Details of the Drug

General Information of Drug (ID: DMLT0E1)

• Drug Name: Conjugated Estrogens
• Synonyms: Par Estro; evex; Premarin; Conestoral; NSC18313; Sodium estrone 3-monosulfate; Estrone, hydrogen sulfate sodium salt; AC1NS0NL; NSC-18313; sodium [(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate; Estra-1,5(10)-trien-17-one, 3-(sulfooxy)-, sodium; Carentil; Congest; Estroplus; Evex; Menotabs; Oestrogen; Prelestrin; Presomil; Progens; Conjugated Equine Estrogens; Conjugated Estrogenic Substances; Conjugated estrogenic hormones; Conjugated oestrogens; Conjugated oestrogens [Steroidal oestrogens]; Steroidal estrogens; ASTA Medica Brand of Estrogens, Conjugated; Almirall Brand of Estrogens, Conjugated; Equine Estrogens, Conjugated; Estro-Feminal; Estrogenic Hormones, Conjugated; Estrogenic substances, conjugated; Estrogens, conjugated USP; Estrogens, conjugated [USP]; Estrogens, conjugated synthetic A; Estrogens, steroidal; Solvay Brand of Estrogens, Conjugated; Trianon Brand of Estrogens, Conjugated; Wyeth Brand of Estrogens, Conjugated; Estrogens, conjugated (USP); Estrogens, conjugated-equine; Mack Brand of Estrogens, Conjugated (USP); Major Brand of Estrogens, Conjugated (USP); Pasadena Brand of Estrogens, Conjugated (USP); Pharmacia Brand of Estrogens, Conjugated (USP); CES; Estra-1,3,5(10)-trien-17-one, 3-(sulfooxy)-, sodium salt; Sodium [(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate

Indication

Disease Entry	ICD 11	Status	REF
Dyspareunia	GA12	Approved	[1]
Hot flushes	GA30	Approved	[2]
Menopause symptom	GA30.0	Approved	[3]
Vasomotor symptom	CA08	Approved	[4]

• Therapeutic Class: Estrogens
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 372.4
  Logarithm of the Partition Coefficient; Not Available
  Rotatable Bond Count; 2
  Hydrogen Bond Donor Count; 0
  Hydrogen Bond Acceptor Count; 5
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 35 mcgh/L [5]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 2.6 mcg/L [5]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 7 h [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 17 hours [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.09169 micromolar/kg/day [6]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Bone density increased	Not Available	ESR1	OTKLU61J	[7]

• Chemical Identifiers:
  Formula: C18H21NaO5S
  IUPAC Name: sodium;[(13S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfate
  Canonical SMILES: C[C@]12CCC3C(C1CCC2=O)CCC4=C3C=CC(=C4)OS(=O)(=O)[O-].[Na+]
  InChI: InChI=1S/C18H22O5S.Na/c1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19;/h3,5,10,14-16H,2,4,6-9H2,1H3,(H,20,21,22);/q;+1/p-1/t14?,15?,16?,18-;/m0./s1
  InChIKey: VUCAHVBMSFIGAI-TWCWWGPMSA-M
• Cross-matching ID:
  PubChem CID: 45357473
  DrugBank ID: DB00286
  TTD ID: D0T0LU
  VARIDT ID: DR00673
  INTEDE ID: DR0377
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

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

Drug-Metabolizing Enzyme (DME)

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

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Drug Response	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Dyspareunia
• ICD Disease Classification: GA12

