Details of the Drug

General Information of Drug (ID: DMENSL5)

• Drug Name: Aminosalicylic Acid
• Synonyms: 4-Aminosalicylic acid; 65-49-6; Aminosalicylic acid; P-AMINOSALICYLIC ACID; Rezipas; Aminopar; Pamisyl; Parasalindon; Ferrosan; Deapasil; Apacil; Parasal; Paser; Paramycin; Gabbropas; Parasalicil; Pasnodia; Osacyl; Aminox; Pasolac; Pasmed; Propasa; Pasalon; Entepas; Pasdium; Pasara; Pamacyl; Pasem; Pasa; 2-Hydroxy-4-aminobenzoic acid; PASK; APAS; Para-Pas; Sanipirol-4; Hellipidyl; Pascorbic; PAS-C; Benzoic acid, 4-amino-2-hydroxy-; PAS (acid); Aminosalicylic Acid Resin Complex; Aminosalicylate Sodium

Indication

Disease Entry	ICD 11	Status	REF
Crohn disease	DD70	Approved	[1]
Inflammatory bowel disease	DD72	Approved	[2]
Pulmonary and extrapulmonary tuberculosis	1B10.Z	Approved	[2]
Pulmonary tuberculosis	1B10.Z	Approved	[1]
Ulcerative colitis	DD71	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 153.14
  Logarithm of the Partition Coefficient (xlogp); 1.3
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Elimination: 2% of drug is excreted from urine in the unchanged form [3]
  Metabolism: The drug is metabolized via the hepatic []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1306.00525 micromolar/kg/day [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 142.85 mg/mL [3]
• Chemical Identifiers:
  Formula: C7H7NO3
  IUPAC Name: 4-amino-2-hydroxybenzoic acid
  Canonical SMILES: C1=CC(=C(C=C1N)O)C(=O)O
  InChI: InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11)
  InChIKey: WUBBRNOQWQTFEX-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4649
  ChEBI ID: CHEBI:27565
  CAS Number: 65-49-6
  DrugBank ID: DB00233
  TTD ID: D01WJL
  VARIDT ID: DR01160
  INTEDE ID: DR1748
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dihydrofolate reductase (DHFR)	TTYZVDJ	DYR_HUMAN	Modulator	[5]
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Modulator	[5]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Modulator	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Sodium-coupled neutral amino acid transporter 3 (SLC38A3)	DTKWJH3	S38A3_HUMAN	Substrate	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
N-acetyltransferase 2 (NAT2) Main DME	DER7TA0	ARY2_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Gene/Protein Processing	[8]
Arylamine N-acetyltransferase 1 (NAT1)	OTCCNQ3H	ARY1_HUMAN	Biotransformations	[9]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Gene/Protein Processing	[8]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Gene/Protein Processing	[8]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Gene/Protein Processing	[8]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Gene/Protein Processing	[8]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Gene/Protein Processing	[8]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Gene/Protein Processing	[8]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Gene/Protein Processing	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Crohn disease
• ICD Disease Classification: DD70

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin G/H synthase 2 (COX-2)	DTT	PTGS2	2.03E-07	1.68	3.86
Prostaglandin G/H synthase 1 (COX-1)	DTT	PTGS1	4.06E-03	-0.9	-2.26
Sodium-coupled neutral amino acid transporter 3 (SLC38A3)	DTP	SNAT3	1.97E-01	-1.70E-01	-3.65E-01
N-acetyltransferase 2 (NAT2)	DME	NAT2	1.27E-04	-1.50E+00	-3.00E+00

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Aminosalicylic Acid (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[10]
Thioguanine	DM7NKEV	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Thioguanine.	Acute myeloid leukaemia [2A60]	[11]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[12]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[13]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Cannabidiol.	Epileptic encephalopathy [8A62]	[14]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[15]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[17]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[18]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[19]
Methotrexate	DM2TEOL	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Methotrexate.	Leukaemia [2A60-2B33]	[14]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Idelalisib.	Mature B-cell leukaemia [2A82]	[20]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Clofarabine.	Mature B-cell lymphoma [2A85]	[21]
Prilocaine	DMI7DZ2	Major	Increased risk of methemoglobinemia by the combination of Aminosalicylic acid and Prilocaine.	Pain [MG30-MG3Z]	[22]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Leflunomide.	Rheumatoid arthritis [FA20]	[18]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[14]
Epirubicin	DMPDW6T	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Epirubicin.	Solid tumour/cancer [2A00-2F9Z]	[10]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Aminosalicylic acid and Naltrexone.	Substance abuse [6C40]	[23]

References

• [1] Aminosalicylic acid FDA Label
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] BDDCS applied to over 900 drugs
• [4] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Identification of amino acids imparting acceptor substrate selectivity to human arylamine acetyltransferases NAT1 and NAT2. Biochem J. 2000 May 15;348 Pt 1:159-66.
• [7] Importance of the evaluation of N-acetyltransferase enzyme activity prior to 5-aminosalicylic acid medication for ulcerative colitis. Inflamm Bowel Dis. 2016 Aug;22(8):1793-802.
• [8] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [9] Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol. 2005 Jan 15;69(2):347-59. doi: 10.1016/j.bcp.2004.09.014. Epub 2004 Nov 24.
• [10] Cerner Multum, Inc. "Australian Product Information.".
• [11] Product Information. Aubagio (teriflunomide). Genzyme Corporation, Cambridge, MA.
• [12] Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
• [13] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [14] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [15] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
• [16] Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3. [PMID: 23763943]
• [17] Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
• [18] Canadian Pharmacists Association.
• [19] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
• [20] Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
• [21] Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
• [22] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [23] Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.