Details of the Drug

General Information of Drug (ID: DM40EF6)

Drug Name
Penicillamine
Synonyms
D-Penicillamine; penicillamine; 52-67-5; Cuprimine; D-(-)-Penicillamine; 3-Mercapto-D-valine; Depen; Cuprenil; D-Penamine; (-)-Penicillamine; (2S)-2-Amino-3-methyl-3-sulfanylbutanoic acid; D-Mercaptovaline; Mercaptovaline; Perdolat; Penicillamin; Pendramine; Kuprenil; Depamine; Mercaptyl; Trolovol; Metalcaptase; Artamine; Cupripen; (S)-3,3-Dimethylcysteine; D-Valine, 3-mercapto-; Penicillaminum; Penicilamina; Sufirtan; beta-Thiovaline; Dimethylcysteine; D-beta,beta-Dimethylcysteine; D-3-Mercaptovaline; beta,beta-Dimethylcysteine; Penicillamina; Penicilllamine; Sufortan; Copper penicillaminate; D Penicillamine; Penicillamina [DCIT]; Reduced penicillamine; D 3 Mercaptovaline; TBB068824; Beta,beta Dimethylcysteine; Beta-Thiovaline; Cuprimine (TN); D-Penicilamine; D-Penicyllamine; Depen (TN); P-1280; Penicilamina [INN-Spanish]; Penicillaminate, Copper; Penicillaminum [INN-Latin]; Reduced D-penicillamine; Beta,beta-Dimethylcysteine; D,3-Mercaptovaline; D-beta-Mercaptovaline; Distamine (*Hydrochloride*); Metalcaptase (*Hydrochloride*); Penicillamine (JAN/USP/INN); Penicillamine [USAN:INN:BAN:JAN]; Alpha-Amino-beta-methyl-beta-mercaptobutyric acid; D-(-)-2-Amino-3-mercapto-3-methylbutanoic acid; (2S)-2-amino-3-methyl-3-sulfanyl-butanoic acid; (D)-PENICILLAMINE; (S)-Penicillamin; (S)-Penicillamine; 2-Amino-3-mercapto-3-methylbutanoic acid; 3,3-Dimethyl-D-cysteine; 3-Mercaptovaline; 3-sulfanyl-D-valine; D-penicillamine
Indication
Disease Entry ICD 11 Status REF
Cystinuria 5C60.2 Approved [1]
Rheumatoid arthritis FA20 Approved [2]
Wilson disease 5C64.00 Investigative [1]
Therapeutic Class
Antidotes
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 149.21
Logarithm of the Partition Coefficient (xlogp) -1.8
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Absorption
The drug is rapidly but incompletely absorbed []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Clearance
The drug present in the plasma can be removed from the body at the rate of 10.65 mL/min/kg [4]
Elimination
45% 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 1 hours [4]
Metabolism
The drug is metabolized via the hepatic []
Unbound Fraction
The unbound fraction of drug in plasma is 0.12% [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.26 L/kg [4]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Congenital, familial and genetic disorders Not Available COL1A1 OTI31178 [5]
Dermatomyositis Not Available HLA-B OTGPIQEH [5]
Dermatomyositis Not Available HLA-B18 OTO1T7OA [5]
Dermatomyositis Not Available HLA-DR4 OTR8MHXB [5]
Drug toxicity Not Available HLA-DRB1 OTZ84GNP [5]
Chemical Identifiers
Formula
C5H11NO2S
IUPAC Name
(2S)-2-amino-3-methyl-3-sulfanylbutanoic acid
Canonical SMILES
CC(C)([C@H](C(=O)O)N)S
InChI
InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1
InChIKey
VVNCNSJFMMFHPL-VKHMYHEASA-N
Cross-matching ID
PubChem CID
5852
ChEBI ID
CHEBI:7959
CAS Number
771431-20-0
DrugBank ID
DB00859
TTD ID
D08HZC
ACDINA ID
D00514
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
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
Human immunodeficiency virus Tat protein (HIV tat) TTT3ZC9 TAT_HV1H2 Inhibitor [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Biochemical Pathways [7]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Gene/Protein Processing [8]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [9]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Gene/Protein Processing [9]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Gene/Protein Processing [9]
C-C motif chemokine 4 (CCL4) OT6B8P25 CCL4_HUMAN Gene/Protein Processing [9]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Gene/Protein Processing [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Protein Interaction/Cellular Processes [11]
Catalase (CAT) OTHEBX9R CATA_HUMAN Gene/Protein Processing [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Penicillamine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Decreased renal excretion of Penicillamine caused by Remdesivir mediated nephrotoxicity. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [12]
