Details of the Drug Combination

General Information of Drug Combination (ID: DCASCDK)

• Drug Combination Name: Chlorthalidone + Indapamide
• Indication: Kidney Stone; Status: Phase 2 [1]
• Component Drugs:
  Chlorthalidone (DM4DMBT): Small molecular drug
  Indapamide (DMGN1PW): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Chlorthalidone

Disease Entry	ICD 11	Status	REF
Edema	MG29	Approved	[2]
Hypertension	BA00-BA04	Approved	[2]
High blood pressure	BA00	Investigative	[3]

Chlorthalidone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Solute carrier family 12 member 1 (SLC12A1)	TTS087L	S12A1_HUMAN	Blocker	[6]

Chlorthalidone Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[7]

Indication(s) of Indapamide

Disease Entry	ICD 11	Status	REF
Edema	MG29	Approved	[4]
Hypertension	BA00-BA04	Approved	[5]
Malignant essential hypertension	BA00	Approved	[4]

Indapamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated potassium channel Kv7.1 (KCNQ1)	TT846HF	KCNQ1_HUMAN	Blocker	[8]

Indapamide Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]

Indapamide Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[10]
HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA)	OTZE5Q7R	DOA_HUMAN	Affects Expression	[11]
Alpha-2A adrenergic receptor (ADRA2A)	OTZFGOTP	ADA2A_HUMAN	Increases Expression	[12]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Affects Expression	[11]

References

• [1] ClinicalTrials.gov (NCT06111885) Indapamide and Chlorthalidone to Reduce Urine Supersaturation for Kidney Stone Prevention
• [2] 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: 7147).
• [3] Chlorthalidone FDA Label
• [4] Indapamide FDA Label
• [5] 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: 7203).
• [6] The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52.
• [7] Detection of low-renin hypertension; evaluation of out-patient renin-stimulating methods. Clin Sci Mol Med. 1975 Feb;48(2):91-6. doi: 10.1042/cs0480091.
• [8] Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents. Eur J Pharmacol. 2006 Apr 24;536(1-2):78-84.
• [9] Dehydrogenation of the indoline-containing drug 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (indapamide) by CYP3A4: correlation with in silico predictions. Drug Metab Dispos. 2009 Mar;37(3):672-84.
• [10] Antihypertensive effect of indapamide with special emphasis on renal prostaglandin production. Curr Med Res Opin. 1983;8 Suppl 3:81-6. doi: 10.1185/03007998309109841.
• [11] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [12] Platelet alpha 2-adrenoceptor modifications induced by long-term treatment with indapamide in essential hypertension. Am J Med. 1988 Jan 29;84(1B):31-5.