Voruciclib malonate

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=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
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 19 Target ID: CHEMBL3116 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603	Inhibitor 8297
Cyclin-dependent kinase 4 22 Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603	Inhibitor 8297
Cyclin-dependent kinase 6 12 Target ID: CHEMBL2508 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26810603	Inhibitor 8297

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 428	Unknown Approved Use Unknown
Relapsed/refractory chronic lymphocytic leukemia 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02117336	Primary	Phase I 428	Unknown Approved Use Unknown
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT00772876	Primary	Phase I 428	Unknown Approved Use 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
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=
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
Molcore	MC34006	http://www.molcore.com/CatMC34006.html
MuseChem	I010046	https://www.musechem.com/product/I010046.html
Toronto Research Chemicals	B690038	https://www.trc-canada.com/product-detail/?CatNum=B690038
eMolecules	89940571	https://orderbb.emolecules.com/search/#?query=89940571
mcule	MCULE-3034986781	https://mcule.com/MCULE-3034986781/

PubMed

Title	Date	PubMed
Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.	2015	26606677
A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.	2016 Jul 2	26810603

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 `Sat Dec 16 19:16:25 UTC 2023` Edited by `admin` on `Sat Dec 16 19:16:25 UTC 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 UTC 2023 , Edited by admin on Sat Dec 16 19:16:25 UTC 2023

PRIMARY

CAS

2505206-37-9

Created by admin on Sat Dec 16 19:16:25 UTC 2023 , Edited by admin on Sat Dec 16 19:16:25 UTC 2023

PRIMARY

PUBCHEM

164512937

Created by admin on Sat Dec 16 19:16:25 UTC 2023 , Edited by admin on Sat Dec 16 19:16:25 UTC 2023

PRIMARY

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Amount:

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

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