ralimetinib   Click here for help

GtoPdb Ligand ID: 7959

Synonyms: LY-2228820 | LY-2228820 free base | LY2228820
PDB Ligand
Compound class: Synthetic organic
Comment: Ralimetinib was developed as a potent and selective, ATP-competitive inhibitor of p38 MAPK α and β (MAPK14 and MAPK11 respectively) [3,6]. The compound is delivered orally as the dimesylate salt (PubChem CID 11570805). It is compound 40 in Mader et al. (2008) [4].
In 2023, a report in Cell Chemical Biology demonstrated that the anticancer activity of ralimetinib is in fact due to inhibition of EGFR function, despite the compound being >30-fold less potent against EGFR than it is against p38α [1]. This study found that sensitivity of tumour cells to ralimetinib was retained when p38α and p38β genes were knocked-out, and that the EGFRT790M (gatekeeper) mutation conferred resistance to both ralimetinib and the approved EGFR inhibitor gefitinib. The cocrystal structure of ralimetinib bound to the EGFR confirmed the EGFR hypothesis.

SARS-CoV-2: p38 MAPK activity has been reported to be upregulated following SARS-CoV-2 infection of host cells in vitro. Ralimetinib produces an antiviral effect with an IC50 of 873 nM [2].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 85.41
Molecular weight 420.24
XLogP 5.63
No. Lipinski's rules broken 1
Click here for help
Canonical SMILES Fc1ccc(cc1)c1nc([nH]c1c1ccc2c(n1)n(CC(C)(C)C)c(n2)N)C(C)(C)C
Isomeric SMILES Fc1ccc(cc1)c1nc([nH]c1c1ccc2c(n1)n(CC(C)(C)C)c(n2)N)C(C)(C)C
InChI InChI=1S/C24H29FN6/c1-23(2,3)13-31-20-17(28-22(31)26)12-11-16(27-20)19-18(14-7-9-15(25)10-8-14)29-21(30-19)24(4,5)6/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30)
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
International Nonproprietary Names Click here for help
INN number INN
9753 ralimetinib
Synonyms Click here for help
LY-2228820 | LY-2228820 free base | LY2228820
Database Links Click here for help
CAS Registry No. 862505-00-8
ChEMBL Ligand CHEMBL2364626
GtoPdb PubChem SID 249565642
PubChem CID 11539025
Search Google for chemical match using the InChIKey XPPBBJCBDOEXDN-UHFFFAOYSA-N
Search Google for chemicals with the same backbone XPPBBJCBDOEXDN
Search PubMed clinical trials ralimetinib
Search PubMed titles ralimetinib
Search PubMed titles/abstracts ralimetinib
UniChem Compound Search for chemical match using the InChIKey XPPBBJCBDOEXDN-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey XPPBBJCBDOEXDN-UHFFFAOYSA-N