VORUCICLIB

Investigational

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 Search

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

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
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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:49:09 GMT 2025` Edited by `admin` on `Mon Mar 31 21:49:09 GMT 2025`
Record UNII	W66XP666AM
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

voruciclib [INN]

Preferred Name

English

VORUCICLIB

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 [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