RG7112   Click here for help

GtoPdb Ligand ID: 9599

PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: RG7112 is a clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket. In cancer cells expressing wild-type p53, this compound stabilizes it and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumour xenografts [2].

RG7112 is commercially available from our sponsors

2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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.

✖
Hydrogen bond acceptors 7
Hydrogen bond donors 0
Rotatable bonds 12
Topological polar surface area 90.9
Molecular weight 726.28
XLogP 8.45
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES CCOc1cc(ccc1C1=NC(C(N1C(=O)N1CCN(CC1)CCCS(=O)(=O)C)(C)c1ccc(cc1)Cl)(C)c1ccc(cc1)Cl)C(C)(C)C
Isomeric SMILES CCOc1cc(ccc1C1=N[C@@]([C@@](N1C(=O)N1CCN(CC1)CCCS(=O)(=O)C)(C)c1ccc(cc1)Cl)(C)c1ccc(cc1)Cl)C(C)(C)C
InChI InChI=1S/C38H48Cl2N4O4S/c1-8-48-33-26-29(36(2,3)4)14-19-32(33)34-41-37(5,27-10-15-30(39)16-11-27)38(6,28-12-17-31(40)18-13-28)44(34)35(45)43-23-21-42(22-24-43)20-9-25-49(7,46)47/h10-19,26H,8-9,20-25H2,1-7H3/t37-,38+/m0/s1
InChI Key QBGKPEROWUKSBK-QPPIDDCLSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Immunopharmacology Comments
Human macrophages integrate signals through p53 and NF-κB to drive proinflammatory cytokine induction and NF-κB is prominent in macrophage-initiated inflammatory responses. Therefore compounds activating p53, including indirectly via MMD2 as p53-activating chemotherapeutics acting upon p53-sufficient macrophages and precursor monocytes, may indirectly impact tumors lacking functional p53 [1]