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Details

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
Structure of VORUCICLIB

SMILES

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=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

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 UNSPECIFIED

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
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 Thu Jul 06 13:25:55 UTC 2023
Edited
by admin
on Thu Jul 06 13:25:55 UTC 2023
Record UNII
W66XP666AM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VORUCICLIB
INN   WHO-DD  
INN  
Official Name English
4H-1-BENZOPYRAN-4-ONE, 2-(2-CHLORO-4-(TRIFLUOROMETHYL)PHENYL)-5,7-DIHYDROXY-8-((2R,3S)-2-(HYDROXYMETHYL)-1-METHYL-3-PYRROLIDINYL)-
Systematic Name English
P-1446
Code English
voruciclib [INN]
Common Name English
Voruciclib [WHO-DD]
Common Name English
2-(2-CHLORO-4-(TRIFLUOROMETHYL)PHENYL)-5,7-DIHYDROXY-8-((2R,3S)-2-(HYDROXYMETHYL)-1-METHYLPYRROLIDIN-3-YL)-4H-1-BENZOPYRAN-4-ONE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C2185
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL3545218
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
SMS_ID
100000181775
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
PUBCHEM
67409219
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
INN
9791
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
CAS
1000023-04-0
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
NCI_THESAURUS
C141430
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
DRUG BANK
DB15157
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
FDA UNII
W66XP666AM
Created by admin on Thu Jul 06 13:25:55 UTC 2023 , Edited by admin on Thu Jul 06 13:25:55 UTC 2023
PRIMARY
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