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

Similar Structures

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
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Cuprimine	Capsule	125 mg	Oral	Merck Ltd.	1980-12-31	2005-06-18
Cuprimine	Capsule	250 mg/1	Oral	Aton Pharma, Inc.	1970-12-04	Not applicable
Cuprimine	Capsule	250 mg	Oral	Valeant Canada Lp Valeant Canada S.E.C.	1964-12-31	Not applicable
Cuprimine	Capsule	125 mg/1	Oral	Merck Sharp & Dohme Limited	1970-12-04	2009-05-31
Cuprimine	Capsule	250 mg/1	Oral	Merck Sharp & Dohme Limited	1970-12-04	2009-05-31
Cuprimine	Capsule	250 mg/1	Oral	Oceanside Pharmaceuticals, Inc.	1970-12-04	Not applicable
Depen	Tablet	250 mg/1	Oral	MEDA Pharmaceuticals	1978-11-30	Not applicable
Depen Tab 250mg	Tablet	250 mg	Oral	Carter Horner Corp.	1981-12-31	2003-08-19

Additional Data Available

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

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

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International/Other Brands

Atamir (Sandoz)

Categories

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	chelator	Humans

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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
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(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.

Additional Data Available

Extended Description

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

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Severity

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

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Evidence Level

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

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Action

Evidence Level

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

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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

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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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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
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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
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Molecular Framework: Aliphatic acyclic compounds
External Descriptors: penicillamine (CHEBI:7959)

Targets

1. Copper

Kind

Small molecule

Organism

Humans

Pharmacological action

Yes

Actions

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

Details1. Solute carrier organic anion transporter family member 1B1

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 April 24, 2019 12:02

Penicillamine

Identification

Structure for Penicillamine (DB00859)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

Transporters

References