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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyPenicillamine
Identification
- Name
- Penicillamine
- Accession Number
- DB00859 (APRD01171)
- Type
- Small Molecule
- Groups
- Approved
- 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.
- Structure
Structure for Penicillamine (DB00859)
- 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
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Cuprimine Capsule 125 mg/1 Oral Merck Sharp & Dohme Limited 1970-12-04 2009-05-31 US 
Cuprimine Capsule 250 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1964-12-31 Not applicable Canada 
Cuprimine Capsule 125 mg Oral Merck Ltd. 1980-12-31 2005-06-18 Canada Cuprimine Capsule 250 mg/1 Oral Aton Pharma, Inc. 1970-12-04 Not applicable US Cuprimine Capsule 250 mg/1 Oral Merck Sharp & Dohme Limited 1970-12-04 2009-05-31 US Depen Tablet 250 mg/1 Oral MEDA Pharmaceuticals 1978-11-30 Not applicable US Depen Tab 250mg Tablet 250 mg Oral Carter Horner Corp. 1981-12-31 2003-08-19 Canada - International/Other Brands
- Atamir (Sandoz)
- Categories
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Amino Acids, Sulfur
- Antidotes
- Antiinflammatory and Antirheumatic Products
- Chelating Agents
- Heavy Metal Antagonists
- Immunosuppressive Agents
- Musculo-Skeletal System
- Myelosuppressive Agents
- OATP1B1/SLCO1B1 Substrates
- Penicillamine and Similar Agents
- Protective Agents
- Sequestering Agents
- Specific Antirheumatic Agents
- Sulfur Compounds
- UNII
- GNN1DV99GX
- CAS number
- 52-67-5
- Weight
- Average: 149.211
Monoisotopic: 149.051049291 - Chemical Formula
- C5H11NO2S
- 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][C@](N)(C(O)=O)C(C)(C)S
Pharmacology
- Indication
For treatment of Wilson's disease, cystinuria and active rheumatoid arthritis.
- Associated Conditions
- 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. It works by reducing numbers of T-lymphocytes, inhibiting macrophage function, decreasing IL-1, decreasing rheumatoid factor, and preventing collagen from cross-linking. Its use in Wilson's disease, a rare genetic disorder of copper metabolism, relies on its binding to accumulated copper and elimination through 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.
Target Actions Organism ACopper chelatorHumans - 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
- Toxicity
- Not Available
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin The risk or severity of bleeding can be increased when (R)-warfarin is combined with Penicillamine. (S)-Warfarin The risk or severity of bleeding can be increased when (S)-Warfarin is combined with Penicillamine. 2-Methoxyethanol The risk or severity of adverse effects can be increased when Penicillamine is combined with 2-Methoxyethanol. 4-hydroxycoumarin The risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Penicillamine. 9-(N-methyl-L-isoleucine)-cyclosporin A The risk or severity of adverse effects can be increased when Penicillamine is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A. Abatacept The risk or severity of adverse effects can be increased when Penicillamine is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Penicillamine. Abetimus The risk or severity of adverse effects can be increased when Penicillamine is combined with Abetimus. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Penicillamine. Acetylcysteine The excretion of Penicillamine can be decreased when combined with Acetylcysteine. - Food Interactions
- Drink liberally.
- Food reduces availability, take on an empty stomach.
References
- Synthesis Reference
Manfred Klaus Joachim Bock, deceased, "Method of producing penicillamine." U.S. Patent US3968154, issued November, 1960.
