| Identification | Back Directory | [Name]
G-5555 | [CAS]
1648863-90-4 | [Synonyms]
G-5555
G5555;G 5555
8-(((2r,5r)-5-Amino-1,3-dioxan-2-yl)methyl)-6-(2-chloro-4-(6-methylpyridin-2-yl)phenyl)-2-(met
8-[(trans-5-Amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one
Pyrido[2,3-d]pyrimidin-7(8H)-one, 8-[(trans-5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)- | [Molecular Formula]
C25H25ClN6O3 | [MDL Number]
MFCD28506227 | [MOL File]
1648863-90-4.mol | [Molecular Weight]
492.96 |
| Chemical Properties | Back Directory | [Boiling point ]
684.6±65.0 °C(Predicted) | [density ]
1.363±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 25 mg/ml; DMSO: 25 mg/ml; DMSO:PBS(pH 7.2) (1:4): 0.20 mg/ml | [form ]
A crystalline solid | [pka]
6.86±0.40(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Description]
G-5555 is an inhibitor of p21-activated kinase 1 (PAK1; Ki = 3.7 nM), a non-receptor serine/threonine kinase involved in tumorigenesis. It is selective for PAK1 over the majority of targets in a panel of 235 kinases but does inhibit PAK2, PAK3, KHS1, LCK, MST3, MST4, SIK2, and YSK1 by greater than 70% with IC50 values ranging from 9 to 52 nM. G-5555 inhibits phosphorylation of MEK, a downstream target of PAK1, in EBC1 cells (IC50 = 69 nM). G-5555 (10, 20, and 30 mg/kg) dose-dependently reduces phosphorylation of MEK in tumors from an H292 non-small cell lung cancer (NSCLC) mouse xenograft model. G-5555 inhibits hERG channels less than 50% at a concentration of 10 μM, indicating the potential for a low risk of QT interval prolongation and potentially fatal arrhythmias. | [Uses]
G 5555 is a high affinity group 1 p21-activated kinases (PAK) inhibitor. | [in vivo]
G-5555 exhibits low blood clearance and an acceptable half-life. Good oral exposure (AUC = 30 μM h) and high oral bioavailability (F = 80%) are achieved[1]. In an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice, G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 and, when administered at an oral dose of 25 mg/kg b.i.d., imparts 60% tumor growth inhibition in this model and a PAK1 amplified breast cancer xenograft model, MDAMB-175[2]. | [IC 50]
PAK1: 3.7 nM (Ki); PAK2: 11 nM (Ki) | [storage]
Store at -20°C | [References]
[1] CHUDI O. NDUBAKU*. Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pKa Polar Moiety[J]. ACS Medicinal Chemistry Letters, 2015, 6 12: 1241-1246. DOI: 10.1021/acsmedchemlett.5b00398
[2] RODOLPHO C BRAGA. Tuning HERG out: antitarget QSAR models for drug development.[J]. Current topics in medicinal chemistry, 2014: 1399-1415. DOI: 10.2174/1568026614666140506124442 |
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