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Estrogen receptor beta (ESR2)	DTT	ESR2	2.09E-01	-0.06	-0.17
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	4.89E-02	-3.74E-01	-6.96E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.10E-01	-1.23E-01	-2.88E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Conjugated Estrogens (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Conjugated estrogens caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[12]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Conjugated estrogens caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[12]
Mitotane	DMU1GX0	Moderate	Increased metabolism of Conjugated estrogens caused by Mitotane mediated induction of CYP450 enzyme.	Adrenal cancer [2D11]	[12]
Dronedarone	DMA8FS5	Moderate	Decreased clearance of Conjugated estrogens due to the transporter inhibition by Dronedarone.	Angina pectoris [BA40]	[13]
Methylphenobarbital	DMDSWAG	Moderate	Increased metabolism of Conjugated estrogens caused by Methylphenobarbital mediated induction of CYP450 enzyme.	Anxiety disorder [6B00-6B0Z]	[14]
Voriconazole	DMAOL2S	Moderate	Decreased metabolism of Conjugated estrogens caused by Voriconazole mediated inhibition of CYP450 enzyme.	Aspergillosis [1F20]	[15]
Posaconazole	DMUL5EW	Moderate	Decreased metabolism of Conjugated estrogens caused by Posaconazole mediated inhibition of CYP450 enzyme.	Aspergillosis [1F20]	[15]
Clarithromycin	DM4M1SG	Moderate	Decreased metabolism of Conjugated estrogens caused by Clarithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[16]
Telithromycin	DMZ4P3A	Moderate	Decreased metabolism of Conjugated estrogens caused by Telithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[17]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Conjugated estrogens caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[12]
Lapatinib	DM3BH1Y	Moderate	Decreased clearance of Conjugated estrogens due to the transporter inhibition by Lapatinib.	Breast cancer [2C60-2C6Y]	[18]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Conjugated estrogens caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[19]
Atorvastatin	DMF28YC	Minor	Decreased metabolism of Conjugated estrogens caused by Atorvastatin mediated inhibition of CYP450 enzyme.	Cardiovascular disease [BA00-BE2Z]	[20]
Secobarbital	DM14RF5	Moderate	Increased metabolism of Conjugated estrogens caused by Secobarbital mediated induction of CYP450 enzyme.	Chronic insomnia [7A00]	[12]
Phenylbutazone	DMAYL0T	Moderate	Increased metabolism of Conjugated estrogens caused by Phenylbutazone mediated induction of CYP450 enzyme.	Chronic pain [MG30]	[12]
Anisindione	DM2C48U	Moderate	Antagonize the effect of Conjugated estrogens when combined with Anisindione.	Coagulation defect [3B10]	[21]
Mifepristone	DMGZQEF	Moderate	Decreased metabolism of Conjugated estrogens caused by Mifepristone mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[16]
Aminoglutethimide	DMWFHMZ	Moderate	Increased metabolism of Conjugated estrogens caused by Aminoglutethimide mediated induction of CYP450 enzyme.	Cushing syndrome [5A70]	[12]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Conjugated estrogens caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[22]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Conjugated estrogens caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[16]
Aprepitant	DM053KT	Moderate	Decreased metabolism of Conjugated estrogens caused by Aprepitant mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[23]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Conjugated estrogens caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[24]
Griseofulvin	DMK54YG	Moderate	Increased metabolism of Conjugated estrogens caused by Griseofulvin mediated induction of CYP450 enzyme.	Dermatophytosis [1F28]	[12]
Primidone	DM0WX6I	Moderate	Increased metabolism of Conjugated estrogens caused by Primidone mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Oxcarbazepine	DM5PU6O	Moderate	Increased metabolism of Conjugated estrogens caused by Oxcarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Cenobamate	DM8KLU9	Moderate	Increased metabolism of Conjugated estrogens caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Fosphenytoin	DMOX3LB	Moderate	Increased metabolism of Conjugated estrogens caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Conjugated estrogens caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[25]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Conjugated estrogens caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Carbamazepine	DMZOLBI	Moderate	Increased metabolism of Conjugated estrogens caused by Carbamazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Conjugated estrogens caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Dantrolene	DM1D8XY	Major	Increased risk of hepatotoxicity by the combination of Conjugated estrogens and Dantrolene.	Fever [MG26]	[26]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Conjugated estrogens caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[27]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Conjugated estrogens caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[15]
Miconazole	DMPMYE8	Moderate	Decreased metabolism of Conjugated estrogens caused by Miconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[15]
Ketoconazole	DMPZI3Q	Moderate	Decreased metabolism of Conjugated estrogens caused by Ketoconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[15]
Cimetidine	DMH61ZB	Minor	Decreased metabolism of Conjugated estrogens caused by Cimetidine.	Gastro-oesophageal reflux disease [DA22]	[28]
Sulfinpyrazone	DMEV954	Moderate	Increased metabolism of Conjugated estrogens caused by Sulfinpyrazone mediated induction of CYP450 enzyme.	Gout [FA25]	[12]
Boceprevir	DMBSHMF	Moderate	Decreased metabolism of Conjugated estrogens caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[29]
ABT-450	DMFW860	Major	Decreased metabolism of Conjugated estrogens caused by ABT-450 mediated inhibition of UGT.	Hepatitis virus infection [1E50-1E51]	[30]
Telaprevir	DMMRV29	Moderate	Decreased metabolism of Conjugated estrogens caused by Telaprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[31]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Conjugated estrogens caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[14]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Conjugated estrogens caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[12]
