Details of the Drug

General Information of Drug (ID: DMVIMQX)

Drug Name
ZSTK474
Synonyms
ZSTK474; 475110-96-4; ZSTK-474; 4,4'-(6-(2-(Difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine; ZSTK 474; TCMDC-137004; UNII-K0068GK39A; CHEMBL586702; CHEBI:90545; K0068GK39A; 2-(2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine; 2-(2-Difluoromethylbenzimidazol-1-yl)-4,6-bis(morpholino)-1,3,5-triazine; AK-40326; 2-(Difluoromethyl)-1-(4,6-Dimorpholin-4-Yl-1,3,5-Triazin-2-Yl)-1h-Benzimidazole; C19H21F2N7O2; 2wxl; PubChem22461; SCHEMBL373282; QCR-72; GTPL7965; CTK8B6247; SYN1099
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [1]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 417.4
Logarithm of the Partition Coefficient (xlogp) 2.3
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 10
Chemical Identifiers
Formula
C19H21F2N7O2
IUPAC Name
4-[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]morpholine
Canonical SMILES
C1COCCN1C2=NC(=NC(=N2)N3C4=CC=CC=C4N=C3C(F)F)N5CCOCC5
InChI
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
InChIKey
HGVNLRPZOWWDKD-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11647372
ChEBI ID
CHEMBL586702
CAS Number
475110-96-4
UNII
K0068GK39A
DrugBank ID
DB12904
TTD ID
D0O1LD
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Gene/Protein Processing [3]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) OTO8JQJA PK3CB_HUMAN Gene/Protein Processing [3]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD) OTOMP6TH PK3CD_HUMAN Gene/Protein Processing [3]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Post-Translational Modifications [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
PI3-kinase gamma (PIK3CG) DTT PIK3CG 1.98E-01 -0.05 -0.55
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7965).
2 Combination of the PI3K inhibitor ZSTK474 with a PSMA-targeted immunotoxin accelerates apoptosis and regression of prostate cancer. Neoplasia. 2013 Oct;15(10):1172-83.
3 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). J Med Chem. 2011 Oct 27;54(20):7105-26. doi: 10.1021/jm200688y. Epub 2011 Sep 27.
4 The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomas. Mol Cancer Ther. 2013 Oct;12(10):1994-2005. doi: 10.1158/1535-7163.MCT-13-0206. Epub 2013 Jul 19.