RIPK1 inhibitor 22b   Click here for help

GtoPdb Ligand ID: 10155

Synonyms: compound 22b [PMID: 30480444]
Compound class: Synthetic organic
Comment: Compound 22b represents a novel chemical scaffold class for receptor-interacting protein kinase 1 (RIPK1) inhibitors [1]. It has shown anti-metastasis activity in the experimental B16 melanoma lung metastasis model. The molecular mechanism underlying this effect is identified as inhibition of tumour-dependent RIPK1-induced programmed necrosis (necroptosis) of vascular endothelial cells, which facilitates tumour cell extravasation and metastasis. Compound 22b is a type II kinase inhibitor that interacts with the inactive conformation (DFG-out) of the RIPK1 kinase domain.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 86.27
Molecular weight 481.17
XLogP 5.04
No. Lipinski's rules broken 1
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Canonical SMILES CCn1cc(c2c1ncnc2N)c1ccc2c(c1)CCN2C(=O)Cc1cccc(c1)OC(F)(F)F
Isomeric SMILES CCn1cc(c2c1ncnc2N)c1ccc2c(c1)CCN2C(=O)Cc1cccc(c1)OC(F)(F)F
InChI InChI=1S/C25H22F3N5O2/c1-2-32-13-19(22-23(29)30-14-31-24(22)32)16-6-7-20-17(12-16)8-9-33(20)21(34)11-15-4-3-5-18(10-15)35-25(26,27)28/h3-7,10,12-14H,2,8-9,11H2,1H3,(H2,29,30,31)
1. Li Y, Xiong Y, Zhang G, Zhang L, Yang W, Yang J, Huang L, Qiao Z, Miao Z, Lin G et al.. (2018)
Identification of 5-(2,3-Dihydro-1 H-indol-5-yl)-7 H-pyrrolo[2,3- d]pyrimidin-4-amine Derivatives as a New Class of Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors, Which Showed Potent Activity in a Tumor Metastasis Model.
J Med Chem, 61 (24): 11398-11414. [PMID:30480444]