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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 of AMG-548

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
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
35.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

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

Patents

Sample Use Guides

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
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
  • Download
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
ACTIVE MOIETY