voruciclib   Click here for help

GtoPdb Ligand ID: 9923

Synonyms: P1446A | P1446A-05
Compound class: Synthetic organic
Comment: Voruciclib (P1446A, or P1446A-05) is an orally active, non-selective CDK inhibitor that was developed for antineoplastic potential. Potent inhibition of CDK9, 4/6 and 1 by voruciclib is considered as a novel pro-apoptotic mechanism applicable to the treatment of malignant melanoma [3] and to overcome resistance to Bcl-2 inhibition (e.g. by venetoclax) in B cell malignancies [2,4].
Use of voruciclib in combination with BRAF inhibitors for the treatment of malignant melanoma is claimed in patent US20160136132A1 [1]. Preparation of pure (+)-trans enantiomer of the compound shown here, is claimed in patent WO2007148158A1 [5].
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
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 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.

✖
Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 4
Topological polar surface area 94.14
Molecular weight 469.09
XLogP 4.88
No. Lipinski's rules broken 0
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.

✖
Canonical SMILES OCC1N(C)CCC1c1c(O)cc(c2c1oc(cc2=O)c1ccc(cc1Cl)C(F)(F)F)O
Isomeric SMILES OC[C@@H]1N(C)CC[C@H]1c1c(O)cc(c2c1oc(cc2=O)c1ccc(cc1Cl)C(F)(F)F)O
InChI InChI=1S/C22H19ClF3NO5/c1-27-5-4-12(14(27)9-28)19-15(29)7-16(30)20-17(31)8-18(32-21(19)20)11-3-2-10(6-13(11)23)22(24,25)26/h2-3,6-8,12,14,28-30H,4-5,9H2,1H3/t12-,14+/m1/s1
InChI Key MRPGRAKIAJJGMM-OCCSQVGLSA-N
Bioactivity Comments
Inhibition of kinases other than the CDKs is reported by Paiva et al. (2015) [4]. The observed in vitro inhibition of the GSK3β and PIM1 kinases does not translate to inhibition of these enzymes in CLL cells.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
cyclin dependent kinase 8 Hs Inhibitor Inhibition 7.9 pIC50 - 4
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [4]
Description: Inhibition of CDK8/cyclinC.
glycogen synthase kinase 3 alpha Hs Inhibitor Inhibition 7.8 pIC50 - 4
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [4]
cyclin dependent kinase 9 Hs Inhibitor Inhibition 7.7 pIC50 - 4
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [4]
Description: Inhibition of CDK9/cyclinT.
LIM domain kinase 1 Hs Inhibitor Inhibition 7.7 pIC50 - 4
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [4]
cyclin dependent kinase 1 Hs Inhibitor Inhibition 7.6 pIC50 - 4
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [4]
Description: Inhibition of CDK1/cyclinB
glycogen synthase kinase 3 beta Hs Inhibitor Inhibition 7.2 pIC50 - 4
⤷ pIC50 7.2 (IC50 7.1x10-8 M) [4]
Pim-1 proto-oncogene, serine/threonine kinase Hs Inhibitor Inhibition 7.1 pIC50 - 4
⤷ pIC50 7.1 (IC50 7.2x10-8 M) [4]
mitogen-activated protein kinase kinase 2 Hs Inhibitor Inhibition 7.1 pIC50 - 4
⤷ pIC50 7.1 (IC50 8.7x10-8 M) [4]
cyclin dependent kinase 4 Hs Inhibitor Inhibition 7.1 pIC50 - 4
⤷ pIC50 7.1 (IC50 9x10-8 M) [4]
Description: Inhibition of CDK4/cyclinD1.
dual specificity tyrosine phosphorylation regulated kinase 1B Hs Inhibitor Inhibition 7.0 pIC50 - 4
⤷ pIC50 7.0 (IC50 9.4x10-8 M) [4]
casein kinase 1 gamma 1 Hs Inhibitor Inhibition 7.0 pIC50 - 4
⤷ pIC50 7.0 (IC50 1.1x10-7 M) [4]
cyclin dependent kinase 2 Hs Inhibitor Inhibition 6.7 pIC50 - 4
⤷ pIC50 6.7 (IC50 1.8x10-7 M) [4]
Description: Inhibition of CDK2/cyclinA
cyclin dependent kinase 5 Hs Inhibitor Inhibition 6.7 pIC50 - 4
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [4]
Description: Inhibition of CDK5/cyclin p35 (CDK5R1).
cyclin dependent kinase 6 Hs Inhibitor Inhibition 6.7 pIC50 - 4
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [4]
Description: Inhibition of CDK6/cyclinD3.