Details of Disease

General Information of Disease (ID: DISWTJQL)

• Disease Name: Diarrhea
• Synonyms: diarrhoea of presumed infectious origin; diarrhea of presumed infectious origin; loose stools; frequent stools; diarrhoea; diarrheal disorder; diarrheal disease; diarrhea
• Disease Class: ME05: Bowel habit change
• Definition: The condition of having at least three loose or liquid bowel movements each day.
• Disease Hierarchy:
  DISWD40R: Disease
  DIS7JDYJ: Gastrointestinal disease
  DISWTJQL: Diarrhea
• ICD Code:
  ICD-11: ICD-11: ME05.1
  ICD-9: ICD-9: 787.91
  Expand ICD-11: 'ME05.1
  Expand ICD-9: 787.91
• Disease Identifiers:
  MONDO ID: MONDO_0001673
  MESH ID: D003967
  UMLS CUI: C1290807
  MedGen ID: 713159
  HPO ID: HP:0002014
  SNOMED CT ID: 128333008

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 17 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Attapulgite	DMDZFLK	Approved	Small molecular drug	[1]
Bismuth	DMTKU46	Approved	Small molecular drug	[2]
Cholestyramine	DM3370M	Approved	NA	[1]
Co-trimoxazole	DM2KF6N	Approved	NA	[1]
Diphenoxylate	DMO5SZX	Approved	Small molecular drug	[3]
Furazolidone	DM3P6V7	Approved	Small molecular drug	[4]
Irinotecan	DMP6SC2	Approved	Small molecular drug	[5]
Lactobacillus	DMT2CDZ	Approved	NA	[1]
Lamivudine	DMI347A	Approved	Small molecular drug	[6]
Loperamide	DMOJZQ9	Approved	Small molecular drug	[1]
Morphine	DMRMS0L	Approved	Small molecular drug	[7]
Nitazoxanide	DMOWLVG	Approved	Small molecular drug	[8]
Racecadotril	DMFOTZ7	Approved	Small molecular drug	[1]
Rifamycin	DMEH3O7	Approved	Small molecular drug	[9]
Saccharomyces boulardii	DM4VTZJ	Approved	NA	[1]
VRX496	DMIO4V5	Approved	Antisense drug	[10]
Zidovudine	DM4KI7O	Approved	Small molecular drug	[11]

This Disease is Treated as An Indication in 11 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
GT160-246	DM9IRCN	Phase 3	NA	[12]
MDX-066	DMTRUHW	Phase 3	NA	[13]
Recombinant factor VIII-Fc	DM1QQW6	Phase 3	NA	[14]
ACE-393	DMASEYX	Phase 2	NA	[15]
CR-3294	DMHJEZS	Phase 2	NA	[16]
Elsiglutide	DMB7CPG	Phase 2	NA	[17]
iOWH032	DM5TMYC	Phase 2	NA	[18]
RDP58	DM4CIKA	Phase 2	Small molecular drug	[19]
Shigella conjugated and outer membrane vaccine	DM7B2MN	Phase 2	NA	[20]
TIM ETEC vaccine	DMQ6UVX	Phase 2	NA	[21]
Peru-15 pCTB	DM4HC3O	Phase 1	NA	[22]

This Disease is Treated as An Indication in 7 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Needle-free ETEC vaccine	DMCV07F	Discontinued in Phase 3	NA	[23]
Sporidin-G	DM6AT99	Discontinued in Phase 3	NA	[24]
SYNSORB-Cd	DMSS42I	Discontinued in Phase 3	NA	[25]
DiffGAM	DM9JVMW	Discontinued in Phase 2	NA	[26]
LAGATIDE	DMC89R2	Discontinued in Phase 2	Small molecular drug	[27]
E coli vaccine	DMDPLIA	Discontinued in Phase 1	NA	[28]
LXR-0151	DMK1BXH	Discontinued in Phase 1	NA	[29]

