DT-Web

DB00859 - Penicillamine


Identification
Name Penicillamine
Accession Number DB00859 (APRD01171)
Type small molecule
Description 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 149.211
Groups approved
Monoisotopic Weight 149.051049291
Pharmacology
Indication For treatment of Wilson's disease, cystinuria and active rheumatoid arthritis.
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.
Absorption rapidly but incompletely
Protein binding >80% (bound to plasma proteins)
Biotransformation Hepatic
Route of elimination Excretion is mainly renal, mainly as disulfides.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Digoxin Penicillamine decreases the effect of digoxin
Iron Dextran The multivalent agent decreases the effect of penicillamine
Food Interactions
  • Food reduces availability, take on an empty stomach.
  • Drink liberally.

Targets


Copper
Name Copper
Gene Name Not Available
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
DTHybrid score Not Available

Transporters


Solute carrier organic anion transporter family member 1B1
Name Solute carrier organic anion transporter family member 1B1
Gene Name SLCO1B1
Actions substrate
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. - Pubmed
DTHybrid score 0.1619

Predictions


Id Partner name Gene Name Score
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0642
1588 Multidrug resistance protein 1 ABCB1 0.0364
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0362
4512 Cytochrome P450 3A4 CYP3A4 0.0336
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0312
4924 Cytochrome P450 2C8 CYP2C8 0.0303
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0272
4757 Cytochrome P450 2C9 CYP2C9 0.0234
6016 Cytochrome P450 2C19 CYP2C19 0.0215
4118 Cytochrome P450 3A5 CYP3A5 0.0207
1729 Solute carrier family 22 member 6 SLC22A6 0.0192
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0183
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.018
4200 Cytochrome P450 1A2 CYP1A2 0.018
587 Serum albumin ALB 0.0175
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0171
6142 Solute carrier family 22 member 8 SLC22A8 0.017
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0167
4119 Cytochrome P450 2D6 CYP2D6 0.0152
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0145
6107 Cytochrome P450 3A7 CYP3A7 0.0143
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0134
862 Multidrug resistance-associated protein 1 ABCC1 0.0129
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0127
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0127
6030 Cytochrome P450 2B6 CYP2B6 0.0121
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0119
3587 Gastrotropin FABP6 0.0118
70 Type-1 angiotensin II receptor AGTR1 0.0117
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0115
6145 Solute carrier family 22 member 1 SLC22A1 0.0111
2164 Multidrug resistance-associated protein 4 ABCC4 0.0104
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0102
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0102
758 Thyroid hormone receptor alpha THRA 0.0098
776 Bile salt export pump ABCB11 0.0092
346 Thyroid hormone receptor beta-1 THRB 0.0087
6024 Cytochrome P450 1A1 CYP1A1 0.0086
6141 Sodium/bile acid cotransporter SLC10A1 0.0086
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0085
80 Peroxisome proliferator-activated receptor alpha PPARA 0.0084
5880 Thrombopoietin receptor MPL 0.0081
1024 Solute carrier family 22 member 11 SLC22A11 0.0074
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0073
20 Prostaglandin G/H synthase 1 PTGS1 0.0069
731 HIV-1 protease HIV-1 protease 0.0069
833 Organic cation/carnitine transporter 1 SLC22A4 0.0064
594 Thyroxine-binding globulin SERPINA7 0.0063
6167 Organic solute transporter subunit beta OSTB 0.006
6166 Organic solute transporter subunit alpha OSTA 0.006
118 Organic cation/carnitine transporter 2 SLC22A5 0.0056
26 Vascular endothelial growth factor receptor 3 FLT4 0.0055
32 Vascular endothelial growth factor receptor 1 FLT1 0.0053
6143 Solute carrier family 22 member 7 SLC22A7 0.0053
275 Arachidonate 5-lipoxygenase ALOX5 0.0051
4604 Liver carboxylesterase 1 CES1 0.0051