Inotersen DMJ93CT Major Increased risk of nephrotoxicity by the combination of Penicillamine and Inotersen. Amyloidosis [5D00] [13]
Iodipamide DMXIQYS Major Increased risk of nephrotoxicity by the combination of Penicillamine and Iodipamide. Cholelithiasis [DC11] [14]
Didanosine DMI2QPE Moderate Decreased absorption of Penicillamine due to formation of complexes caused by Didanosine. Human immunodeficiency virus disease [1C60-1C62] [15]
Quinapril DMR8H31 Moderate Decreased absorption of Penicillamine due to formation of complexes caused by Quinapril. Hypertension [BA00-BA04] [13]
Probenecid DMMFWOJ Moderate Decreased renal excretion of Penicillamine caused by Probenecid. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [16]
Iron DMAP8MV Moderate Decreased absorption of Penicillamine due to formation of complexes caused by Iron. Iron deficiency anaemia [3A00] [17]
Lanthanum carbonate DMMJQSH Moderate Decreased absorption of Penicillamine due to formation of complexes caused by Lanthanum carbonate. Mineral absorption/transport disorder [5C64] [18]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Penicillamine and Ocrelizumab. Multiple sclerosis [8A40] [19]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive myelosuppressive effects by the combination of Penicillamine and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [20]
Azathioprine DMMZSXQ Moderate Additive myelosuppressive effects by the combination of Penicillamine and Azathioprine. Transplant rejection [NE84] [12]
Ganciclovir DM1MBYQ Moderate Additive myelosuppressive effects by the combination of Penicillamine and Ganciclovir. Virus infection [1A24-1D9Z] [12]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Penicillamine and Valganciclovir. Virus infection [1A24-1D9Z] [12]
⏷ Show the Full List of 13 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Quinoline yellow WS E00309 24671 Colorant
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Penicillamine 250 mg capsule 250 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Penicillamine 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: 7264).
3 BDDCS applied to over 900 drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
6 Docking studies reveal a selective binding of D-penicillamine to the transactivator protein of human immunodeficiency virus type 1. FEBS Lett. 2002 Apr 10;516(1-3):43-6.
7 Chelation and intercalation: complementary properties in a compound for the treatment of Alzheimer's disease. J Struct Biol. 2000 Jun;130(2-3):209-16. doi: 10.1006/jsbi.2000.4285.
8 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
9 D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis. Apoptosis. 2012 Oct;17(10):1079-94.
10 The influence of alclofenac treatment on acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in patients with rheumatoid arthritis. Curr Med Res Opin. 1975;3(5):286-97. doi: 10.1185/03007997509114779.
11 N-acetyl cysteine and penicillamine induce apoptosis via the ER stress response-signaling pathway. Mol Carcinog. 2010 Jan;49(1):68-74. doi: 10.1002/mc.20578.
12 Cerner Multum, Inc. "Australian Product Information.".
13 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
14 Wong GT, Lee EY, Irwin MG. Contrast induced nephropathy in vascular surgery.?Br J Anaesth. 2016;117 Suppl 2:ii63-ii73. [PMID: 27566809]
15 Haagsma CJ "Clinically important drug interactions with disease-modifying antirheumatic drugs." Drugs Aging 13 (1998): 281-9. [PMID: 9805209]
16 Yu T-F, Roboz J, Johnson S, Kaung C "Studies on the metabolism of D-penicillamine and its interaction with probenecid in cystinuria and rheumatoid arthritis." J Rheumatol 11 (1984): 467-70. [PMID: 6481720]
17 Lyle WH "Penicillamine and iron." Lancet 2 (1976): 420. [PMID: 73880]
18 Canadian Pharmacists Association.
19 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
20 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.