Penicillamine - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (1)Transporters (1)

Targets (1)Transporters (1)Biointeractions (1)

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

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

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

External IDs

NSC-81549

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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	Oral	Valeant Canada Lp Valeant Canada S.E.C.	1964-12-31	Not applicable	Canada
Depen	Tablet	250 mg/1	Oral	Meda Pharmaceuticals Ltd	1978-11-30	Not applicable	US
Depen Tab 250mg	Tablet	250 mg	Oral	Carter Horner Corp.	1981-12-31	2003-08-19	Canada

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Atamir	Sandoz

Brand mixtures

Not Available

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][[email protected]](N)(C(O)=O)C(C)(C)S

Pharmacology

Indication

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

Structured Indications

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	Kind	Pharmacological action	Actions	Organism	UniProt ID
Copper	Small molecule	yes	chelator	Human	not applicable	details

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	Drug group
Aluminum hydroxide	The serum concentration of Penicillamine can be decreased when it is combined with Aluminum hydroxide.	Approved
Bismuth Subcitrate	The serum concentration of Penicillamine can be decreased when it is combined with Bismuth Subcitrate.	Approved
Calcium Carbonate	The serum concentration of Penicillamine can be decreased when it is combined with Calcium carbonate.	Approved
Digoxin	The serum concentration of Digoxin can be decreased when it is combined with Penicillamine.	Approved
Eltrombopag	The serum concentration of Penicillamine can be increased when it is combined with Eltrombopag.	Approved
Ferric Carboxymaltose	Ferric Carboxymaltose can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved
Ferric Citrate	Ferric Citrate can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved
Ferric pyrophosphate	Ferric pyrophosphate can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved
Iron	Iron can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved
Iron Dextran	Iron Dextran can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved, Vet Approved
Iron saccharate	Iron saccharate can cause a decrease in the absorption of Penicillamine resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved
Magaldrate	The serum concentration of Penicillamine can be decreased when it is combined with Magaldrate.	Withdrawn
Magnesium carbonate	The serum concentration of Penicillamine can be decreased when it is combined with Magnesium carbonate.	Approved
Magnesium Hydroxide	The serum concentration of Penicillamine can be decreased when it is combined with Magnesium hydroxide.	Approved
Magnesium oxide	The serum concentration of Penicillamine can be decreased when it is combined with Magnesium oxide.	Approved
Magnesium Trisilicate	The serum concentration of Penicillamine can be decreased when it is combined with Magnesium Trisilicate.	Approved
Polaprezinc	The serum concentration of Penicillamine can be decreased when it is combined with Polaprezinc.	Approved
Teriflunomide	The serum concentration of Penicillamine can be increased when it is combined with Teriflunomide.	Approved

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

Resource	Link
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
Drug Product Database	10302
RxList	http://www.rxlist.com/cgi/generic3/penicillamine.htm
Drugs.com	http://www.drugs.com/cdi/penicillamine.html
Wikipedia	Penicillamine

ATC Codes

M01CC01 — Penicillamine

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Download (264 KB)

MSDS

Download (71.7 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Completed	Treatment	Brain and Central Nervous System Tumors	1
2	Recruiting	Treatment	Arteriovenous fistula occlusion	1
Not Available	No Longer Available	Not Available	Scleroderma	1

Pharmacoeconomics

Manufacturers

Aton pharma inc
Meda pharmaceuticals inc

Packagers

Dosage forms

Form	Route	Strength
Capsule	Oral	125 mg
Capsule	Oral	250 mg/1
Capsule	Oral	250 mg
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 Type	Description	Splash Key
GC-MS	GC-MS Spectrum - GC-EI-TOF	splash10-0fr5-1930000000-6ee8522d7087601d49e6	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF	splash10-00di-9520000000-1ac6006c4f882c72292b	View in MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF	splash10-00di-9640000000-736237ccaaa4ef171daa	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities 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

Chemical entities

Super Class

Organic compounds

Class

Organic acids and derivatives

Sub Class

Carboxylic acids and derivatives

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

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

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

penicillamine (CHEBI:7959 )

Targets

Details

1. Copper

Kind: Small molecule
Organism: Human
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

Details

1. Solute carrier organic anion transporter family member 1B1

Kind: Protein
Organism: Human
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, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
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 September 01, 2017 10:33

Structure for DB00859 (Penicillamine)

Targets

References

Transporters

References