Details of the Drug Combination

General Information of Drug Combination (ID: DCCN5ZP)

• Drug Combination Name: Estriol + Norethindrone
• Indication: Relapsing-remitting Multiple Sclerosis; Status: Phase 1 [1]
• Component Drugs:
  Estriol (DMOEM2I): Small molecular drug
  Norethindrone (DMTY169): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Estriol

Disease Entry	ICD 11	Status	REF
Hormone deficiency	5A61.1	Approved	[2]
Multiple sclerosis	8A40	Phase 2	[3]

Estriol Interacts with 1 DTT Molecule(s)

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

Estriol Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]

Estriol Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[15]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[16]

Estriol Interacts with 32 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[14]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Expression	[17]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Expression	[18]
Sulfotransferase 1E1 (SULT1E1)	OTGPJ517	ST1E1_HUMAN	Decreases Activity	[19]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Expression	[20]
Coagulation factor X (F10)	OT2BLK17	FA10_HUMAN	Increases Expression	[21]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Decreases Expression	[22]
Alpha-fetoprotein (AFP)	OT9GG3ZI	FETA_HUMAN	Increases Expression	[23]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[24]
Platelet-derived growth factor subunit A (PDGFA)	OTCMZ0W8	PDGFA_HUMAN	Decreases Expression	[22]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Increases Expression	[25]
Sex hormone-binding globulin (SHBG)	OTPWU5IW	SHBG_HUMAN	Affects Binding	[26]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Increases Expression	[27]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[22]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Increases Expression	[24]
Gamma-enolase (ENO2)	OTRODL0T	ENOG_HUMAN	Decreases Expression	[8]
Beta-1,4-galactosyltransferase 1 (B4GALT1)	OTBCXEK7	B4GT1_HUMAN	Increases Expression	[28]
Insulin-like growth factor-binding protein 5 (IGFBP5)	OTRE5V0C	IBP5_HUMAN	Decreases Expression	[8]
Type-1 angiotensin II receptor (AGTR1)	OT2NRMJP	AGTR1_HUMAN	Decreases Expression	[8]
Hepatocyte nuclear factor 4-alpha (HNF4A)	OTY1TOAB	HNF4A_HUMAN	Decreases Expression	[29]
Rho GDP-dissociation inhibitor 1 (ARHGDIA)	OTEXWJDO	GDIR1_HUMAN	Decreases Expression	[8]
Solute carrier family 12 member 2 (SLC12A2)	OT3ZJ3LH	S12A2_HUMAN	Decreases Expression	[8]
Actin, alpha cardiac muscle 1 (ACTC1)	OTJU04B1	ACTC_HUMAN	Affects Expression	[29]
Early growth response protein 3 (EGR3)	OTGPJIRA	EGR3_HUMAN	Increases Expression	[8]
Methanethiol oxidase (SELENBP1)	OT3NZNTR	SBP1_HUMAN	Decreases Expression	[8]
Advanced glycosylation end product-specific receptor (AGER)	OTPY0IH7	RAGE_HUMAN	Increases Expression	[30]
Na(+)/H(+) exchange regulatory cofactor NHE-RF3 (PDZK1)	OTGFK4MH	NHRF3_HUMAN	Increases Expression	[28]
Early estrogen-induced gene 1 protein (EEIG1)	OT2BMEAE	EEIG1_HUMAN	Increases Expression	[28]
Estrogen receptor beta (ESR2)	OTXNR2WQ	ESR2_HUMAN	Affects Binding	[31]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[8]
Hepatocyte nuclear factor 3-beta (FOXA2)	OTJOCVOY	FOXA2_HUMAN	Increases Expression	[29]
T-box transcription factor TBX19 (TBX19)	OTXEMR2U	TBX19_HUMAN	Decreases Abundance	[32]

Indication(s) of Norethindrone

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[4]
Advanced cancer	2A00-2F9Z	Approved	[4]
Hot flushes	GA30	Approved	[4]
Menorrhagia	GA20.50	Approved	[4]
Obsolete atrophic vulva	N.A.	Approved	[4]
Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Endometriosis	GA10	Investigative	[4]

Norethindrone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Agonist	[34]

Norethindrone Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[14]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[35]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[36]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[36]
Serine/threonine-protein kinase Sgk1 (SGK1)	OT301T1U	SGK1_HUMAN	Increases Expression	[37]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Increases Secretion	[38]
Myb-related protein A (MYBL1)	OTBJMC2P	MYBA_HUMAN	Increases Expression	[37]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[39]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[40]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Increases Activity	[41]
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Increases Expression	[37]

References

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• [4] Norethindrone FDA Label
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