Details of the Drug Combination

General Information of Drug Combination (ID: DCLC4NQ)

• Drug Combination Name: Conjugated Estrogens + Bazedoxifene
• Indication: Postmenopausal osteoporosis; Status: Phase 1 [1]
• Component Drugs:
  Conjugated Estrogens (DMLT0E1): Small molecular drug
  Bazedoxifene (DMY85QW): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Conjugated Estrogens

Disease Entry	ICD 11	Status	REF
Dyspareunia	GA12	Approved	[2]
Hot flushes	GA30	Approved	[3]
Menopause symptom	GA30.0	Approved	[4]
Vasomotor symptom	CA08	Approved	[5]

Conjugated Estrogens Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Antagonist	[8]

Conjugated Estrogens Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[10]
Beta-glucuronidase (uidA)	DE9RA0I	BGLR_ECOLI	Metabolism	[11]

Conjugated Estrogens Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases ADR	[12]

Indication(s) of Bazedoxifene

Disease Entry	ICD 11	Status	REF
Hot flushes	GA30	Approved	[6]
Osteopetrosis	LD24.10	Approved	[7]

Bazedoxifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[13]

Bazedoxifene Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[14]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[15]
Beta-glucuronidase (uidA)	DEWTCUK	Q9AHJ8_LACGS	Metabolism	[11]

References

• [1] Breast effects of bazedoxifene-conjugated estrogens: a randomized controlled trial. Obstet Gynecol. 2013 May;121(5):959-68.
• [2] Drugs for menopausal symptoms. Med Lett Drugs Ther. 2020 Aug 10;62(1604):124-128.
• [3] Raloxifene. Drugs Aging. 1998 Apr;12(4):335-41; discussion 342.
• [4] ClinicalTrials.gov (NCT01613170) Premarin Versus Toviaz for Treatment of Overactive Bladder. U.S. National Institutes of Health.
• [5] Roles of hormone replacement therapy and iron in proliferation of breast epithelial cells with different estrogen and progesterone receptor status. Breast. 2008 Apr;17(2):172-9.
• [6] Bazedoxifene FDA Label
• [7] 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. (Ligand id: 7355).
• [8] Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
• [9] Conjugated oestrogens/bazedoxifene. Aust Prescr. 2017 Jun;40(3):114-115.
• [10] Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women. J Clin Pharmacol. 2006 Nov;46(11):1299-307.
• [11] Long-term administration of conjugated estrogen and bazedoxifene decreased murine fecal beta-glucuronidase activity without impacting overall microbiome community. Sci Rep. 2018 May 25;8(1):8166.
• [12] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [13] Bazedoxifene, a selective estrogen receptor modulator: effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women. Menopause. 2009 Nov-Dec;16(6):1109-15.
• [14] UGT1A1*28 polymorphism influences glucuronidation of bazedoxifene. Pharmazie. 2015 Feb;70(2):94-6.
• [15] In vitro metabolism, permeability, and efflux of bazedoxifene in humans. Drug Metab Dispos. 2010 Sep;38(9):1471-9.