Identification

Name
Penicillamine
Accession Number
DB00859
Description

Penicillamine is a pharmaceutical of the chelator class. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic (it inhibits the action of pyridoxine). It is an α-amino acid metabolite of penicillin, although it has no antibiotic properties.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 149.211
Monoisotopic: 149.051049291
Chemical Formula
C5H11NO2S
Synonyms
  • (−)-penicillamine
  • (S)-2-amino-3-mercapto-3-methylbutanoic acid
  • (S)-3,3-dimethylcysteine
  • 3-mercapto-D-valine
  • D-(−)-penicillamine
  • D-penicillamine
  • D-β,β-dimethylcysteine
  • penicilamina
  • Penicillamine
External IDs
  • NSC-81549

Pharmacology

Indication

For treatment of Wilson's disease, cystinuria and active rheumatoid arthritis.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy. Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. Penicillamine inhibits macrophages, decreases IL-1 and the number of T-lymphocytes, and prevents collagen cross linkage. In Wilson's disease it binds copper, allowing it to be eliminated in the urine.

Mechanism of action

Penicillamine is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of penicillamine. Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between penicillamine and cystine, resulting in formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cystine and is excreted readily. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity.

TargetActionsOrganism
ACopper
chelator
Humans
Absorption

rapidly but incompletely

Volume of distribution
Not Available
Protein binding

>80% (bound to plasma proteins)

Metabolism

Hepatic

Route of elimination

Excretion is mainly renal, mainly as disulfides.

Half-life

1 hour

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Penicillamine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Penicillamine.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Penicillamine.
AcetylcysteineThe excretion of Penicillamine can be decreased when combined with Acetylcysteine.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Penicillamine.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Penicillamine is combined with Acipimox.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Penicillamine.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Penicillamine.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Penicillamine.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Penicillamine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Drink plenty of fluids.
  • Take on an empty stomach. Co-administration with food decreases bioavailability.

Products

International/Other Brands
Atamir (Sandoz)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CuprimineCapsule125 mgOralMerck Ltd.1980-12-312005-06-18Canada flag
CuprimineCapsuleOralBausch Health, Canada Inc.1964-12-31Not applicableCanada flag
CuprimineCapsule125 mg/1OralMerck Sharp & Dohme Limited1970-12-042009-05-31US flag
CuprimineCapsule250 mg/1OralBausch Health US, LLC1970-12-04Not applicableUS flag
CuprimineCapsule250 mg/1OralMerck Sharp & Dohme Limited1970-12-042009-05-31US flag
D-PenamineTablet125 mg/1OralMylan Pharmaceuticals Inc.2018-11-152020-06-30US flag
DepenTablet250 mg/1OralMEDA Pharmaceuticals1978-11-30Not applicableUS flag
Depen Tab 250mgTabletOralCarter Horner Corp.1981-12-312003-08-19Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PenicillamineCapsule250 1/1OralApotex Corp.2020-06-26Not applicableUS flag
PenicillamineCapsule250 mg/1OralPar Pharmaceutical, Inc.2020-01-08Not applicableUS flag
PenicillamineCapsule250 mg/1OralANI Pharmaceuticals, Inc.2019-05-07Not applicableUS flag
PenicillamineTablet, film coated250 mg/1OralPar Pharmaceutical, Inc.2020-01-02Not applicableUS flag
PenicillamineCapsule, gelatin coated250 mg/1OralDr. Reddy's Laboratories Inc.2020-08-04Not applicableUS flag
PenicillamineCapsule250 mg/1OralOceanside Pharmaceuticals1970-12-04Not applicableUS flag
PenicillamineCapsule250 mg/1OralActavis Pharma, Inc.2019-06-25Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
D-PenaminePenicillamine (125 mg/1)TabletOralMylan Pharmaceuticals Inc.2018-11-152020-06-30US flag

Categories

ATC Codes
M01CC01 — Penicillamine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resulting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Valine and derivatives
Alternative Parents
D-alpha-amino acids / Thia fatty acids / Methyl-branched fatty acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Alkylthiols / Organopnictogen compounds / Organic oxides / Monoalkylamines
show 2 more
Substituents
Aliphatic acyclic compound / Alkylthiol / Alpha-amino acid / Amine / Amino acid / Branched fatty acid / Carbonyl group / Carboxylic acid / D-alpha-amino acid / Fatty acid
show 15 more
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
penicillamine (CHEBI:7959)

Chemical Identifiers

UNII
GNN1DV99GX
CAS number
52-67-5
InChI Key
VVNCNSJFMMFHPL-VKHMYHEASA-N
InChI
InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1
IUPAC Name
(2S)-2-amino-3-methyl-3-sulfanylbutanoic acid
SMILES
[H][[email protected]](N)(C(O)=O)C(C)(C)S

References

Synthesis Reference

Manfred Klaus Joachim Bock, deceased, "Method of producing penicillamine." U.S. Patent US3968154, issued November, 1960.