Delavirdine	DM3NF5G	Minor	Decreased metabolism of Conjugated estrogens caused by Delavirdine mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[32]
Tipranavir	DM8HJX6	Moderate	Increased risk of skin rash by the combination of Conjugated estrogens and Tipranavir.	Human immunodeficiency virus disease [1C60-1C62]	[33]
Efavirenz	DMC0GSJ	Moderate	Increased metabolism of Conjugated estrogens caused by Efavirenz mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Saquinavir	DMG814N	Moderate	Decreased metabolism of Conjugated estrogens caused by Saquinavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[34]
Darunavir	DMN3GCH	Moderate	Decreased metabolism of Conjugated estrogens caused by Darunavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[35]
Ritonavir	DMU764S	Moderate	Decreased metabolism of Conjugated estrogens caused by Ritonavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Diltiazem	DMAI7ZV	Moderate	Decreased metabolism of Conjugated estrogens caused by Diltiazem mediated inhibition of CYP450 enzyme.	Hypertension [BA00-BA04]	[36]
Conivaptan	DM1V329	Moderate	Decreased metabolism of Conjugated estrogens caused by Conivaptan mediated inhibition of CYP450 enzyme.	Hypo-osmolality/hyponatraemia [5C72]	[37]
Levothyroxine	DMHN027	Moderate	Decreased plasma concentration of Conjugated estrogens caused by Levothyroxine mediated increased concentration of serum thyroid-binding globulin.	Hypo-thyroidism [5A00]	[38]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Conjugated estrogens caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[39]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Conjugated estrogens caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[12]
Pentobarbital	DMFNH7L	Moderate	Increased metabolism of Conjugated estrogens caused by Pentobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[12]
Melatonin	DMKWFBT	Minor	Decreased metabolism of Conjugated estrogens caused by Melatonin mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[16]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Conjugated estrogens caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[40]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Conjugated estrogens caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[12]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Conjugated estrogens caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[25]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Conjugated estrogens caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[41]
Vemurafenib	DM62UG5	Moderate	Increased metabolism of Conjugated estrogens caused by Vemurafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[12]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Conjugated estrogens caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[12]
Exjade	DMHPRWG	Moderate	Decreased metabolism of Conjugated estrogens caused by Exjade mediated inhibition of CYP450 enzyme.	Mineral absorption/transport disorder [5C64]	[42]
Carfilzomib	DM48K0X	Major	Additive thrombogenic effects by the combination of Conjugated estrogens and Carfilzomib.	Multiple myeloma [2A83]	[16]
Rifabutin	DM1YBHK	Moderate	Increased metabolism of Conjugated estrogens caused by Rifabutin mediated induction of CYP450 enzyme.	Mycobacterium infection [1B10-1B21]	[12]
Bexarotene	DMOBIKY	Moderate	Increased metabolism of Conjugated estrogens caused by Bexarotene mediated induction of CYP450 enzyme.	Mycosis fungoides [2B01]	[12]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Conjugated estrogens caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[25]
Nilotinib	DM7HXWT	Moderate	Decreased clearance of Conjugated estrogens due to the transporter inhibition by Nilotinib.	Myeloproliferative neoplasm [2A20]	[43]
Imatinib	DM7RJXL	Moderate	Decreased metabolism of Conjugated estrogens caused by Imatinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[44]
Dasatinib	DMJV2EK	Moderate	Decreased metabolism of Conjugated estrogens caused by Dasatinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[45]
Modafinil	DMYILBE	Minor	Increased metabolism of Conjugated estrogens caused by Modafinil mediated induction of CYP450 enzyme.	Narcolepsy [7A20]	[46]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Conjugated estrogens caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[47]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Conjugated estrogens caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[48]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Conjugated estrogens caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[49]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Conjugated estrogens caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[12]
Bosentan	DMIOGBU	Moderate	Increased metabolism of Conjugated estrogens caused by Bosentan mediated induction of CYP450 enzyme.	Pulmonary hypertension [BB01]	[12]
Nafcillin	DMN9RPO	Moderate	Increased metabolism of Conjugated estrogens caused by Nafcillin mediated induction of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[12]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Conjugated estrogens caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[50]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Conjugated estrogens caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[25]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Conjugated estrogens caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[16]
Armodafinil	DMGB035	Minor	Increased metabolism of Conjugated estrogens caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[46]
Warfarin	DMJYCVW	Moderate	Antagonize the effect of Conjugated estrogens when combined with Warfarin.	Supraventricular tachyarrhythmia [BC81]	[21]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Conjugated estrogens caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[51]

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• [49] Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
• [50] Product Information. Oxbryta (voxelotor). Global Blood Therapeutics, Inc., South San Francisco, CA.
• [51] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.