Details of the Drug

General Information of Drug (ID: DMA17D0)

Drug Name
Dorzolamide
Synonyms
Trusopt; Dorzolamide (DZA); Dorzolamide (INN); Trusopt (TN); (4S,6S)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide; (4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide; (4S,6S)-4-Ethylamino-6-methyl-7,7-dioxo-4,5,6,7-tetrahydro-7lambda*6*-thieno[2,3-b]thiopyran-2-sulfonic acid amide; (4S,trans)-4-(ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide; (4S-TRANS)-4-(ETHYLAMINO)-5,6-DIHYDRO-6-METHYL-4H-THIENO(2,3-B)THIOPYRAN-2-SULFONAMIDE-7,7-DIOXIDE
Indication
Disease Entry ICD 11 Status REF
Ocular hypertension 9C61.01 Approved [1]
Open-angle glaucoma 9C61 Approved [2]
Therapeutic Class
Antihypertensive Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 324.4
Logarithm of the Partition Coefficient (xlogp) 0.4
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Elimination
10% of drug is excreted from urine in the unchanged form [3]
Half-life
The concentration or amount of drug in body reduced by one-half in more than 4 months [4]
Metabolism
The drug is metabolized via the liver [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.08221 micromolar/kg/day [5]
Water Solubility
The ability of drug to dissolve in water is measured as 3.9 mg/mL [3]
Chemical Identifiers
Formula
C10H16N2O4S3
IUPAC Name
(4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide
Canonical SMILES
CCN[C@H]1C[C@@H](S(=O)(=O)C2=C1C=C(S2)S(=O)(=O)N)C
InChI
InChI=1S/C10H16N2O4S3/c1-3-12-8-4-6(2)18(13,14)10-7(8)5-9(17-10)19(11,15)16/h5-6,8,12H,3-4H2,1-2H3,(H2,11,15,16)/t6-,8-/m0/s1
InChIKey
IAVUPMFITXYVAF-XPUUQOCRSA-N
Cross-matching ID
PubChem CID
5284549
ChEBI ID
CHEBI:4702
CAS Number
120279-96-1
DrugBank ID
DB00869
TTD ID
D05UYW
INTEDE ID
DR0536

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Carbonic anhydrase II (CA-II) TTANPDJ CAH2_HUMAN Inhibitor [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2E1 (CYP2E1)
Main DME 		DEVDYN7 CP2E1_HUMAN Substrate [8]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Ocular hypertension
ICD Disease Classification 9C61.01
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Carbonic anhydrase II (CA-II) DTT CA2 7.95E-08 0.52 0.33
Cytochrome P450 2E1 (CYP2E1) DME CYP2E1 1.91E-13 6.46E-02 3.30E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 1.07E-11 -1.16E-01 -2.53E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.87E-03 -6.67E-02 -2.12E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dorzolamide (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Aspirin DM672AH Major Increased plasma concentration of Dorzolamide and Aspirin due to competitive binding of plasma proteins. Pain [MG30-MG3Z] [9]
Choline salicylate DM8P137 Major Increased risk of metabolic acidosis by the combination of Dorzolamide and Choline salicylate. Postoperative inflammation [1A00-CA43] [9]
Salsalate DM13P4C Major Increased plasma concentration of Dorzolamide and Salsalate due to competitive binding of plasma proteins. Rheumatoid arthritis [FA20] [9]
Salicyclic acid DM2F8XZ Major Increased risk of metabolic acidosis by the combination of Dorzolamide and Salicyclic acid. Seborrhoeic dermatitis [EA81] [9]

References

1 Dorzolamide FDA Label
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: 6810).
3 BDDCS applied to over 900 drugs
4 FDA Approved Drug Products: TRUSOPT (dorzolamide hydrochloride) ophthalmic solution
5 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
6 Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8.
7 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
8 In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Drug Metab Dispos. 1994 Nov-Dec;22(6):916-21.
9 Cowan RA, Hartnell GG, Lowdell CP, Baird IM, Leak AM "Metabolic acidosis induced by carbonic anhydrase inhibitors and salicylates in patients with normal renal function." Br Med J (Clin Res Ed) 289 (1984): 347-8. [PMID: 6432091]