806 Sodium/potassium-transporting ATPase alpha-1 chain ATP1A1 0.0047
738 Monocarboxylate transporter 1 SLC16A1 0.0044
1457 Long-chain-fatty-acid--CoA ligase 4 ACSL4 0.0044
407 Vascular endothelial growth factor receptor 2 KDR 0.0043
6148 Multidrug resistance-associated protein 7 ABCC10 0.0043
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0042
1502 Peroxisome proliferator-activated receptor delta PPARD 0.004
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.004
373 Transthyretin TTR 0.0039
563 Thyroid peroxidase TPO 0.0038
385 Potassium-transporting ATPase alpha chain 1 ATP4A 0.0038
40 RAF proto-oncogene serine/threonine-protein kinase RAF1 0.0036
199 Monocarboxylate transporter 8 SLC16A2 0.0036
2539 Tubulin alpha-1 chain TUBA4A 0.0035
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0035
890 Niemann-Pick C1-like protein 1 NPC1L1 0.0035
4148 Serine/threonine-protein kinase mTOR MTOR 0.0035
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0034
6144 Solute carrier family 22 member 2 SLC22A2 0.0034
511 5-hydroxytryptamine 1F receptor HTR1F 0.0034
1525 Heparin-binding growth factor 2 FGF2 0.0033
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0033
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0032
29 Tubulin beta-1 chain TUBB1 0.0032
6013 Cytochrome P450 2E1 CYP2E1 0.0032
1760 Aminopeptidase N ANPEP 0.0032
6843 Aminopeptidase N pepN 0.0032
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0031
698 B-Raf proto-oncogene serine/threonine-protein kinase BRAF 0.0031
33 Cystine/glutamate transporter SLC7A11 0.003
117 Sterol O-acyltransferase 1 SOAT1 0.003
636 Mitochondrial carnitine/acylcarnitine carrier protein SLC25A20 0.0029
109 Mitochondrial carnitine/acylcarnitine carrier protein CACL SLC25A29 0.0029
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0029
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0029
6136 Multidrug resistance-associated protein 5 ABCC5 0.0029
768 FK506-binding protein 1A FKBP1A 0.0029
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0029
136 Estrogen receptor ESR1 0.0027
468 Cytochrome P450 4A11 CYP4A11 0.0026
6168 Solute carrier family 22 member 16 SLC22A16 0.0026
6151 Monocarboxylate transporter 10 SLC16A10 0.0026
412 Peroxisomal carnitine O-octanoyltransferase CROT 0.0026
200 Carnitine O-palmitoyltransferase 2, mitochondrial CPT2 0.0025
551 Carnitine O-acetyltransferase CRAT 0.0025
451 Carnitine O-palmitoyltransferase I, liver isoform CPT1A 0.0025
492 Histamine H1 receptor HRH1 0.0025
3856 Fibroblast growth factor receptor 3 FGFR3 0.0025
725 5-hydroxytryptamine 1D receptor HTR1D 0.0024
1630 Integrin beta-2 ITGB2 0.0024
885 5-hydroxytryptamine 1B receptor HTR1B 0.0024
2450 Tyrosine-protein kinase ITK/TSK ITK 0.0024
3941 Amine oxidase [flavin-containing] A MAOA 0.0024
5718 Cytochrome P450 2A6 CYP2A6 0.0023
3809 Estrogen-related receptor gamma ESRRG 0.0022
320 5-hydroxytryptamine 1A receptor HTR1A 0.0022
102 DNA topoisomerase I, mitochondrial TOP1MT 0.0021
1898 Cytochrome P450 1B1 CYP1B1 0.002
6044 Serum paraoxonase/lactonase 3 PON3 0.002
6147 Solute carrier family 22 member 3 SLC22A3 0.002
950 Alpha platelet-derived growth factor receptor PDGFRA 0.002
572 Integrin alpha-L ITGAL 0.0018
228 Beta platelet-derived growth factor receptor PDGFRB 0.0018
421 Calcium signal-modulating cyclophilin ligand CAMLG 0.0018
3868 Calcineurin subunit B isoform 2 PPP3R2 0.0018
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0018
796 Inosine-5'-monophosphate dehydrogenase 2 IMPDH2 0.0018
1353 DNA topoisomerase 1 TOP1 0.0018
3552 DNA topoisomerase 1 topA 0.0018
838 Inosine-5'-monophosphate dehydrogenase 1 IMPDH1 0.0018
267 Plasminogen activator inhibitor 1 SERPINE1 0.0017
504 Mast/stem cell growth factor receptor KIT 0.0017
3811 Cytochrome P450 19A1 CYP19A1 0.0017
760 Fibroblast growth factor 1 FGF1 0.0017
1757 Myeloperoxidase MPO 0.0017
4122 Histone deacetylase 2 HDAC2 0.0017
3947 Xanthine dehydrogenase/oxidase XDH 0.0016
6221 Steroid hormone receptor ERR1 ESRRA 0.0016
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0015
751 Potassium channel subfamily K member 6 KCNK6 0.0015
