CDK9 PROTAC C3   Click here for help

GtoPdb Ligand ID: 13713

Compound class: Synthetic organic
Comment: Compound C3 is an orally bioavailable CDK9 degrader. Its target-selectivity is achieved by linkage of the potent CDK9 inhibitor AT-7519, to a CRBN ligand to engage the CRL4CRBN E3 ligase [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 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.

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Hydrogen bond acceptors 15
Hydrogen bond donors 5
Rotatable bonds 14
Topological polar surface area 170.82
Molecular weight 807.77
XLogP 3.01
No. Lipinski's rules broken 3

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
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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.

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/)

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Canonical SMILES C1=CC(=CC(=C1)NC2CCC(=O)NC2=O)N3CCN(CC3)CC4CCN(CC4)CC(=O)N5CCC(CC5)NC(=O)C6=NNC=C6NC(=O)C7=C(C=CC=C7Cl)Cl
Isomeric SMILES O=C(C1=C(Cl)C=CC=C1Cl)NC2=CNN=C2C(NC3CCN(C(CN4CCC(CN5CCN(C6=CC(NC7C(NC(CC7)=O)=O)=CC=C6)CC5)CC4)=O)CC3)=O
InChI InChI=1S/C39H48Cl2N10O5/c40-29-5-2-6-30(41)35(29)38(55)45-32-22-42-47-36(32)39(56)44-26-11-15-51(16-12-26)34(53)24-48-13-9-25(10-14-48)23-49-17-19-50(20-18-49)28-4-1-3-27(21-28)43-31-7-8-33(52)46-37(31)54/h1-6,21-22,25-26,31,43H,7-20,23-24H2,(H,42,47)(H,44,56)(H,45,55)(H,46,52,54)
InChI Key RKEBQEQMPKZBRC-UHFFFAOYSA-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/)
Bioactivity Comments
CDK9 PROTAC C3 has a DC50 of 1.09 nM in a SCLC cell line [1]. It exhibits nanomaolar antiproliferative activity in SCLC cell lines in vitro, and antitumour activity in SCLC xenograft models.