Details of the Drug

General Information of Drug (ID: DMQ7UL8)

• Drug Name: Camostat
• Synonyms: Camostat; 59721-28-7; camostate; Camostat [INN]; Camostatum [INN-Latin]; UNII-0FD207WKDU; CCRIS 7219; 4-(2-(2-(Dimethylamino)-2-oxoethoxy)-2-oxoethyl)phenyl 4-guanidinobenzoate; 0FD207WKDU; C20H22N4O5; Camostat (INN); Foipan; FOY 305; FOY-305; Dimethylcarbamoylmethyl 4-(4-guqnidinobenzoyloxy)phenylacetat; foypan; Camostatum; CHEMBL85164; camostate-mesilate; [4-[2-[2-(dimethylamino)-2-oxoethoxy]-2-oxoethyl]phenyl] 4-(diaminomethylideneamino)benzoate; p-Guanidinobenzoic acid, ester with (p-hydroxyphenyl)acetic acid, ester with N

Indication

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Phase 2	[1], [2], [3], [4]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 398.4
  Topological Polar Surface Area (xlogp); 1.1
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 10,400 +/- 1,400 mcgmin/L [5]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 87.1 +/- 29.5 mcg/L [5]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 40 min [5]
  Clearance: The clearance of drug is 4.5-7.3 mL/min/kg [6]
  Elimination: Camostat mesylate is 89.8-95.6% eliminated in the urine and 1.0-1.7% eliminated in the feces [6]
  Half-life: The concentration or amount of drug in body reduced by one-half in 3.8 - 4.7 hours [6]
  Metabolism: The drug is metabolized via the carboxyesterate to the active 4-(4-guanidinobenzoyloxy) phenylacetate [6]
  Vd: The volume of distribution (Vd) of drug is 0.34-1.31 L/kg [6]
• Chemical Identifiers:
  Formula: C20H22N4O5
  IUPAC Name: [4-[2-[2-(dimethylamino)-2-oxoethoxy]-2-oxoethyl]phenyl] 4-(diaminomethylideneamino)benzoate
  Canonical SMILES: CN(C)C(=O)COC(=O)CC1=CC=C(C=C1)OC(=O)C2=CC=C(C=C2)N=C(N)N
  InChI: InChI=1S/C20H22N4O5/c1-24(2)17(25)12-28-18(26)11-13-3-9-16(10-4-13)29-19(27)14-5-7-15(8-6-14)23-20(21)22/h3-10H,11-12H2,1-2H3,(H4,21,22,23)
  InChIKey: XASIMHXSUQUHLV-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 2536
  ChEBI ID: CHEBI:135632
  CAS Number: 59721-28-7
  DrugBank ID: DB13729
  TTD ID: D0Y6SQ
  VARIDT ID: DR00883

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serine protease unspecific (SP)	TTEMV5X	NOUNIPROTAC	Inhibitor	[7]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[8]

References

• [1] 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: 6432).
• [2] Effect of a specific serine protease inhibitor on the rat pancreas: systemic administration of camostate and exocrine pancreatic secretion. Digestion. 1984;30(3):171-8.
• [3] Effects of the serine protease inhibitors FOY and FOY 305 on phospholipase A1 (EC 3.1.1.32) activity in rat - liver lysosomes. Pharmacol Res Commun. 1983 May;15(5):451-9.
• [4] Camostat, an oral trypsin inhibitor, reduces pancreatic fibrosis induced by repeated administration of a superoxide dismutase inhibitor in rats. J Gastroenterol Hepatol. 2005 Jun;20(6):895-9.
• [5] Ono Pharmaceutical: Foipan Camostat Mesilate Oral Tablets
• [6] Metabolic fate of 14C-camostat mesylate in man, rat and dog after intravenous administration. Xenobiotica. 1994 Jan;24(1):79-92. doi: 10.3109/00498259409043223.
• [7] Camostat mesilate inhibits prostasin activity and reduces blood pressure and renal injury in salt-sensitive hypertension. J Hypertens. 2009 Jan;27(1):181-9.
• [8] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [9] Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
• [10] Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86.
• [11] Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
• [12] Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
• [13] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [14] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [15] Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
• [16] Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
• [17] Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.
• [18] Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
• [19] Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients. Int J Oncol. 2009 Jul;35(1):115-20.
• [20] Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding Clin Trials. 2005;2(3):218-29; discussion 229-32.
• [21] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [22] Viral Serpin Therapeutics: From Concept to Clinic. Methods Enzymol. 2011; 499: 301-329.
• [23] Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant. Gan To Kagaku Ryoho. 1996 Dec;23(14):1971-9.
• [24] New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
• [25] US patent application no. 2005,0096,323, Diketopiperazine derivatives to inhibit thrombin.
• [26] Thrombin inhibition in an ex vivo model of porcine heart xenograft hyperacute rejection. Transplantation. 1996 Mar 27;61(6):862-8.