<Suppliers Price>

GNE-900

Names

[ CAS No. ]:
1200126-26-6

[ Name ]:
GNE-900

[Synonym ]:
3-[4-(Piperidin-1-Ylmethyl)phenyl]-9h-Pyrrolo[2,3-B:5,4-C']dipyridine-6-Carbonitrile
9H-Pyrrolo[2,3-b:5,4-c']dipyridine-6-carbonitrile, 3-[4-(1-piperidinylmethyl)phenyl]-
3-[4-(1-Piperidinylmethyl)phenyl]-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-6-carbonitrile
GNE-900

Biological Activity

[Description]:

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].

[Related Catalog]:

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

[Target]

Chk1:0.0011 μM (IC50)

Chk2:1.5 μM (IC50)


[In Vitro]

GNE-900 (1 µM; 1-48 h) 在 HT-29 细胞中与吉西他滨 (50 nM) 联合使用时，可诱导细胞凋亡并增加裂解的 PARP 的表达[1]。 Apoptosis Analysis[1] Cell Line: HT-29 cells Concentration: 1 µM Incubation Time: 1-48 h Result: Inducesd apoptosis with increased the expression of cleaved PARP when combination with gemcitabine (50 nM).

[In Vivo]

GNE-900 (2.5-40 mg/kg; p.o.; once) 与gemcitabine (HY-17026) 联用能降低肿瘤体积并增加 DNA 损伤和 γ-H2AX 的表达水平在大鼠中[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.

[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.  

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
633.4±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C23H21N5

[ Molecular Weight ]:
367.446

[ Flash Point ]:
336.9±31.5 °C

[ Exact Mass ]:
367.179688

[ LogP ]:
4.44

[ Vapour Pressure ]:
0.0±1.9 mmHg at 25°C

[ Index of Refraction ]:
1.727

Related Compounds