CZ415   Click here for help

GtoPdb Ligand ID: 9837

Synonyms: compound 3 [PMID: 27563401] | CZ-415
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: CZ415 is a potent and selective, ATP-competitive mTOR inhibitor that has potential anti-inflammatory activity [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 87.76
Molecular weight 455.24
XLogP 3.52
No. Lipinski's rules broken 0
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Canonical SMILES CCNC(=O)Nc1ccc(cc1)c1nc(N2CCOCC2C)c2c(n1)C(C)(C)S(=C)(=C)C2
Isomeric SMILES CCNC(=O)Nc1ccc(cc1)c1nc(N2CCOC[C@@H]2C)c2c(n1)C(C)(C)S(=C)(=C)C2
InChI InChI=1S/C24H33N5O2S/c1-7-25-23(30)26-18-10-8-17(9-11-18)21-27-20-19(15-32(5,6)24(20,3)4)22(28-21)29-12-13-31-14-16(29)2/h8-11,16H,5-7,12-15H2,1-4H3,(H2,25,26,30)/t16-/m0/s1
Bioactivity Comments
CZ415 is >1000-fold selective for mTOR over other lipid kinases from the same family (i.e. phosphatidylinositide 3-kinases (PI3K) α/&beta/γ/δ and DNA-dependent protein kinase (DNAPK)) [1]. CZ415 inhibits mTORC1- and mTORC2-dependent signalling in vitro (assessed as inhibition of phosphorylation of the downstream targets S6 ribosomal protein and protein kinase B respectively) with high potency. As a therapeutic lead, CZ415 has low hERG liability (IC50 48μM).
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
mechanistic target of rapamycin kinase Primary target of this compound Hs Inhibitor Inhibition 8.1 pIC50 - 1
pIC50 8.1 (IC50 8.51x10-9 M) [1]
Description: Assessed in a competition binding assay using a mixed inhibitor lipid kinase matrix.