC) and colitis research[1].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Cell Cycle/DNA Damage >> Checkpoint Kinase (Chk)
Research Areas >> Inflammation/Immunology

[Target]

Chk1:1.2 nM (IC50)


[In Vitro]

GDC-0575 dihydrochloride 是一种选择性的具有口服活性的 CHK1 抑制剂，IC50为 1.2 nM。GDC-0575 (100 nM) 通过降低 tyr15 磷酸化 CDK2 水平抑制 AraC 诱导的 CHK1 激活[1]. GDC-0575 dihydrochloride (100 nM) 对 AML 细胞活力无影响，但与 AraC 联合使用可显著降低细胞活力，诱导细胞凋亡。GDC-0575 dihydrochloride 加 AraC 对正常造血干细胞 (HSPCs) 无影响[1]。GDC-0575 dihydrochloride 对 20 种黑色素瘤细胞系显示出细胞毒活性，但一些作为肿瘤球 (TS) 生长的细胞系相对不敏感[2]。

[In Vivo]

GDC-0575 dihydrochloride (7.5 mg/kg, p.o.) 联合 AraC 几乎可以完全消除移植 U937-Luc 细胞小鼠的白血病负担，并且比单独使用 AraC 更有效。GDC-0575 dihydrochloride 在体内不同原发性 AML 模型中提高 AraC 的细胞毒性[1]. GDC-0575 dihydrochloride (25、50 mg/kg, p.o.) 对 D20 和 C002 异种移植物肿瘤生长的剂量依赖性抑制作用[2].

[References]

[1]. Oo ZY, et al. Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors In Vivo. Clin Cancer Res. 2018 Mar 13.  

[2].  Laroche-Clary A, et al. CHK1 inhibition in soft-tissue sarcomas: biological and clinical implications. Ann Oncol. 2018 Apr 1;29(4):1023-1029.  

[3].  Di Tullio A, et al. The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukemia. Nat Commun. 2017 Nov 22;8(1):1679.  

Chemical & Physical Properties

[ Molecular Formula ]:
C16H21BrClN5O

[ Molecular Weight ]:
414.73

[ Storage condition ]:
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Related Compounds