| Identification | Back Directory | [Name]
GNE 900 | [CAS]
1200126-26-6 | [Synonyms]
GNE 900
GNE900; GNE 900
PPYHOOZGDDPLKM-UHFFFAOYSA-N
9H-Pyrrolo[2,3-b:5,4-c']dipyridine-6-carbonitrile, 3-[4-(1-piperidinylmethyl)phenyl]- | [Molecular Formula]
C23H21N5 | [MDL Number]
MFCD28009364 | [MOL File]
1200126-26-6.mol | [Molecular Weight]
367.45 |
| Hazard Information | Back Directory | [Description]
GNE-900 is an ATP-competitive, selective, and orally bioavailable ChK1 inhibitor. In combination with chemotherapeutic agents, GNE-900 sustains ATR/ATM signaling, enhances DNA damage, and induces apoptotic cell death. GNE-900 has little single-agent activity in the absence of chemotherapy and does not grossly potentiate the cytotoxicity of gemcitabine in normal bone marrow cells. In vivo scheduling studies show that optimal administration of the ChK1 inhibitor requires a defined lag between gemcitabine and GNE-900 administration. (Mol Cancer Ther; 12(10); 1968-80). | [Uses]
GNE-900 is a an ATP-competitive, selective, and orally active ChK1 inhibitor with IC50s of 0.0011, 1.5 μM for ChKl, ChK2, respectively. GNE-900 abrogates the G2-M checkpoint, enhances DNA damage, and induces Apoptosis. gemcitabine (HY-17026) and GNE-900 administration shows anti-tumor activity[1]. | [in vivo]
GNE-900 (2.5-40 mg/kg; p.o.; once) decreases the tumor volume and increases DNA damage, γ-H2AX levels when combinated with gemcitabine (HY-17026) in rats[1]. | Animal Model: | Sprague-Dawley rats (HT-29 tumor xenografts)[1] | | Dosage: | 2.5-40 mg/kg (received a dose of gemcitabine 120 mg/kg) | | Administration: | P.o.; once | | Result: | Decreased the tumor volume and resulted in significant enhancement of DNA damage, increased γ-H2AX levels. |
| [IC 50]
Chk1: 0.0011 μM (IC50); Chk2: 1.5 μM (IC50) | [References]
[1] Blackwood E, et al. Combination drug scheduling defines a "window of opportunity" for chemopotentiation of gemcitabine by an orally bioavailable, selective ChK1 inhibitor, GNE-900. Mol Cancer Ther. 2013 Oct;12(10):1968-80. DOI:10.1158/1535-7163.MCT-12-1218 |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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