This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
INP-1750	DMRNK8J	Investigative	NA	[30]
TZP-201	DMD6CLG	Investigative	NA	[31]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DGAT1	TT0GV3R	Strong	Genetic Variation	[32]
GUCY2C	TTLDPRG	Strong	Genetic Variation	[33]
PRKG2	TTDWFCQ	Strong	Biomarker	[34]
SLC9A3	TTFZVPO	Strong	Biomarker	[35]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP8B1	OTALGS63	Limited	Biomarker	[36]
TAPBP	OTL81AVZ	Limited	Altered Expression	[37]
PRSS57	OTR6GDQM	Strong	Genetic Variation	[38]
SH2D3A	OTVJBSRC	Strong	Biomarker	[39]
STX3	OT4CIWLJ	Strong	Genetic Variation	[40]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] The effect of histamine H2-receptor blockade on bismuth absorption from three ulcer-healing compounds. Gastroenterology. 1991 Oct;101(4):889-94.
• [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: 7164).
• [4] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 011270.
• [5] Irinotecan FDA Label
• [6] Lamivudine FDA Label
• [7] Morphine FDA Label
• [8] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 021497.
• [9] Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations.Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4832-E4840.
• [10] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [11] Zidovudine FDA Label
• [12] ClinicalTrials.gov (NCT00196794) A Study of GT267-004 Versus Vancomycin and GT267-004 Versus Metronidazole in Patients With C. Difficile-Associated Diarrhea. U.S. National Institutes of Health.
• [13] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021536)
• [14] Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014 Jan 16;123(3):317-25.
• [15] ClinicalTrials.gov (NCT00859716) ACE393-103 Vaccination Challenge Study. U.S. National Institutes of Health.
• [16] Efficacy of CR3294, a new benzamidine derivative, in the prevention of 5-fluorouracil-induced gastrointestinal mucositis and diarrhea in mice. Cancer Chemother Pharmacol. 2010 Oct;66(5):819-27.
• [17] ClinicalTrials.gov (NCT01543451) Proof-of-Concept Study in Cancer Patients to Assess Efficacy of Elsiglutide in Preventing Chemotherapy-Induced Diarrhea. U.S. National Institutes of Health.
• [18] ClinicalTrials.gov (NCT02111304) Efficacy of iOWH032 in Dehydrating Cholera. U.S. National Institutes of Health.
• [19] RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis. Inflamm Res. 2002 Nov;51(11):522-31.
• [20] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [21] New Medical Therapies of CenterWatch for treating Chronic Diarrhea, 2015.
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• [23] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024196)
• [24] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008789)
• [25] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008476)
• [26] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008511)
• [27] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005322)
• [28] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017674)
• [29] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006995)
• [30] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [31] 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: 297).
• [32] DGAT1 mutation is linked to a congenital diarrheal disorder. J Clin Invest. 2012 Dec;122(12):4680-4. doi: 10.1172/JCI64873. Epub 2012 Nov 1.
• [33] Guanylate cyclase C deficiency causes severe inflammation in a murine model of spontaneous colitis.PLoS One. 2013 Nov 11;8(11):e79180. doi: 10.1371/journal.pone.0079180. eCollection 2013.
• [34] Selective inhibition of intestinal guanosine 3',5'-cyclic monophosphate signaling by small-molecule protein kinase inhibitors.J Biol Chem. 2018 May 25;293(21):8173-8181. doi: 10.1074/jbc.RA118.002835. Epub 2018 Apr 13.
• [35] A common NHE3 single-nucleotide polymorphism has normal function and sensitivity to regulatory ligands. Am J Physiol Gastrointest Liver Physiol. 2017 Aug 1;313(2):G129-G137.
• [36] Analysis of 19 Highly Conserved Vibrio cholerae Bacteriophages Isolated from Environmental and Patient Sources Over a Twelve-Year Period.Viruses. 2018 Jun 1;10(6):299. doi: 10.3390/v10060299.
• [37] Antidiarrheal activity of -terpineol in mice.Biomed Pharmacother. 2019 Feb;110:631-640. doi: 10.1016/j.biopha.2018.11.131. Epub 2018 Dec 9.
• [38] G3P2 rotaviruses causing diarrhoeal disease in neonates differ in VP4, VP7 and NSP4 sequence from G3P2 strains causing asymptomatic neonatal infection.Arch Virol. 1996;141(9):1661-76. doi: 10.1007/BF01718290.
• [39] Rotavirus Species B Encodes a Functional Fusion-Associated Small Transmembrane Protein.J Virol. 2019 Sep 30;93(20):e00813-19. doi: 10.1128/JVI.00813-19. Print 2019 Oct 15.
• [40] MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update.Hum Mutat. 2018 Mar;39(3):333-344. doi: 10.1002/humu.23386. Epub 2018 Jan 17.