Example 4 [WO2017202275A1]   Click here for help

GtoPdb Ligand ID: 10449

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Example 4 is a highly potent, small-molecule inhibitor of the PD-1/PD-L1 interaction that is claimed in patent WO2017202275A1 [1].
2D Structure
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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.

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Physico-chemical Properties
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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.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 95.68
Molecular weight 645.1
XLogP 5.13
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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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.

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Canonical SMILES N#Cc1nccc(c1)COc1cc(OCc2cccc(c2Br)c2ccccc2)c(cc1CN1CCCCC1C(=O)O)Cl
Isomeric SMILES N#Cc1nccc(c1)COc1cc(OCc2cccc(c2Br)c2ccccc2)c(cc1CN1CCCC[C@H]1C(=O)O)Cl
InChI InChI=1S/C33H29BrClN3O4/c34-32-24(9-6-10-27(32)23-7-2-1-3-8-23)21-42-31-17-30(41-20-22-12-13-37-26(15-22)18-36)25(16-28(31)35)19-38-14-5-4-11-29(38)33(39)40/h1-3,6-10,12-13,15-17,29H,4-5,11,14,19-21H2,(H,39,40)/t29-/m0/s1
InChI Key YYAPLXNCTNGBJO-LJAQVGFWSA-N
Bioactivity Comments
Example 4 inhibits the PD-1/PD-L1 interaction in vitro in the femtomolar range; IC50 8 x 10-14 M in the proprietary Cisbio HTRF PD-1/PD-L1 binding assay [1]. It can also partially restore IFNγ release from PBMC expressing PD-1 in the presence of PD-L1. The compound exhibits promising in vivo anti-tumour activity in preclinical xenograft models of a number of solid tumour types.
Selectivity at ligand targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
programmed cell death 1 ligand 1 Hs None Binding - - - 1
⤷ [1]