Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMGBPME)

• Drug Name: 2-Methoxyestradiol Drug Info
• Synonyms: ESM; Panzem; PulmoLAR; Panzem NCD; M 6383; (17beta)-2-Methoxyestra-1,3,5(10)-triene-3,17-diol; (17beta)-2-methoxyestra-1(10),2,4-triene-3,17-diol; (8R,9S,13S,14S,17S)-2-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol; 1,3,5(10)-ESTRATRIEN-2,3,17-BETA-TRIOL 2-METHYL ETHER; 1,3,5(10)-Estratriene-2,3,17-triol 2-methyl ether; 2,3,17beta-Trihydroxy-1,3,5(10)-estratriene 2-methyl ether; 2-Hydroxyestradiol 2-methyl ether; 2-Hydroxyestradol 2-methyl ether; 2-ME2, 2-Methoxyestradiol; 2-Methoxyestra-1,3,5(10)-triene-3,17beta-diol; 2-Methoxyestradiol-17beta; 3,17beta-Dihydroxy-2-methoxy-1,3,5(10)-estratriene

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 66414
  ChEBI ID: CHEBI:28955
  CAS Number: CAS 362-07-2
  TTD Drug ID: DMGBPME
  VARIDT Drug ID: DR00933
  INTEDE Drug ID: DR1863

Molecule-Related Drug Atlas

Drug(s) Targeting Hypoxia-inducible factor 1 alpha (HIF-1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HIF-1alpha	DM4OQRD	Lymphoma	2A80-2A86	Phase 4	[4]
IT-101	DMNDGWE	Solid tumour/cancer	2A00-2F9Z	Phase 3	[5]
PX-478	DM4AU8K	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
EZN-2968	DM2NBC7	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
ENMD-1198	DM9BJ3G	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
Pyrrolidine carboxamide derivative 1	DMJK98Z	N. A.	N. A.	Patented	[9]

Drug(s) Metabolized By Cytochrome P450 1A1 (CYP1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[10]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[11]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[12]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[13]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[14]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[15]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[16]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[17]
Riboflavin	DM8YMWE	Acne vulgaris	ED80	Approved	[18]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Hypoxia-inducible factor 1 alpha (HIF-1A)	TTQHWNA	HIF1A_HUMAN	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A1 (CYP1A1) Main DME	DE6OQ3W	CP1A1_HUMAN	Substrate	[3]

References

• [1] HIF-1-alpha and survivin involved in the anti-apoptotic effect of 2ME2 after global ischemia in rats. Neurol Res. 2011 Jul;33(6):583-92.
• [2] 2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squam... Clin Cancer Res. 2004 Dec 15;10(24):8665-73.
• [3] Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease. Mini Rev Med Chem. 2015;15(5):427-38.
• [4] A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther. 2008 Nov;7(11):3598-608.
• [5] CRLX101, an investigational camptothecin-containing nanoparticle-drug conjugate, targets cancer stem cells and impedes resistance to antiangiogenic therapy in mouse models of breast cancer. Breast Cancer Res Treat. 2015 Apr;150(3):559-67.
• [6] The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol Cancer Ther. 2009 Apr;8(4):947-58.
• [7] Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1), in patients with refractory solid tumors.Cancer Chemother Pharmacol.2014 Feb;73(2):343-8.
• [8] ENMD-1198, a new analogue of 2-methoxyestradiol, displays both antiangiogenic and vascular-disrupting properties. Mol Cancer Ther. 2010 May;9(5):1408-18.
• [9] Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2011-2015).Expert Opin Ther Pat. 2016;26(3):309-22.
• [10] Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics. 2000 Aug;10(6):519-30.
• [11] Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74.
• [12] Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94.
• [13] Preferred orientations in the binding of 4'-hydroxyacetanilide (acetaminophen) to cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation studies. J Med Chem. 1994 Mar 18;37(6):860-7.
• [14] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [15] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [16] A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med. 2005;43(7):702-6.
• [17] Cytochromes P450 in crustacea. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Nov;121(1-3):157-72.
• [18] Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone. Biochem J. 1998 Apr 1;331 ( Pt 1):273-81.
• [19] Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab. 2007 Aug;8(6):554-62.