ZSTK-474

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H21F2N7O2
Molecular Weight	417.4125
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)C1=NC2=C(C=CC=C2)N1C3=NC(=NC(=N3)N4CCOCC4)N5CCOCC5

InChI

InChIKey=HGVNLRPZOWWDKD-UHFFFAOYSA-N

InChI=1S/C19H21F2N7O2/c20-15(21)16-22-13-3-1-2-4-14(13)28(16)19-24-17(26-5-9-29-10-6-26)23-18(25-19)27-7-11-30-12-8-27/h1-4,15H,5-12H2

HIDE SMILES / InChI

Molecular Formula	C19H21F2N7O2
Molecular Weight	417.4125
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/?term=16622124
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22349137; https://www.ncbi.nlm.nih.gov/pubmed/23812078

ZSTK474 is a new PI3K inhibitor with strong antitumor activity against human cancer xenografts without toxic effects in critical organs. Specifically, ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms. ZSTK474 blocks VEGF-induced cell migration and the tube formation in human umbilical vein endothelial cells (HUVECs), and inhibits the expression of HIF-1α and secretion of VEGF in RXF-631L cells, exhibiting potent in vitro antiangiogenic activity. ZSTK474 demonstrated prophylactic efficacy in a rat model of rheumatoid arthritis (RA) through inhibition of T cell and FLS functions.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 9 Target ID: O00329 Gene ID: 5293.0 Gene Symbol: PIK3CD Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17711503	Inhibitor 8297		1.8 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT01280487	Primary		Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 BCRP 561

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677420	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677420	yes [IC50 1.6933 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677420	yes [IC50 7.5637 uM]
BCRP 773	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/28912036/	yes
MRP1 172	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/28388564/	yes
P-gp 1650	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/28388564/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27553832/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27553832/	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00DBOJ	https://www.1pchem.com/search?query=1P00DBOJ
A2B Chem	AG20867	http://a2bchem.com/prod/AG20867
AChemBlock	L14966	http://www.achemblock.com/catalogsearch/result/?q=L14966
AK Scientific	X7419	https://aksci.com/item_detail.php?cat=X7419
ApexBio Technology	A8248	https://www.apexbt.com/catalogsearch/result/?q=A8248
AstaTech	F15198	http://astatechinc.com/CPSResult.php?CRNO=F15198
BOC Sciences	475110-96-4	http://www.bocsci.com/description.asp?cas=475110-96-4
Capot Chemical	22461	https://www.capotchem.com/search.do?q=22461
Cayman Chemical	17381	http://www.caymanchem.com/app/template/Product.vm/catalog/17381
Chem Scene	CS-0083	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0083
ChemShuttle	111401	https://www.chemshuttle.com/catalogsearch/result/?q=111401
Excenen	EX-A2207	http://www.excenen.com/searchresultlist.php?id=EX-A2207
Exclusive Chemistry	2321	http://www.exchemistry.com/chem-catalog/product-2321.html
Fluorochem	50801	http://www.fluorochem.co.uk/Products/Product?code=050801
Frontier Scientific Services	500071889	http://orders.frontierssi.com/fssionline32/public/product.aspx?cat=500071889&type=hts
Hairui	HR113447	http://www.hairuichem.com/en/product/search.do?q=HR113447
KeyOrganics	AS-16245	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16245
Lab Seeker	SC-27986	http://www.labseeker.com/search.php?keywords=SC-27986&category=0
LabSeeker	SC-27986	http://www.labseeker.com/search.php?keywords=SC-27986&category=0
Matrix Scientific	147052	http://www.matrixscientific.com/147052.html
MedChem Express	HY-50847	https://www.medchemexpress.com/search.html?q=HY-50847&ft=&fa=&fp=
MolPort	MolPort-009-199-495	https://www.molport.com/shop/molecule-link/MolPort-009-199-495
Molnova	M14579	https://www.molnova.com/en/serch-list.html?keywords=M14579
MuseChem	I003653	https://www.musechem.com/product/I003653.html
ShangHai Biochempartner	BCP000158	http://www.biochempartner.com/search_BCP000158
ShangHai Biochempartner	BCP01867	http://www.biochempartner.com/search_BCP01867
TargetMol	T6168	https://www.targetmol.com/search?keyword=T6168
eMolecules	31239746	https://orderbb.emolecules.com/search/#?query=31239746
eNovation Chemicals	D572897	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D572897&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-8167619360	https://mcule.com/MCULE-8167619360/

PubMed

Title	Date	PubMed
Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor.	2006 Apr 19	16622124
Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39.	2010 Apr	20129775
Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo.	2011 Jun	21352422
Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474).	2011 Oct 27	21882832

Patents

Sample Use Guides

In Vivo Use Guide

ZSTK474 at 100, 200, or 400 mg/kg of mice body weight was orally administered daily from days 0 to 13.

Route of Administration: Oral

In Vitro Use Guide

Human prostate cancer PC3 cells growth inhibition was determined using the WST-8 assay kit. One hundred uL of cells (6 × 104 cells/mL) was seeded in 96-well plate and incubated at 37 °C. Twenty four hours later, 0.5 uL of various stock solutions of ZSTK474 was added. After further incubation for 48 h, 10 uL of WST-8 was added to each well and the cells were further incubated at 37 °C. Three hours later, the absorbances at 450 nm were measured with a microplate spectrophotometer.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:50:58 GMT 2023` Edited by `admin` on `Fri Dec 15 19:50:58 GMT 2023`
Record UNII	K0068GK39A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZSTK-474

Common Name

English

ZSTK474

Common Name

English

2-(2-DIFLUOROMETHYLBENZIMIDAZOL-1-YL)-4,6-BIS(MORPHOLINO)-1,3,5-TRIAZINE

Systematic Name

English

GNF-PF-5468

Code

English

Code System Code Type Description

NCI_THESAURUS

C95723