Details of the Drug

General Information of Drug (ID: DMJK5CT)

Drug Name
STX-140
Synonyms
(9beta,13alpha,14beta,17alpha)-2-Methoxyestra-1,3,5(10)-Triene-3,17-Diyl Disulfamate; STX140; CHEMBL218382; 2-MeOE2bisMATE; 2-methoxyestradiol-3,17-O,O-bis-sulfamate; STX 140; 2-MeOEbisMATE; 2gd8; 2-methoxyestradiol 3,17-O,O-bis-sulfamate; 2-MbM; 2-methoxyestradiol-3,17-O,O-bis(sulfamate); SCHEMBL446846; BDBM50200936; DB08416; (9beta,17beta)-2-methoxyestra-1,3,5(10)-triene-3,17-diyl disulfamate; Estra-1,3,5(10)-triene-3,17-diol, 2-methoxy-, disulfamate, (17beta)-; 401600-86-0; Angiomates; Estrone sulphatase inhibitors, Ipsen; STX-213; STX-641; Steroid sulfatase inhibitors, Sterix Ltd; 2-MeOE2-bis MATE; 2-MeSEMATE; 2-ethyl-estradiol bis-sulfamate; 2-methoxyestradiol, Sterix; 2-methoxyestradiol-bis-sulfamate; 2-methoxyestradiol-bis-sulfamate, Sterix
Indication
Disease Entry ICD 11 Status REF
Osteoporosis FB83.0 Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 460.6
Logarithm of the Partition Coefficient (xlogp) 2.6
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 9
Chemical Identifiers
Formula
C19H28N2O7S2
IUPAC Name
[(8R,9S,13S,14S,17S)-2-methoxy-13-methyl-3-sulfamoyloxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] sulfamate
Canonical SMILES
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2OS(=O)(=O)N)CCC4=CC(=C(C=C34)OC)OS(=O)(=O)N
InChI
InChI=1S/C19H28N2O7S2/c1-19-8-7-12-13(15(19)5-6-18(19)28-30(21,24)25)4-3-11-9-17(27-29(20,22)23)16(26-2)10-14(11)12/h9-10,12-13,15,18H,3-8H2,1-2H3,(H2,20,22,23)(H2,21,24,25)/t12-,13+,15-,18-,19-/m0/s1
InChIKey
AQSNIXKAKUZPSI-SSTWWWIQSA-N
Cross-matching ID
PubChem CID
9804302
CAS Number
401600-86-0
DrugBank ID
DB08416
TTD ID
D07ZNI

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Carbonic anhydrase II (CA-II) TTANPDJ CAH2_HUMAN Inhibitor [2]
Steryl-sulfatase (STS) TTHM0R1 STS_HUMAN Inhibitor [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [4]
BH3-interacting domain death agonist (BID) OTOSHSHU BID_HUMAN Protein Interaction/Cellular Processes [5]
Carbonic anhydrase 2 (CA2) OTJRMUAG CAH2_HUMAN Gene/Protein Processing [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [4]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Gene/Protein Processing [4]
E3 ubiquitin-protein ligase XIAP OT24GP9B XIAP_HUMAN Gene/Protein Processing [4]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Gene/Protein Processing [7]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [5]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Gene/Protein Processing [8]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Gene/Protein Processing [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Osteoporosis
ICD Disease Classification FB83.0
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Steryl-sulfatase (STS) DTT STS 1.80E-38 -0.79 -1.15
Carbonic anhydrase II (CA-II) DTT CA2 7.95E-08 0.52 0.33
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT00592579) A Phase 2 Study With Panzem in Patients With Relapsed or Plateau Phase Multiple Myeloma. U.S. National Institutes of Health.
2 Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents. J Med Chem. 2008 Mar 13;51(5):1295-308.
3 2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity. J Med Chem. 2006 Dec 28;49(26):7683-96.
4 STX140 and STX641 cause apoptosis via the intrinsic mitochondrial pathway and down-regulate survivin and XIAP expression in ovarian and prostate cancer cells. Anticancer Res. 2009 Oct;29(10):3751-7.
5 2-MeOE2bisMATE induces caspase-dependent apoptosis in CAL51 breast cancer cells and overcomes resistance to TRAIL via cooperative activation of caspases. Apoptosis. 2004 May;9(3):323-32. doi: 10.1023/b:appt.0000025809.80684.bd.
6 A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140. Anticancer Res. 2008 May-Jun;28(3A):1483-91.
7 STX140 is efficacious in vitro and in vivo in taxane-resistant breast carcinoma cells. Clin Cancer Res. 2008 Jan 15;14(2):597-606. doi: 10.1158/1078-0432.CCR-07-1717.
8 In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol. Br J Cancer. 2007 May 7;96(9):1368-76. doi: 10.1038/sj.bjc.6603727. Epub 2007 Apr 10.