VS-5584

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H22N8O
Molecular Weight	354.4096
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)N1C(C)=NC2=C(N=C(N=C12)N3CCOCC3)C4=CN=C(N)N=C4

InChI

InChIKey=QYBGBLQCOOISAR-UHFFFAOYSA-N

InChI=1S/C17H22N8O/c1-10(2)25-11(3)21-14-13(12-8-19-16(18)20-9-12)22-17(23-15(14)25)24-4-6-26-7-5-24/h8-10H,4-7H2,1-3H3,(H2,18,19,20)

HIDE SMILES / InChI

Molecular Formula	C17H22N8O
Molecular Weight	354.4096
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://adisinsight.springer.com/drugs/800039309
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25432176 https://www.ncbi.nlm.nih.gov/pubmed/23270925

VS-5584 is a potent and selective oral small molecule inhibitor of all 4 PI3K isoforms and mTORC1 and mTORC2. VS-5584 inhibits mTOR, PI3Kα/β/δ/γ with IC50 of 3.4 nM and 2.6-21 nM, respectively. Verastem has patent protection of VS-5584 through 2029, and has received orphan drug designation for VS-5584 in mesothelioma in the US and EU. Verastem is currently conducting a Phase 1 trial of VS-5584 in patients with advanced solid tumors and lymphomas.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23270925	Inhibitor 8297	3.4 nM [IC50]
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23270925	Inhibitor 8297	2.6 nM [IC50]
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23270925	Inhibitor 8297	2.7 nM [IC50]
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23270925	Inhibitor 8297	3.0 nM [IC50]
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23270925	Inhibitor 8297	21.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malignant mesothelioma 6 Sources: https://clinicaltrials.gov/ct2/show/NCT02372227 http://adisinsight.springer.com/drugs/800039309	Primary		Phase I 428	Unknown Approved Use Unknown
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT01991938 http://adisinsight.springer.com/drugs/800039309	Primary		Phase I 428	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000N0S	https://www.1pchem.com/search?query=1P000N0S
AChemBlock	O33811	http://www.achemblock.com/catalogsearch/result/?q=O33811
AK Scientific	2797AH	https://aksci.com/item_detail.php?cat=2797AH
Achemo Scientific Limited	AC-91307	http://www.achemo.com/search/?Keyword=AC-91307
Angene	AGN-PC-080U6M	http://www.angenechemical.com/productshow/AGN-PC-080U6M.html
ApexBio Technology	A3927	https://www.apexbt.com/catalogsearch/result/?q=A3927
AstaTech	44111	http://astatechinc.com/CPSResult.php?CRNO=44111
Cayman Chemical	16294	http://www.caymanchem.com/app/template/Product.vm/catalog/16294
Chem Scene	CS-1202	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1202
ChemShuttle	106217	https://www.chemshuttle.com/catalogsearch/result/?q=106217
Combi-Blocks	QJ-8314	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-8314
Debye Scientific	DA-46738	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-46738
Debye Scientific	DA-46740	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-46740
Excenen	EX-A288	http://www.excenen.com/searchresultlist.php?id=EX-A288
Lab Network	LN01314654	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01314654
Matrix Scientific	145551	http://www.matrixscientific.com/145551.html
MedChem Express	HY-16585	https://www.medchemexpress.com/search.html?q=HY-16585&ft=&fa=&fp=
MolPort	MolPort-035-757-944	https://www.molport.com/shop/molecule-link/MolPort-035-757-944
Molnova	M17218	https://www.molnova.com/en/serch-list.html?keywords=M17218
MuseChem	I000980	https://www.musechem.com/product/I000980.html
PI Chemicals	PI-38232	http://www.pipharm.com/catalog_products/PI-38232.html
Selleck Chemicals	S7016	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7016
ShangHai Biochempartner	BCP001004	http://www.biochempartner.com/search_BCP001004
ShangHai Biochempartner	BCP08247	http://www.biochempartner.com/search_BCP08247
TargetMol	T6103	https://www.targetmol.com/search?keyword=T6103
Toronto Research Chemicals	C178435	https://www.trc-canada.com/product-detail/?CatNum=C178435
eMolecules	45475513	https://orderbb.emolecules.com/search/#?query=45475513
eNovation Chemicals	D320276	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D320276&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7514501223	https://mcule.com/MCULE-7514501223/

PubMed

Title	Date	PubMed
VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer.	2013 Feb	23270925

Patents

Sample Use Guides

In Vivo Use Guide

Starting dose of VS-5584 will be 20mg taken once daily, 3x/week of each 21 day cycle. All subjects will also receive 2x/day treatment with 400mg VS-6063 in 21 day cycles. Number of Cycles: until progression or unacceptable toxicity develops.

Route of Administration: Oral

In Vitro Use Guide

In the FLT3-ITD harboring MV4-11 cells, VS-5584 blocks pAkt (S473) and pAkt (T308) with IC50 of 12 and 13 nM, respectively

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:04:58 UTC 2023` Edited by `admin` on `Sat Dec 16 11:04:58 UTC 2023`
Record UNII	W71J4X250V
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VS-5584

Common Name

English

5-(8-METHYL-9-(1-METHYLETHYL)-2-(4-MORPHOLINYL)-9H-PURIN-6YL)-2-PYRIMIDINAMINE

Systematic Name

English

VS 5584 [WHO-DD]

Common Name

English

2-PYRIMIDINAMINE, 5-(8-METHYL-9-(1-METHYLETHYL)-2-(4-MORPHOLINYL)-9H-PURIN-6-YL)-

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

463614