Details of the Drug Combination

General Information of Drug Combination (ID: DCRUE77)

• Drug Combination Name: 2,3-dihydroxypropanal + Empagliflozin
• Indication: Obesity, Visceral; Status: Phase 4 [1]
• Component Drugs:
  2,3-dihydroxypropanal (DMOWNB4): Small molecular drug
  Empagliflozin (DMRF9YK): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of 2,3-dihydroxypropanal

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

2,3-dihydroxypropanal Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aldose reductase (AKR1B1)	TTFBNVI	ALDR_HUMAN	Inhibitor	[2]

2,3-dihydroxypropanal Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Aldo-keto reductase 1A1 (AKR1A1)	DED2FW3	AK1A1_HUMAN	Metabolism	[4]

2,3-dihydroxypropanal Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Increases Metabolism	[5]
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Increases Reduction	[6]
Short-chain dehydrogenase/reductase 3 (DHRS3)	OTSK1DTP	DHRS3_HUMAN	Increases Metabolism	[7]
Aldo-keto reductase family 1 member B15 (AKR1B15)	OTUEXSWH	AK1BF_HUMAN	Increases Metabolism	[8]

Indication(s) of Empagliflozin

Disease Entry	ICD 11	Status	REF
Type-1 diabetes	5A10	Approved	[3]

Empagliflozin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium/glucose cotransporter 2 (SGLT2)	TTLWPVF	SC5A2_HUMAN	Modulator	[9]

Empagliflozin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[11]

Empagliflozin Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A8 (UGT1A8)	DE2GB8N	UD18_HUMAN	Metabolism	[12]

References

• [1] ClinicalTrials.gov (NCT02833415) Visceral Adiposity and Diabetes: Translating Form to Function Using Imaging
• [2] Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20764-9.
• [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: 4754).
• [4] The C-terminal loop of aldehyde reductase determines the substrate and inhibitor specificity. Biochemistry. 1996 Nov 12;35(45):14276-80.
• [5] Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers. Eur J Pharmacol. 2008 Apr 28;584(2-3):213-21.
• [6] Aldo-keto reductases from the AKR1B subfamily: retinoid specificity and control of cellular retinoic acid levels. Chem Biol Interact. 2009 Mar 16;178(1-3):171-7. doi: 10.1016/j.cbi.2008.10.027. Epub 2008 Oct 25.
• [7] Molecular and biochemical characterisation of human short-chain dehydrogenase/reductase member 3 (DHRS3). Chem Biol Interact. 2015 Jun 5;234:178-87.
• [8] Functional expression of novel human and murine AKR1B genes. Chem Biol Interact. 2011 May 30;191(1-3):177-84.
• [9] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [10] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [11] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
• [12] Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.