1196541-47-5
1196541-47-5 structure
- Name: GDC-0575(ARRY-575)
- Chemical Name: GDC0575
- CAS Number: 1196541-47-5
- Molecular Formula: C16H20BrN5O
- Molecular Weight: 378.27
- Catalog: Signaling Pathways Cell Cycle/DNA Damage Checkpoint Kinase (Chk)
- Create Date: 2018-03-20 08:52:24
- Modify Date: 2024-01-04 12:46:50
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GDC-0575 (ARRY-575, RG7741) is a highly-selective oral small-molecule Chk1 inhibitor with an IC50 of 1.2 nM.
| Name | GDC0575 |
|---|---|
| Synonyms |
(R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-indol-3-yl)cyclopropanecarboxamide
GDC-0575 |
| Description | GDC-0575 (ARRY-575, RG7741) is a highly-selective oral small-molecule Chk1 inhibitor with an IC50 of 1.2 nM. |
|---|---|
| Related Catalog | |
| Target |
1.2 nM (Chk1)[1] |
| In Vitro | GDC-0575 is significantly more potent in promoting DNA damage, replication stress and cell death than V158411, LY2603618, and MK-8776 in a panel of melanoma cell lines[1]. GDC-0575 abrogates DNA damage-induced S and G2–M checkpoints, exacerbates DNA double-strand breaks and induces apoptosis in STS cells. GDC-0575 has a synergistic or additive effect together with gemcitabine[2]. CHK1 inhibitor GDC-0575 in combination with AraC enhances the killing of primary acute myeloid leukemia cells ex vivo by inducing apoptosis[3]. |
| In Vivo | GDC-0575 is active at 25 mg/kg as a single agent, but the efficacy is improved at the higher drug dose. GDC-0575 effectively blocks tumor growth in the D20 and C002 xenografts, and the effect is maintained for at least 10 days after the final dose is administered[1]. |
| Cell Assay | AML cell lines are seeded at 1×104 cells/well in 96-well plates in triplicate, and subjected to different treatment conditions. After 24 h of incubation with GDC-0575, cell proliferation is measured with the XTT Cell Proliferation Kit II[3]. |
| Animal Admin | Mice[1] Female nude BALB/c mice are injected with 2-3×106 melanoma cells in Matrigel by subcutaneous injection on the hind flank. Once tumors reach approximately 100 mm3, mice are treated with GDC-0575 (25 mg/kg, 50 mg/kg) or vehicle (0.5% w/v methylcellulose and 0.2%v/v Tween 80) by oral gavage for 3 cycles where one cycle is three consecutive days of treatment followed by four rest days. Tumor size is measured three times per week using calipers. Mice are sacrificed at up to 6 weeks after terminating the treatment or when tumor size measured >1 cm3[1]. |
| References |
| Molecular Formula | C16H20BrN5O |
|---|---|
| Molecular Weight | 378.27 |
| Storage condition | -20℃ |