Voruciclib malonate

Investigational

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 Search

SMILES

OC(=O)CC(O)=O.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=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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclin-dependent kinase 9 24 Target ID: CHEMBL3116 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603	Inhibitor 8504
Cyclin-dependent kinase 4 26 Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603	Inhibitor 8504
Cyclin-dependent kinase 6 16 Target ID: CHEMBL2508 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Advanced or inoperable malignant melanoma with BRAF mutation 3 Sources: https://clinicaltrials.gov/ct2/show/NCT01841463	Primary	Phase I 438	Unknown Approved Use Unknown
Relapsed/refractory chronic lymphocytic leukemia 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02117336	Primary	Phase I 438	Unknown Approved Use Unknown
Cancer 609 Sources: https://clinicaltrials.gov/ct2/show/NCT00772876	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
512 ng/mL EXPERIMENT https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3013	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:		VORUCICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
796 ng/mL EXPERIMENT https://ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.9076	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered: VEMURAFENIB	VEMURAFENIB	VORUCICLIB unknown	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
16700 ng × h/mL EXPERIMENT https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3013	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:		VORUCICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
14451 ng × h/mL EXPERIMENT https://ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.9076	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered: VEMURAFENIB	VEMURAFENIB	VORUCICLIB unknown	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
24 h REVIEW https://www.biospace.com/mei-pharma-reports-clinical-data-on-oral-cdk9-inhibitor-voruciclib-at-ash2023	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VORUCICLIB plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
21 h EXPERIMENT https://ascopubs.org/doi/abs/10.1200/jco.2012.30.15_suppl.3011	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VORUCICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34006	https://www.001chemical.com/chem/search?q=DY34006
AstaTech	40984	http://astatechinc.com/CPSResult.php?CRNO=40984
Chem Scene	CS-0011273	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0011273
Chem Scene	CS-0016536	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0016536
ChemShuttle	169650	https://www.chemshuttle.com/catalogsearch/result/?q=169650
eMolecules	89940571	https://orderbb.emolecules.com/search/#?query=89940571
mcule	MCULE-3034986781	https://mcule.com/MCULE-3034986781/
MedChem Express	HY-12422	https://www.medchemexpress.com/search.html?q=HY-12422&ft=&fa=&fp=
MedChem Express	HY-12422A	https://www.medchemexpress.com/search.html?q=HY-12422A&ft=&fa=&fp=
Molcore	MC34006	http://www.molcore.com/CatMC34006.html
MolPort	MolPort-046-836-607	https://www.molport.com/shop/molecule-link/MolPort-046-836-607
MolPort	MolPort-046-857-307	https://www.molport.com/shop/molecule-link/MolPort-046-857-307
MuseChem	I010046	https://www.musechem.com/product/I010046.html
Toronto Research Chemicals	B690038	https://www.trc-canada.com/product-detail/?CatNum=B690038

PubMed

Title	Date	PubMed
A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.	2016-07-02	26810603
Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.	2015	26606677

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

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)

Preferred Name

English

Code System Code Type Description

FDA UNII

ZPF5FLN7WY

Created by admin on Wed Apr 02 14:33:46 GMT 2025 , Edited by admin on Wed Apr 02 14:33:46 GMT 2025

PRIMARY

CAS

2505206-37-9

Created by admin on Wed Apr 02 14:33:46 GMT 2025 , Edited by admin on Wed Apr 02 14:33:46 GMT 2025

PRIMARY

PUBCHEM

164512937

Created by admin on Wed Apr 02 14:33:46 GMT 2025 , Edited by admin on Wed Apr 02 14:33:46 GMT 2025

PRIMARY

ACTIVE MOIETY


					W66XP666AM

VORUCICLIB

SUBSTANCE RECORD


					ZPF5FLN7WY

Voruciclib malonate

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/26810603Curator'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

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603
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

C_max

T_1/2