AMG-548 dihydrochloride

AMG-548 dihydrochloride, an orally active and selective p38α inhibitor (Ki=0.5 nM), shows slightly selective over p38β (Ki=36 nM) and >1000 fold selective against p38γ and p38δ. AMG-548 dihydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC50=3 nM). AMG-548 dihydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε.

Product information

Molecular Weight: 534.48

Formula: C29H29Cl2N5O

Chemical Name: 2-[(2-amino-3-phenylpropyl)amino]-3-methyl-5-(naphthalen-2-yl)-6-(pyridin-4-yl)-3,4-dihydropyrimidin-4-one dihydrochloride

Smiles: Cl.Cl.CN1C(=O)C(=C(N=C1NCC(N)CC1C=CC=CC=1)C1C=CN=CC=1)C1=CC2=CC=CC=C2C=C1

InChiKey: WQZUYJOJJJERDI-UHFFFAOYSA-N

InChi: InChI=1S/C29H27N5O.2ClH/c1-34-28(35)26(24-12-11-21-9-5-6-10-23(21)18-24)27(22-13-15-31-16-14-22)33-29(34)32-19-25(30)17-20-7-3-2-4-8-20;;/h2-16,18,25H,17,19,30H2,1H3,(H,32,33);2*1H

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

AMG-548 dihydrochloride has a modest selectivity against JNK2 (Ki: 39 nM) and JNK3 (Ki: 61 nM). It is also extremely potent in the inhibition of whole blood LPS stimulated TNFa (IC50: 3 nM) and IL1b (IC50: 7 nM) as well as TNFa induced IL-8 (IC50: 0.7 nM) and IL-1b induced IL-6 (IC50: 1.3 nM) in human whole blood. AMG-548 dihydrochloride (10 μM) inhibits the hDvl2 shift .

In Vivo:

AMG-548 dihydrochloride has rat F of 62% and dog F of 47%. The t1/2 is 4.6 hours in rats and 7.3 hours in dogs.

References:

1. Lee MR, et al. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alphaprotein. Curr Med Chem. 2005;12(25):2979-94.
2. Verkaar F, et al. Inhibition of Wnt/β-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Iδ/ɛ. Chem Biol. 2011 Apr 22;18(4):485-94.

Products are for research use only. Not for human use.