| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H19ClF3NO5 |
| Molecular Weight | 469.838 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CC[C@H]([C@@H]1CO)C2=C(O)C=C(O)C3=C2OC(=CC3=O)C4=CC=C(C=C4Cl)C(F)(F)F
InChI
InChIKey=MRPGRAKIAJJGMM-OCCSQVGLSA-N
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
Voruciclib (also known as P1446A-05) is a flavone-based, potent and selective CDK 4/6 inhibitor with activity in multiple BRAF-mutant and wild type cell lines. It is currently in clinical trials in combination with BRAF inhibitor (PLX4032) to treat advanced BRAF-mutant melanoma. Voruciclib has significant inhibitory activity against cutaneous and uveal melanoma. Mechanistic studies revealed that P1446A-05 inhibits phosphorylation targets of CDK members, and induces cell cycle arrest and apoptosis irrespective of melanoma genotype or phenotype. Voruciclib Hydrochloride is in phase I clinical trials by Piramal Life Sciences for the treatment of chronic lymphocytic leukaemia and malignant melanoma.
Originator
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
In Subjects With Advanced Refractory Malignancies:
Voruciclib available as 25mg,50mg,100mg capsule. Subjects will be enrolled at at different dose levels of P1446A-05 to be taken once a day for 14 days followed by 7 days rest.This constitutes one cycle of Voruciclib. Four such cycles will be administered.
Route of Administration:
Oral
Treatment of A375 (BRAFV600E/NRASWT), SK-MEL-63 (NRASQ61K/BRAFWT), and OCM-1 (uveal) revealed increases
in both sub-G1 fractionation and G2/M arrest at 5 uM Voruciclib; both changes were statistically significant compared to DMSO-treated controls. At lower Voruciclib concentrations (e.g. 0.5 uM), there appeared to be an increase in the G1 population.
ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SALT/SOLVATE (PARENT)
