SB-431542   Click here for help

GtoPdb Ligand ID: 8216

Synonyms: compound 14 [1] | SB431542
PDB Ligand
Compound class: Synthetic organic
Comment: SB-431542 is reported as an ATP-competitive inhibitor of a group of related activin receptor-like kinases; ALK5 (TGFBR1) [1], ALK4 (ACVR1B) and ALK7 (ACVR1C) [2], which belong to the type I receptor serine/threonine kinase family. SB-431542 acts as a selective inhibitor of endogenous activin and TGFβ signalling but has no effect on bone morphogenetic protein signalling through the more divergent ALKs of the type I receptor serine/threonine kinase family.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

SB-431542 is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 103.12
Molecular weight 384.12
XLogP 3.35
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES NC(=O)c1ccc(cc1)c1[nH]c(c(n1)c1ccccn1)c1ccc2c(c1)OCO2
Isomeric SMILES NC(=O)c1ccc(cc1)c1[nH]c(c(n1)c1ccccn1)c1ccc2c(c1)OCO2
InChI InChI=1S/C22H16N4O3/c23-21(27)13-4-6-14(7-5-13)22-25-19(20(26-22)16-3-1-2-10-24-16)15-8-9-17-18(11-15)29-12-28-17/h1-11H,12H2,(H2,23,27)(H,25,26)
InChI Key FHYUGAJXYORMHI-UHFFFAOYSA-N
References
1. Callahan JF, Burgess JL, Fornwald JA, Gaster LM, Harling JD, Harrington FP, Heer J, Kwon C, Lehr R, Mathur A et al.. (2002)
Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5).
J Med Chem, 45 (5): 999-1001. [PMID:11855979]
2. Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS. (2002)
SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7.
Mol Pharmacol, 62 (1): 65-74. [PMID:12065756]
3. Li X, Wang L, Long L, Xiao J, Hu Y, Li S. (2009)
Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles as inhibitors of transforming growth factor beta type 1 receptor (ALK5).
Bioorg Med Chem Lett, 19 (16): 4868-72. [PMID:19616940]
4. Schade D, Lanier M, Willems E, Okolotowicz K, Bushway P, Wahlquist C, Gilley C, Mercola M, Cashman JR. (2012)
Synthesis and SAR of b-annulated 1,4-dihydropyridines define cardiomyogenic compounds as novel inhibitors of TGFβ signaling.
J Med Chem, 55 (22): 9946-57. [PMID:23130626]