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

General Information of Drug (ID: DMUSJ96)

• Drug Name: Geldanamycin-estradiol hybrid Drug Info

Indication

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

• Cross-matching ID: TTD Drug ID: DMUSJ96

Molecule-Related Drug Atlas

Drug(s) Targeting Heat shock protein 90 alpha (HSP90A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cromoglicate	DM74LZK	Asthma	CA23	Approved	[2]
Amlexanox	DM0DQM5	Respiratory tract inflammation	CA07	Approved	[2]
NVP-AUY922	DMTYXQF	Multiple myeloma	2A83	Phase 2	[3]
BIIB-021	DMPAJ41	Breast cancer	2C60-2C65	Phase 2	[4]
KW-2478	DMJGL72	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
VER 50589	DMFLZPC	Breast cancer	2C60-2C65	Phase 2	[3]
Tanespimycin	DMNLQHK	Breast cancer	2C60-2C65	Phase 2	[6]
Efungumab	DMBHP56	Breast cancer	2C60-2C65	Phase 2	[7]
SNX-5422	DMIU0VP	Haematological malignancy	2B33.Y	Phase 1/2	[8]
PU3	DMJO0BP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

Drug(s) Targeting Estrogen receptor beta (ESR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conjugated estrogens	DMLT0E1	Menopause symptom	GA30.0	Approved	[9]
Trilostane	DMQZ9GF	Cushing disease	5A70	Approved	[10]
ARZOXIFENE	DMOKCVI	Breast cancer	2C60-2C65	Approved	[11]
Estrogen	DMGY0UT	Menopause symptom	GA30.0	Approved	[12]
Premarin/Pravachol	DMLSOB7	Hyperlipidaemia	5C80	Phase 3	[13]
MF-101	DM8Z0I3	Hepatitis virus infection	1E50-1E51	Phase 3	[14]
Genistein	DM0JETC	Menopause symptom	GA30.0	Phase 2/3	[15]
AUS-131	DMZMSQJ	Hot flushes	GA30	Phase 2	[16]
ERB-041	DMCEPUA	Inflammatory bowel disease	DD72	Phase 2	[17]
Erteberel	DMU1XZD	Prostate hyperplasia	GA90	Phase 2	[18]

Drug(s) Targeting Estrogen receptor (ESR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[19]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[20]
Estrone	DM5T6US	Menopausal and postmenopausal disorder	GA30	Approved	[20]
Estradiol valerate	DM8MC6O	Hormone replacement therapy	8E01	Approved	[10]
Estradiol acetate	DM07U2A	Hormone replacement therapy	8E01	Approved	[10]
Estradiol cypionate	DM27Z5T	Hormone replacement therapy	8E01	Approved	[10]
Ethinyl estradiol	DMODJ40	Female hypogonadism	GA30.6	Approved	[21]
Raloxifene	DMDKF3M	Osteoporosis	FB83.0	Approved	[22]
Ospemifene	DMC4GEI	Dyspareunia	GA12	Approved	[23]
Toremifene	DMQYUWG	Breast cancer	2C60-2C65	Approved	[24]

Drug(s) Targeting ERBB2 messenger RNA (HER2 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HKI-272	DM6QOVN	Breast cancer	2C60-2C65	Phase 3	[25]
BMS-690514	DMX302C	Chronic pain	MG30	Phase 2	[26]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[27]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[27]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[27]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[28]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[27]
PMID24915291C38	DMBXT9J	Discovery agent	N.A.	Investigative	[29]
CL-387785	DMLKFZC	Discovery agent	N.A.	Investigative	[30]
HDS-029	DMLRUVA	Discovery agent	N.A.	Investigative	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
ERBB2 messenger RNA (HER2 mRNA)	TTR5TV4	ERBB2_HUMAN	Inhibitor	[1]
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Inhibitor	[1]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[1]
Heat shock protein 90 alpha (HSP90A)	TT78R5H	HS90A_HUMAN	Inhibitor	[1]

References

• [1] Synthesis and evaluation of geldanamycin-estradiol hybrids. Bioorg Med Chem Lett. 1999 May 3;9(9):1233-8.
• [2] Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and amlexanox. Biochem J. 2003 Sep 1;374(Pt 2):433-41.
• [3] Recent advances in Hsp90 inhibitors as antitumor agents. Anticancer Agents Med Chem. 2008 Oct;8(7):761-82.
• [4] BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Mol Cancer Ther. 2009 Apr;8(4):921-9.
• [5] Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib. Blood Cancer J. 2012 Apr;2(4):e68.
• [6] Tanespimycin: the opportunities and challenges of targeting heat shock protein 90. Expert Opin Investig Drugs. 2009 Jun;18(6):861-8.
• [7] Efungumab: a novel agent in the treatment of invasive candidiasis. Ann Pharmacother. 2009 Nov;43(11):1818-23.
• [8] SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hema... Blood. 2009 Jan 22;113(4):846-55.
• [9] Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. J Med Chem. 2007 May 31;50(11):2682-92.
• [12] 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.
• [13] Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov. 2003 Jul;2(7):517-26.
• [14] 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.
• [15] Company report (Axcentua)
• [16] 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.
• [17] 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.
• [18] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031986)
• [19] 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.
• [20] Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
• [21] 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
• [22] 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).
• [23] Clinical pipeline report, company report or official report of Shionogi (2011).
• [24] 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.
• [25] Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19936-41.
• [26] Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.
• [27] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [28] Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
• [29] Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28.
• [30] Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB... J Med Chem. 2006 Feb 23;49(4):1475-85.