6002 Prostaglandin E2 receptor EP4 subtype PTGER4 0.0015
1524 Peptidyl-prolyl cis-trans isomerase A PPIA 0.0014
6700 Peptidyl-prolyl cis-trans isomerase A ppiA 0.0014
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0014
172 Potassium channel subfamily K member 1 KCNK1 0.0014
5818 Folate receptor alpha FOLR1 0.0014
6220 Aryl hydrocarbon receptor AHR 0.0014
4131 Prostaglandin E2 receptor, EP3 subtype PTGER3 0.0014
406 Prostaglandin E2 receptor, EP2 subtype PTGER2 0.0014
2391 Ferrochelatase hemH 0.0014
6502 Ferrochelatase DKFZp686P18130 0.0014
1591 Ferrochelatase, mitochondrial FECH 0.0014
6149 Solute carrier family 22 member 10 SLC22A10 0.0014
6206 DNA-directed RNA polymerase subunit beta' rpoC 0.0013
284 DNA-directed RNA polymerase beta chain rpoB 0.0012
5773 DNA-directed RNA polymerase beta chain rpoB 0.0012
293 Gamma-glutamyl hydrolase GGH 0.0012
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0012
6495 Cytochrome c oxidase subunit 7C, mitochondrial COX7C 0.0012
6499 Cytochrome c oxidase polypeptide 7A1, mitochondrial COX7A1 0.0012
6496 Cytochrome c oxidase subunit 8A, mitochondrial COX8A 0.0012
6493 Cytochrome c oxidase subunit 6C COX6C 0.0012
6494 Cytochrome c oxidase subunit 7B, mitochondrial COX7B 0.0012
6491 Cytochrome c oxidase subunit 5A, mitochondrial COX5A 0.0012
6498 Cytochrome c oxidase subunit 6B1 COX6B1 0.0012
6489 Cytochrome c oxidase subunit 4 isoform 1, mitochondrial COX4I1 0.0012
6497 Cytochrome c oxidase subunit 6A2, mitochondrial COX6A2 0.0012
5793 Cytochrome c oxidase subunit 2 MT-CO2 0.0012
6559 Cytochrome c oxidase subunit 2 ctaC 0.0012
6669 Cytochrome c oxidase subunit 2 ctaC 0.0012
6490 Cytochrome c oxidase subunit 3 MT-CO3 0.0012
371 Cytochrome c oxidase subunit 1 MT-CO1 0.0012
6558 Cytochrome c oxidase subunit 1 ctaD 0.0012
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0011
3923 Cholinesterase BCHE 0.0011
1650 Heme carrier protein 1 SLC46A1 0.0011
2540 Choloylglycine hydrolase cbh 0.0011
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0011
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0011
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0011
6085 Fatty acid-binding protein, intestinal FABP2 0.001
6501 Fatty acid-binding protein, liver FABP1 0.001
3810 Catechol O-methyltransferase COMT 0.001
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.001
6031 Cytochrome P450 3A43 CYP3A43 0.001
952 Dipeptidyl peptidase 4 DPP4 0.0009
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0009
3917 Methylenetetrahydrofolate reductase MTHFR 0.0009
756 Sex hormone-binding globulin SHBG 0.0009
6500 Phospholipase A2 PLA2G1B 0.0008
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0008
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0008
6020 Aldehyde oxidase AOX1 0.0008
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0008
24 Thymidylate synthase TMP1 0.0008
359 Thymidylate synthase TYMS 0.0008
2626 Thymidylate synthase thyA 0.0008
2729 Thymidylate synthase thyA 0.0008
5352 Thymidylate synthase THYA 0.0008
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0008
869 Estrogen receptor beta ESR2 0.0008
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0008
365 Dihydrofolate reductase DHFR 0.0008
2381 Dihydrofolate reductase DFR1 0.0008
2833 Dihydrofolate reductase Not Available 0.0008
2931 Dihydrofolate reductase folA 0.0008
3544 Dihydrofolate reductase folA 0.0008
3682 Dihydrofolate reductase folA 0.0008
6642 Dihydrofolate reductase folA 0.0008
6756 Dihydrofolate reductase dfrA 0.0008
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0008
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0008
517 Alcohol dehydrogenase 1C ADH1C 0.0007
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0007
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0007
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0006
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0006
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0006
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0006
6106 Cytochrome P450 2C18 CYP2C18 0.0006
824 Sodium-dependent serotonin transporter SLC6A4 0.0005
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