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Details

Stereochemistry ACHIRAL
Molecular Formula C19H21F2N7O2
Molecular Weight 417.4133
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZSTK-474

SMILES

c1ccc2c(c1)nc(C(F)F)n2-c3nc(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 417.4133
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Curator's Comment:: Study of glioblastoma mouse models did not reviled an increased brain penetration of ZSTK474 relative to WT mice. Another study reports that ZSTK474 reduces CNS inflammation and demyelination of EAE mice (https://www.ncbi.nlm.nih.gov/pubmed/24844601).

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: O00329
Gene ID: 5293.0
Gene Symbol: PIK3CD
Target Organism: Homo sapiens (Human)
1.8 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​Drug as victim

Drug as victim

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor.
2006 Apr 19
Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39.
2010 Apr
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
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
Patents

Sample Use Guides

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
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 Jun 25 21:29:08 UTC 2021
Edited
by admin
on Fri Jun 25 21:29:08 UTC 2021
Record UNII
K0068GK39A
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Fri Jun 25 21:29:08 UTC 2021 , Edited by admin on Fri Jun 25 21:29:08 UTC 2021
PRIMARY
FDA UNII
K0068GK39A
Created by admin on Fri Jun 25 21:29:08 UTC 2021 , Edited by admin on Fri Jun 25 21:29:08 UTC 2021
PRIMARY
CAS
475110-96-4
Created by admin on Fri Jun 25 21:29:08 UTC 2021 , Edited by admin on Fri Jun 25 21:29:08 UTC 2021
PRIMARY
DRUG BANK
DB12904
Created by admin on Fri Jun 25 21:29:08 UTC 2021 , Edited by admin on Fri Jun 25 21:29:08 UTC 2021
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PUBCHEM
11647372
Created by admin on Fri Jun 25 21:29:08 UTC 2021 , Edited by admin on Fri Jun 25 21:29:08 UTC 2021
PRIMARY
EPA CompTox
475110-96-4
Created by admin on Fri Jun 25 21:29:08 UTC 2021 , Edited by admin on Fri Jun 25 21:29:08 UTC 2021
PRIMARY
ChEMBL
CHEMBL586701
Created by admin on Fri Jun 25 21:29:08 UTC 2021 , Edited by admin on Fri Jun 25 21:29:08 UTC 2021
PRIMARY