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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H19ClF3NO5.C3H4O4
Molecular Weight 573.9
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Voruciclib malonate

SMILES

OC(=O)CC(O)=O.CN1CC[C@H]([C@@H]1CO)C2=C3OC(=CC(=O)C3=C(O)C=C2O)C4=CC=C(C=C4Cl)C(F)(F)F

InChI

InChIKey=OMFFALALROLOOU-OJMBIDBESA-N
InChI=1S/C22H19ClF3NO5.C3H4O4/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;4-2(5)1-3(6)7/h2-3,6-8,12,14,28-30H,4-5,9H2,1H3;1H2,(H,4,5)(H,6,7)/t12-,14+;/m1./s1

HIDE SMILES / InChI

Molecular Formula C22H19ClF3NO5
Molecular Weight 469.838
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity ( + )

Molecular Formula C3H4O4
Molecular Weight 104.0615
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.chemietek.com/voruciclib-details.aspx http://www.pharmacodia.com/yaodu/html/v1/chemicals/95276ef6535840ec6e432a7fc28688cb.html

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.

Approval Year

TargetsConditions

Conditions

PubMed

PubMed

TitleDatePubMed
Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.
2015
A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.
2016 Jul 2
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 19:16:25 GMT 2023
Edited
by admin
on Sat Dec 16 19:16:25 GMT 2023
Record UNII
ZPF5FLN7WY
Record Status Validated (UNII)
Record Version
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Name Type Language
Voruciclib malonate
Common Name English
Propanedioic acid, compd. with 2-[2-chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl]-4H-1-benzopyran-4-one (1:1)
Systematic Name English
Code System Code Type Description
FDA UNII
ZPF5FLN7WY
Created by admin on Sat Dec 16 19:16:25 GMT 2023 , Edited by admin on Sat Dec 16 19:16:25 GMT 2023
PRIMARY
CAS
2505206-37-9
Created by admin on Sat Dec 16 19:16:25 GMT 2023 , Edited by admin on Sat Dec 16 19:16:25 GMT 2023
PRIMARY
PUBCHEM
164512937
Created by admin on Sat Dec 16 19:16:25 GMT 2023 , Edited by admin on Sat Dec 16 19:16:25 GMT 2023
PRIMARY
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