LL-K9-3   Click here for help

GtoPdb Ligand ID: 12107

Compound class: Synthetic organic
Comment: LL-K9-3 is a small-molecule that induces simultaneous degradation of CDK9 and cyclin T1 (CDK9-Cyclin T1 heterodimers) that was developed for anti-tumour potential in transcriptionally addicted cancers [1]. It uses hydrophobic tagging technology (HyT) to induce polyubiquitination of CDK9-cyclin T1 complexes, as a mechanism to promote proteasome-mediated degradation of both proteins. In particular LL-K9-3 was evaluated for its inhibitory effects on CDK9 and androgen receptor-mediated signalling pathways in prostate cancer. LL-K9-3 elicits more potent anti-proliferative and pro-apoptotic effects than its parental CDK9 inhibitor BMS-387032 (a.k.a. SNS032), or than the CDK9-only PROTAC THAL-SNS-032.
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 10
Hydrogen bond donors 2
Rotatable bonds 16
Topological polar surface area 205.65
Molecular weight 683.28
XLogP 2.76
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 C[C@@H]1CC[C@H]([C@@H](C1)OCC(=O)NCCS(=O)(=O)N1CCC(CC1)C(=O)Nc1ncc(s1)SCc1ncc(o1)C(C)(C)C)C(C)C
Isomeric SMILES O=C(NCCS(=O)(=O)N1CCC(CC1)C(=O)Nc1ncc(s1)SCc1ncc(C(C)(C)C)o1)CO[C@H]1[C@H](C(C)C)CC[C@@H](C)C1
InChI InChI=1S/C31H49N5O6S3/c1-20(2)23-8-7-21(3)15-24(23)41-18-26(37)32-11-14-45(39,40)36-12-9-22(10-13-36)29(38)35-30-34-17-28(44-30)43-19-27-33-16-25(42-27)31(4,5)6/h16-17,20-24H,7-15,18-19H2,1-6H3,(H,32,37)(H,34,35,38)/t21-,23+,24-/m1/s1
InChI Key NPRIWHDFWDSJRZ-YFNKSVMNSA-N
Bioactivity Comments
The DC50 values of LL-K9-3 for CDK9 and cyclin T1 are 0.66 and 0.59 μM respectively [1]. The ligand entry for BMS-387032 (a.k.a. SNS032) provides affinity/potency data for the CDK9-directed component of LL-K9-3 across a number of CDKs.