AMG-548

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H27N5O
Molecular Weight	461.5576
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)C(C2=CC=C3C=CC=CC3=C2)=C(N=C1NC[C@@H](N)CC4=CC=CC=C4)C5=CC=NC=C5

InChI

InChIKey=RQVKVJIRFKVPBF-VWLOTQADSA-N

InChI=1S/C29H27N5O/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)/t25-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C29H27N5O
Molecular Weight	461.5576
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21513885 | http://adisinsight.springer.com/drugs/800019881
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16022178 https://www.ncbi.nlm.nih.gov/pubmed/20510239

AMG-548 is a selective and efficacious p38alpha inhibitor (Ki value is 0.5nM). Displays >1000-fold selectivity against 36 other kinases; inhibits whole blood LPS-stimulated TNFα (IC50 = 3 nM). Efficacious in acute and chronic models of arthritis. Clinical development of AMG-548 was terminated because of liver toxicity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
MAP kinase p38 alpha 35 Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16022178 \| https://www.ncbi.nlm.nih.gov/pubmed/19928858	Inhibitor 8297		35.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: http://adisinsight.springer.com/drugs/800019881	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
p38 MAP kinase inhibitors: many are made, but few are chosen.	2005 Jul	16022178
Inhibition of Wnt/β-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Iδ/ɛ.	2011 Apr 22	21513885

Patents

Sample Use Guides

In Vivo Use Guide

The dose of AMG-548 can be from 0.1 mg to 1000 mg/day, preferably between 1 and 500 mg/day by oral administration.

Route of Administration: Oral

In Vitro Use Guide

AMG-548 inhibited the Wnt-3a-induced hDvl2 mobility shift in U2OS-EFC cells at 10 uM

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:33:33 GMT 2023` Edited by `admin` on `Sat Dec 16 08:33:33 GMT 2023`
Record UNII	PGR0H531I4
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMG-548

Common Name

English

4(3H)-PYRIMIDINONE, 2-(((2S)-2-AMINO-3-PHENYLPROPYL)AMINO)-3-METHYL-5-(2-NAPHTHALENYL)-6-(4-PYRIDINYL)-

Systematic Name

English

Code System Code Type Description

CAS

864249-60-5

Created by admin on Sat Dec 16 08:33:34 GMT 2023 , Edited by admin on Sat Dec 16 08:33:34 GMT 2023

PRIMARY

PUBCHEM

11167112

Created by admin on Sat Dec 16 08:33:34 GMT 2023 , Edited by admin on Sat Dec 16 08:33:34 GMT 2023

PRIMARY

FDA UNII

PGR0H531I4

Created by admin on Sat Dec 16 08:33:34 GMT 2023 , Edited by admin on Sat Dec 16 08:33:34 GMT 2023

PRIMARY

ChEMBL

CHEMBL585902

Created by admin on Sat Dec 16 08:33:34 GMT 2023 , Edited by admin on Sat Dec 16 08:33:34 GMT 2023

PRIMARY

Related Record Type Details


					PGR0H531I4

AMG-548

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21513885 | http://adisinsight.springer.com/drugs/800019881Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16022178 https://www.ncbi.nlm.nih.gov/pubmed/20510239

Originator

Approval Year

Targets

Conditions

Approved Use

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21513885 | http://adisinsight.springer.com/drugs/800019881
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16022178 https://www.ncbi.nlm.nih.gov/pubmed/20510239