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

General Information of Drug (ID: DMROWV8)

• Drug Name: ZK-164015 Drug Info
• Synonyms: ZK 164015; 177583-70-9; ZK-164015; 2-(4-HYDROXYPHENYL)-3-METHYL-1-[10-(PENTYLSULFONYL)DECYL]-1H-INDOL-5-OL; CHEMBL184074; SCHEMBL7133598; CHEBI:92087; CTK4D6535; DTXSID00430964; MolPort-006-822-606; HMS3268P09; ZINC8022535; AKOS024456974; NCGC00092322-01; RT-016336; B6960; J-011295; BRD-K05151076-001-01-8

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9806489
  ChEBI ID: CHEBI:92087
  CAS Number: CAS 177583-70-9
  TTD Drug ID: DMROWV8

Molecule-Related Drug Atlas

Drug(s) Targeting Estrogen receptor beta (ESR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conjugated Estrogens	DMLT0E1	Dyspareunia	GA12	Approved	[3]
Trilostane	DMQZ9GF	Cushing disease	5A70	Approved	[4]
ARZOXIFENE	DMOKCVI	Breast cancer	2C60-2C65	Approved	[5]
Estrogen	DMGY0UT	Menopause symptom	GA30.0	Approved	[6]
MF-101	DM8Z0I3	Hepatitis virus infection	1E50-1E51	Phase 3	[7]
Genistein	DM0JETC	Menopause symptom	GA30.0	Phase 2/3	[8]
AUS-131	DMUXO3Z	Hot flushes	GA30	Phase 2	[9]
ERB-041	DMCEPUA	Inflammatory bowel disease	DD72	Phase 2	[10]
Erteberel	DMU1XZD	Prostate hyperplasia	GA90	Phase 2	[11]
VG-101	DMAN21O	Menopause symptom	GA30.0	Phase 1/2	[12]

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[14]
Estradiol Valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[4]
Estradiol Acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[4]
Estradiol Cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[4]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[15]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[16]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[17]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[18]

Drug(s) Affected By Steryl-sulfatase (STS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[19]
Tazarotene	DM8SMD1	Acne vulgaris	ED80	Approved	[21]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[24]
Danazol	DML8KTN	Menorrhagia	GA20.50	Approved	[25]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[21]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Inhibitor	[1]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Steryl-sulfatase (STS)	OTXTJQPC	STS_HUMAN	Gene/Protein Processing	[2]

References

• [1] Synthesis and biological evaluation of stilbene-based pure estrogen antagonists. Bioorg Med Chem Lett. 2004 Sep 20;14(18):4659-63.
• [2] Sulfamoyloxy-substituted 2-phenylindoles: antiestrogen-based inhibitors of the steroid sulfatase in human breast cancer cells. Bioorg Med Chem. 2002 Dec;10(12):3941-53. doi: 10.1016/s0968-0896(02)00306-1.
• [3] Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. J Med Chem. 2007 May 31;50(11):2682-92.
• [6] Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient female mice. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15133-6.
• [7] MF101, a selective estrogen receptor beta modulator for the treatment of menopausal hot flushes: a phase II clinical trial. Menopause. 2009 May-Jun;16(3):458-65.
• [8] Company report (Axcentua)
• [9] S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr. 2005 May;81(5):1072-9.
• [10] Erb-041, an estrogen receptor-beta agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway. Cancer Prev Res (Phila). 2014 Feb;7(2):186-98.
• [11] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031986)
• [12] Update on alternative therapies for vulvovaginal atrophy. Patient Prefer Adherence. 2011; 5: 533-536.
• [13] Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
• [14] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [15] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [16] 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. (Target id: 620).
• [17] Clinical pipeline report, company report or official report of Shionogi (2011).
• [18] Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithe... Prostate Cancer Prostatic Dis. 2009;12(4):375-81.
• [19] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [20] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [21] Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways. J Cell Biochem. 2006 Feb 1;97(2):327-50. doi: 10.1002/jcb.20579.
• [22] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [23] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] Synthesis and steroid sulphatase inhibitory activity of C19- and C21-steroidal derivatives bearing a benzyl-inhibiting group. Eur J Med Chem. 2001 Jul-Aug;36(7-8):659-71. doi: 10.1016/s0223-5234(01)01262-4.