US3968154
General References
  1. WALSHE JM: Penicillamine, a new oral therapy for Wilson's disease. Am J Med. 1956 Oct;21(4):487-95. [PubMed:13362281]
  2. Walshe JM: The story of penicillamine: a difficult birth. Mov Disord. 2003 Aug;18(8):853-9. [PubMed:12889074]
  3. Gong Y, Frederiksen SL, Gluud C: D-penicillamine for primary biliary cirrhosis. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004789. [PubMed:15495127]
  4. Suarez-Almazor ME, Spooner C, Belseck E: Penicillamine for rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD001460. [PubMed:10796440]
  5. Munro R, Capell HA: Penicillamine. Br J Rheumatol. 1997 Jan;36(1):104-9. [PubMed:9117147]
KEGG Drug
D00496
KEGG Compound
C07418
PubChem Compound
5852
PubChem Substance
46508305
ChemSpider
5643
BindingDB
39346
RxNav
7975
ChEBI
7959
ChEMBL
CHEMBL1430
ZINC
ZINC000000114127
Therapeutic Targets Database
DNC000575
PharmGKB
PA450840
PDBe Ligand
LEI
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Penicillamine
AHFS Codes
  • 64:00.00 — Heavy Metal Antagonists
PDB Entries
3h5g
FDA label
Download (264 KB)
MSDS
Download (71.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentCystine renal calculi1
3Active Not RecruitingTreatmentWilson's Disease1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2RecruitingTreatmentArteriovenous fistula occlusion1
0RecruitingTreatmentWilson's Disease1
Not AvailableNo Longer AvailableNot AvailableScleroderma1

Pharmacoeconomics

Manufacturers
  • Aton pharma inc
  • Meda pharmaceuticals inc
Packagers
  • Aton Pharma Inc.
  • Draxis Specialty Pharmaceuticals Inc.
  • Gallipot
  • Meda AB
  • Medisca Inc.
  • Merck & Co.
  • Patheon Inc.
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral125 mg/1
CapsuleOral125 mg
CapsuleOral250 mg/1
Capsule, coatedOral250 mg
TabletOral125 mg/1
TabletOral250 mg/1
TabletOral
CapsuleOral250 1/1
Capsule, gelatin coatedOral250 mg/1
PowderNot applicable1 g/1g
Tablet, film coatedOral250 mg/1
Prices
Unit descriptionCostUnit
Penicillamine(d-) powder8.88USD g
Cuprimine 250 mg capsule5.63USD capsule
Depen 250 mg titratab4.73USD tablet
Penicillamine powder2.81USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)198.5 °CPhysProp
water solubility1.11E+005 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-1.78HANSCH,C ET AL. (1995)
logS-0.13ADME Research, USCD
pKa1.8MERCK for CO; NH2-7.9; thiol-10.5
Predicted Properties
PropertyValueSource
Water Solubility4.65 mg/mLALOGPS
logP-1.7ALOGPS
logP-2.1ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)2.56ChemAxon
pKa (Strongest Basic)9.09ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area63.32 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity37.22 m3·mol-1ChemAxon
Polarizability14.76 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9278
Blood Brain Barrier+0.5821
Caco-2 permeable-0.7778
P-glycoprotein substrateNon-substrate0.7679
P-glycoprotein inhibitor INon-inhibitor0.9818
P-glycoprotein inhibitor IINon-inhibitor0.9959
Renal organic cation transporterNon-inhibitor0.9744
CYP450 2C9 substrateNon-substrate0.776
CYP450 2D6 substrateNon-substrate0.8636
CYP450 3A4 substrateNon-substrate0.7038
CYP450 1A2 substrateInhibitor0.8476
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9528
CYP450 2C19 inhibitorNon-inhibitor0.9187
CYP450 3A4 inhibitorNon-inhibitor0.9107
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9693
Ames testAMES toxic0.6358
CarcinogenicityNon-carcinogens0.6495
BiodegradationNot ready biodegradable0.8739
Rat acute toxicity2.0294 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9987
hERG inhibition (predictor II)Non-inhibitor0.962
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.76 KB)
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0fr5-1930000000-6ee8522d7087601d49e6
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00di-9520000000-1ac6006c4f882c72292b
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00di-9640000000-736237ccaaa4ef171daa
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Small molecule
Organism
Humans
Pharmacological action
Yes
Actions
Chelator
References
  1. Brewer GJ: Novel therapeutic approaches to the treatment of Wilson's disease. Expert Opin Pharmacother. 2006 Feb;7(3):317-24. [PubMed:16448326]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Gui C, Hagenbuch B: Role of transmembrane domain 10 for the function of organic anion transporting polypeptide 1B1. Protein Sci. 2009 Nov;18(11):2298-306. doi: 10.1002/pro.240. [PubMed:19760661]

Drug created on June 13, 2005 07:24 / Updated on September 25, 2020 15:13

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