US3968154- General References
- WALSHE JM: Penicillamine, a new oral therapy for Wilson's disease. Am J Med. 1956 Oct;21(4):487-95. [PubMed:13362281]
- Walshe JM: The story of penicillamine: a difficult birth. Mov Disord. 2003 Aug;18(8):853-9. [PubMed:12889074]
- Gong Y, Frederiksen SL, Gluud C: D-penicillamine for primary biliary cirrhosis. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004789. [PubMed:15495127]
- Suarez-Almazor ME, Spooner C, Belseck E: Penicillamine for rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD001460. [PubMed:10796440]
- Munro R, Capell HA: Penicillamine. Br J Rheumatol. 1997 Jan;36(1):104-9. [PubMed:9117147]
- External Links
- KEGG Drug
- D00496
- KEGG Compound
- C07418
- PubChem Compound
- 5852
- PubChem Substance
- 46508305
- ChemSpider
- 5643
- BindingDB
- 50217941
- ChEBI
- 7959
- ChEMBL
- CHEMBL1430
- Therapeutic Targets Database
- DNC000575
- PharmGKB
- PA450840
- HET
- LEI
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Penicillamine
- ATC Codes
- M01CC01 — 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
Phase Status Purpose Conditions Count 2 Completed Treatment Brain and Central Nervous System Tumors 1 2 Recruiting Treatment Arteriovenous fistula occlusion 1 3 Recruiting Treatment Wilson's Disease 1 Not Available No Longer Available Not Available Scleroderma 1
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
Form Route Strength Capsule Oral 125 mg/1 Capsule Oral 125 mg Capsule Oral 250 mg Capsule Oral 250 mg/1 Tablet Oral 250 mg/1 Tablet Oral 250 mg - Prices
Unit description Cost Unit Penicillamine(d-) powder 8.88USD g Cuprimine 250 mg capsule 5.63USD capsule Depen 250 mg titratab 4.73USD tablet Penicillamine powder 2.81USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 198.5 °C PhysProp water solubility 1.11E+005 mg/L (at 20 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP -1.78 HANSCH,C ET AL. (1995) logS -0.13 ADME Research, USCD pKa 1.8 MERCK for CO; NH2-7.9; thiol-10.5 - Predicted Properties
Property Value Source Water Solubility 4.65 mg/mL ALOGPS logP -1.7 ALOGPS logP -2.1 ChemAxon logS -1.5 ALOGPS pKa (Strongest Acidic) 2.56 ChemAxon pKa (Strongest Basic) 9.09 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 63.32 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 37.22 m3·mol-1 ChemAxon Polarizability 14.76 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9278 Blood Brain Barrier + 0.5821 Caco-2 permeable - 0.7778 P-glycoprotein substrate Non-substrate 0.7679 P-glycoprotein inhibitor I Non-inhibitor 0.9818 P-glycoprotein inhibitor II Non-inhibitor 0.9959 Renal organic cation transporter Non-inhibitor 0.9744 CYP450 2C9 substrate Non-substrate 0.776 CYP450 2D6 substrate Non-substrate 0.8636 CYP450 3A4 substrate Non-substrate 0.7038 CYP450 1A2 substrate Inhibitor 0.8476 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9528 CYP450 2C19 inhibitor Non-inhibitor 0.9187 CYP450 3A4 inhibitor Non-inhibitor 0.9107 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9693 Ames test AMES toxic 0.6358 Carcinogenicity Non-carcinogens 0.6495 Biodegradation Not ready biodegradable 0.8739 Rat acute toxicity 2.0294 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9987 hERG inhibition (predictor II) Non-inhibitor 0.962
Spectra
- Mass Spec (NIST)
- Download (7.76 KB)
- Spectra
Spectrum Spectrum Type Splash Key GC-MS Spectrum - GC-EI-TOF GC-MS splash10-0fr5-1930000000-6ee8522d7087601d49e6 GC-MS Spectrum - GC-EI-TOF GC-MS splash10-00di-9520000000-1ac6006c4f882c72292b GC-MS Spectrum - GC-EI-TOF GC-MS splash10-00di-9640000000-736237ccaaa4ef171daa Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- 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
- Valine or derivatives / Alpha-amino acid / D-alpha-amino acid / Branched fatty acid / Methyl-branched fatty acid / Thia fatty acid / Fatty acyl / Fatty acid / Amino acid / Alkylthiol show 15 more
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- penicillamine (CHEBI:7959)
Targets
1. Copper
Yes
Chelator
References
- 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
- 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 January 22, 2019 17:57