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].
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2D Structure
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Physico-chemical Properties
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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
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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
1. Agarwal V, Periyasamy G, Rathos M, Srivastava A, Srinivasa S. (2016)
Patent number: US20160136132. Assignee: PIRAMAL ENTERPRISES LIMITED. Priority date: 11/07/2011. Publication date: 19/05/2016.
2. Dey J, Deckwerth TL, Kerwin WS, Casalini JR, Merrell AJ, Grenley MO, Burns C, Ditzler SH, Dixon CP, Beirne E et al.. (2017)
Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition.
Sci Rep, 7 (1): 18007. [PMID:29269870]
3. Eliades P, Miller DM, Miao B, Kumar R, Taylor M, Buch S, Srinivasa SP, Flaherty KT, Tsao H. (2016)
A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.
Cancer Biol Ther, 17 (7): 778-84. [PMID:26810603]
4. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015)
Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.
PLoS ONE, 10 (11): e0143685. [PMID:26606677]
5. Sivakumar M, Mascarenhas M, Sarde A, Jadhav PK, Shukla M, Joshi K, Rathos M. (2007)
Enantiomerically pure flavone derivatives for the treatment of poliferative disorders and processes for their preparation.
Patent number: WO2007148158A1. Assignee: Piramal Life Sciences Limited. Priority date: 21/06/2006. Publication date: 27/12/2007.