GDC-0575 dihydrochloride (ARRY-575 dihydrochloride) 是一种选择性的，可口服的 CHK1 抑制剂，IC₅₀ 值为 1.2 nM，具有抗肿瘤活性。

GDC-0575 dihydrochloride (ARRY-575 dihydrochloride) is an orally bioavailable CHK1 inhibitor, with an IC 50 of 1.2 nM, and has antitumor activity.

Solid

Chk1 1.2 nM (IC50)

GDC-0575 dihydrochloride is a selective and orally bioavailable CHK1 inhibitor, with an IC50 of 1.2 nM. GDC-0575 (100 nM) suppressses CHK1 activation induced by AraC by decreasing the level of Tyr15-phosphorylated CDK2. GDC-0575 (100 nM) has no effect on the viability of AML cells, but significantly reduces cell viability and induces apoptosis in combination with AraC. In addition, GDC-0575 plus AraC shows no effect on normal hematopoietic stem and progenitor cells (HSPCs). 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. has not independently confirmed the accuracy of these methods. They are for reference only.

GDC-0575 (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. Furthermore, GDC-0575 elevates the cytotoxicity of AraC in different primary AML models in vivo. GDC-0575 (25, 50 mg/kg, p.o.) dose-dependently inhibits the growth of tumor in D20 and C002 xenografts. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. 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.
[2]. Oo ZY, et al. Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors In Vivo. Clin Cancer Res. 2018 Jun 15;24(12):2901-2912.

In Vitro: DMSO : 65 mg/mL (144.06 mM; Need ultrasonic)H₂O : 25 mg/mL (55.41 mM; Need ultrasonic)配制储备液