compound 25ap [PMID: 37796543]   Click here for help

GtoPdb Ligand ID: 12932

Compound class: Synthetic organic
Comment: This compund is a multitarget agent that is designed to inhibit the BRD4-LIFR-JAK1-STAT3 signalling pathway in tumour cells in which this pathway has been implicated in resistance to HDAC inhibitors [3]. The design of 25ap was based on fedratinib, which has dual JAK/BRD4 inhibitory actions [1-2]. Functionally, 25ap acts as a potent HDAC/JAK/BRD4 triple inhibitor that simultaneously elevates acetylation of histone and α-tubulin, reduces STAT3 phosphorylation and downregulates transcription of leukemia inhibitory factor receptor (LIFR), MCL1 apoptosis regulator (MCL-1), and c-Myc oncogene in breast cancer cells, which mediate antiproliferative, pro-apoptotic and anti-clonogenic effects in vitro. In vivo antitumour efficacy was demonstrated in a MDA-MB-231 breast cancer xenograft model.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 4
Rotatable bonds 10
Topological polar surface area 110.58
Molecular weight 448.52
XLogP 0.24
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES CC1=C(NC2=CC=C(C=C2)C(=O)NO)N=C(N=C1)NC3=CC=C(C=C3)OCCN4CCCC4
Isomeric SMILES ONC(C1=CC=C(NC2=NC(NC=3C=CC(=CC3)OCCN4CCCC4)=NC=C2C)C=C1)=O
InChI InChI=1S/C24H28N6O3/c1-17-16-25-24(28-22(17)26-19-6-4-18(5-7-19)23(31)29-32)27-20-8-10-21(11-9-20)33-15-14-30-12-2-3-13-30/h4-11,16,32H,2-3,12-15H2,1H3,(H,29,31)(H2,25,26,27,28)
InChI Key JUIHREVFVXLZPR-UHFFFAOYSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
N-hydroxy-4-[[5-methyl-2-[4-(2-pyrrolidin-1-ylethoxy)anilino]pyrimidin-4-yl]amino]benzamide
Database Links Click here for help
GtoPdb PubChem SID 485206053
PubChem CID 169422744
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