1258292-64-6

1258292-64-6 structure

Name: GDC-046
Chemical Name: 2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide
CAS Number: 1258292-64-6
Molecular Formula: C₁₆H₁₃Cl₂N₃O₂
Molecular Weight: 350.199
Catalog: Signaling Pathways Epigenetics JAK
Create Date: 2018-06-24 20:12:16
Modify Date: 2024-01-10 12:42:15
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].

Name	2,6-dichloro-N-(2-(cyclopropanecarboxamido)pyridin-4-yl)benzamide
Synonyms	2,6-Dichloro-N-{2-[(cyclopropylcarbonyl)amino]-4-pyridinyl}benzamide Benzamide, 2,6-dichloro-N-[2-[(cyclopropylcarbonyl)amino]-4-pyridinyl]- GDC046

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].
Related Catalog	Signaling Pathways >> JAK/STAT Signaling >> JAK Signaling Pathways >> Epigenetics >> JAK Signaling Pathways >> Stem Cell/Wnt >> JAK Research Areas >> Inflammation/Immunology
Target	Tyk2:4.8 nM (Ki) JAK1:0.7 nM (Ki) JAK2:0.7 nM (Ki) JAK3:0.4 nM (Ki)
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].
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].
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.