GDC-0575 dihydrochloride (ARRY-575 dihydrochloride) is an orally bioavailable CHK1 inhibitor, with an IC 50 of 1.2 nM, and has antitumor activity.
In Vitro
GDC-0575 dihydrochloride is a selective and orally bioavailable CHK1 inhibitor, with an IC 50 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
