General Information of Drug Combination (ID: DCBLT01)

Drug Combination Name
Levonorgestrel Semaglutide
Indication
Disease Entry Status REF
Endometrial Cancer Phase 2 [1]
Component Drugs Levonorgestrel   DM1DP7T Semaglutide   DMAGFOD
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Levonorgestrel
Disease Entry ICD 11 Status REF
Atypical endometrial hyperplasia N.A. Approved [2]
Contraception QA21 Approved [3]
Hot flushes GA30 Approved [2]
Menorrhagia GA20.50 Approved [2]
Levonorgestrel Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Progesterone receptor (PGR) TTUV8G9 PRGR_HUMAN Binder [6]
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Levonorgestrel Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [7]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Decreases Activity [8]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) OTQ4W7MT TR11B_HUMAN Increases Expression [9]
Tumor necrosis factor ligand superfamily member 11 (TNFSF11) OTJEPKEQ TNF11_HUMAN Decreases Expression [9]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Affects Expression [10]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Decreases Secretion [11]
Sex hormone-binding globulin (SHBG) OTPWU5IW SHBG_HUMAN Affects Binding [12]
Prostate-specific antigen (KLK3) OTFGSBFJ KLK3_HUMAN Increases Expression [13]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [14]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [14]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of Semaglutide
Disease Entry ICD 11 Status REF
Type-2 diabetes 5A11 Approved [4]
Semaglutide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Glucagon-like peptide 1 receptor (GLP1R) TTVIMDE GLP1R_HUMAN Agonist [15]
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Semaglutide Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Dipeptidyl peptidase IV (DPP4) DEKZQY6 DPP4_HUMAN Metabolism [16]
Neprilysin (MME) DEVN830 NEP_HUMAN Metabolism [16]
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References

1 ClinicalTrials.gov (NCT06073184) Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium
2 Levonorgestrel FDA Label
3 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: 2881).
4 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
5 Effects of 17beta-estradiol, progesterone, synthetic progestins, tibolone, and raloxifene on vascular endothelial growth factor and Thrombospondin-1 messenger RNA in breast cancer cells. Int J Gynecol Cancer. 2006;16 Suppl 2:560-3. doi: 10.1111/j.1525-1438.2006.00696.x.
6 Met909 plays a key role in the activation of the progesterone receptor and also in the high potency of 13-ethyl progestins. Mol Pharmacol. 2009 Jun;75(6):1317-24.
7 P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res. 2004 Jul;21(7):1284-93.
8 Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and AKR1C3. Chem Biol Interact. 2011 May 30;191(1-3):227-33.
9 [Effect of nylestriol and levonorgestrel on the expression of Opg/OPGL in human osteosarcoma MG-63 cell lines]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004 Dec;29(6):667-70.
10 Study of low-density lipoprotein receptor regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-3 cell line and placental tissue. Contraception. 2007 Oct;76(4):297-305. doi: 10.1016/j.contraception.2007.06.011. Epub 2007 Sep 14.
11 Relative progestational and androgenic activity of four progestins used for male hormonal contraception assessed in vitro in relation to their ability to suppress LH secretion in the castrate male rat. Mol Cell Endocrinol. 2010 Oct 26;328(1-2):16-21. doi: 10.1016/j.mce.2010.06.010. Epub 2010 Jun 25.
12 Serum distribution of the major metabolites of norgestimate in relation to its pharmacological properties. Contraception. 2003 Feb;67(2):93-9. doi: 10.1016/s0010-7824(02)00473-0.
13 Effects of natural products and nutraceuticals on steroid hormone-regulated gene expression. Clin Chim Acta. 2001 Oct;312(1-2):213-9. doi: 10.1016/s0009-8981(01)00626-x.
14 Effect of menstrual cycle and hormonal treatment on ki-67 and bcl-2 expression and adenomyosis. Gynecol Endocrinol. 2005 Mar;20(3):127-31. doi: 10.1080/09513590400021086.
15 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: 249).
16 Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017 Jun 15;104:31-41.