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]
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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
UNII: S57SQE6LE5
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]

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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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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)

MEA Detail

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.