GDC046

Cas No.:	1258292-64-6
Synonyms:	GDC-046,GDC 046
SMILES:	C1CC1C(=O)NC2=NC=CC(=C2)NC(=O)C3=C(C=CC=C3Cl)Cl
Formula:	C16H13Cl2N3O2
M.Wt:	350.2
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	GDC-046 is a potent, selective, and orally bioavailable TYK2 inhibitor with Kis of 4.8, 0.7, 0.7, and 0.4 nM for TYK2, JAK1, JAK2, and JAK3, respectively[1].
Target:	Tyk2:4.8 nM (Ki) JAK1:0.7 nM (Ki) JAK2:0.7 nM (Ki) JAK3:0.4 nM (Ki)
In Vivo:	In mice, GDC-046 exhibits relatively high clearance (65 mL/min/kg) when dosed intravenously (i.v. 1 mg/kg) and exhibits modest oral exposure (AUC=2.6 μM·h at p.o. 5 mg/kg)[1].
In Vitro:	In cell-based assays, GDC-046 demonstrates reasonable potency in blocking the IL-12 pathway (IL-12 pSTAT4 EC50=380 nM) while displaying less activity in the EPO (JAK2) pathway (EPO pSTAT5 EC50=1700 nM) and IL-6 (JAK1) pathway (IL-6 pSTAT3 EC50=2000 nM)[1].
References:	[1]. Jun Liang, et al. Lead Optimization of a 4-aminopyridine Benzamide Scaffold to Identify Potent, Selective, and Orally Bioavailable TYK2 Inhibitors. J Med Chem. 2013 Jun 13;56(11):4521-36