DT-Web

DB00650 - Leucovorin


Identification
Name Leucovorin
Accession Number DB00650 (APRD00698)
Type small molecule
Description The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 473.4393
Groups approved
Monoisotopic Weight 473.165896125
Pharmacology
Indication For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
Mechanism of action As leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favoring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate). Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.
Absorption Following oral administration, leucovorin is rapidly absorbed. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg, and 37% for 100 mg.
Protein binding ~15%
Biotransformation Hepatic and intestinal mucosal, the main metabolite being the active 5-methyltetrahydrofolate. Leucovorin is readily converted to another reduced folate, 5,10-methylenetetrahydrofolate, which acts to stabilize the binding of fluorodeoxyridylic acid to thymidylate synthase and thereby enhances the inhibition of this enzyme.
Route of elimination Not Available
Toxicity LD50>8000 mg/kg (orally in rats). Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Glucarpidase Do not administer leucovorin within 2 hours of glucarpidase due to the fact that leucovorin is degraded by glucarpidase.
Trimethoprim The efficacy of Trimethoprim may be reduced by Leucovorin (folinic acid). The antibiotic, Trimethoprim, acts by blocking bacterial folic acid metabolism. Leucovorin may reduce the efficacy of Trimethoprim by providing an alternate source of folic acid. The therapeutic effect of Trimethoprim should be closely monitored.
Food Interactions Not Available

Targets


Thymidylate synthase
Name Thymidylate synthase
Gene Name TYMS
Pharmacological action yes
Actions inhibitor
References
  • Aschele C, Debernardis D, Bandelloni R, Cascinu S, Catalano V, Giordani P, Barni S, Turci D, Drudi G, Lonardi S, Gallo L, Maley F, Monfardini S: Thymidylate synthase protein expression in colorectal cancer metastases predicts for clinical outcome to leucovorin-modulated bolus or infusional 5-fluorouracil but not methotrexate-modulated bolus 5-fluorouracil. Ann Oncol. 2002 Dec;13(12):1882-92. - Pubmed
  • Zhu AX, Puchalski TA, Stanton VP Jr, Ryan DP, Clark JW, Nesbitt S, Charlat O, Kelly P, Kreconus E, Chabner BA, Supko JG: Dihydropyrimidine dehydrogenase and thymidylate synthase polymorphisms and their association with 5-fluorouracil/leucovorin chemotherapy in colorectal cancer. Clin Colorectal Cancer. 2004 Feb;3(4):225-34. - Pubmed
  • Smorenburg CH, Peters GJ, van Groeningen CJ, Noordhuis P, Smid K, van Riel AM, Dercksen W, Pinedo HM, Giaccone G: Phase II study of tailored chemotherapy for advanced colorectal cancer with either 5-fluouracil and leucovorin or oxaliplatin and irinotecan based on the expression of thymidylate synthase and dihydropyrimidine dehydrogenase. Ann Oncol. 2006 Jan;17(1):35-42. Epub 2005 Oct 26. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.6078

Transporters


Multidrug resistance-associated protein 4
Name Multidrug resistance-associated protein 4
Gene Name ABCC4
Actions inhibitor
References
  • Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. - Pubmed
DTHybrid score 0.2057
Canalicular multispecific organic anion transporter 1
Name Canalicular multispecific organic anion transporter 1
Gene Name ABCC2
Actions substrate,inhibitor
References
  • Horikawa M, Kato Y, Tyson CA, Sugiyama Y: The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents: probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites. Drug Metab Pharmacokinet. 2002;17(1):23-33. - Pubmed
  • Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. - Pubmed
DTHybrid score 0.2344
Canalicular multispecific organic anion transporter 2
Name Canalicular multispecific organic anion transporter 2
Gene Name ABCC3
Actions substrate
References
  • Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. - Pubmed
  • Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. - Pubmed
DTHybrid score 0.164

Predictions


Id Partner name Gene Name Score
24 Thymidylate synthase TMP1 0.6078
2626 Thymidylate synthase thyA 0.6078
2729 Thymidylate synthase thyA 0.6078
5352 Thymidylate synthase THYA 0.6078
1588 Multidrug resistance protein 1 ABCB1 0.0935
3639 Thymidine phosphorylase deoA 0.0837
3936 Thymidine phosphorylase TYMP 0.0837
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0789
4757 Cytochrome P450 2C9 CYP2C9 0.0721
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0706
862 Multidrug resistance-associated protein 1 ABCC1 0.0702
4512 Cytochrome P450 3A4 CYP3A4 0.0674
1729 Solute carrier family 22 member 6 SLC22A6 0.0625
4924 Cytochrome P450 2C8 CYP2C8 0.0609
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0601
6136 Multidrug resistance-associated protein 5 ABCC5 0.0555
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0481
365 Dihydrofolate reductase DHFR 0.0471
2381 Dihydrofolate reductase DFR1 0.0471
2833 Dihydrofolate reductase Not Available 0.0471
2931 Dihydrofolate reductase folA 0.0471
3544 Dihydrofolate reductase folA 0.0471
3682 Dihydrofolate reductase folA 0.0471
6642 Dihydrofolate reductase folA 0.0471
6756 Dihydrofolate reductase dfrA 0.0471
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.047
6142 Solute carrier family 22 member 8 SLC22A8 0.0454
6148 Multidrug resistance-associated protein 7 ABCC10 0.0445
776 Bile salt export pump ABCB11 0.0443
4118 Cytochrome P450 3A5 CYP3A5 0.037
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0363
587 Serum albumin ALB 0.0363
4200 Cytochrome P450 1A2 CYP1A2 0.0359
6143 Solute carrier family 22 member 7 SLC22A7 0.0343
6107 Cytochrome P450 3A7 CYP3A7 0.0331
6016 Cytochrome P450 2C19 CYP2C19 0.0331
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0317
6141 Sodium/bile acid cotransporter SLC10A1 0.0313
6137 Multidrug resistance-associated protein 6 ABCC6 0.0287
6030 Cytochrome P450 2B6 CYP2B6 0.0284
6013 Cytochrome P450 2E1 CYP2E1 0.0279
1024 Solute carrier family 22 member 11 SLC22A11 0.027
4773 Deoxycytidine kinase DCK 0.0261
2320 Thymidine kinase, cytosolic TK1 0.0255
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0253
290 Prostaglandin G/H synthase 2 PTGS2 0.0248
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0248
4604 Liver carboxylesterase 1 CES1 0.0237
87 Hypoxanthine-guanine phosphoribosyltransferase HPRT1 0.0236
4119 Cytochrome P450 2D6 CYP2D6 0.0234
3611 Cytidine deaminase cdd 0.0234
3707 Cytidine deaminase cdd 0.0234
4211 Cytidine deaminase CDA 0.0234
1302 Dihydropyrimidine dehydrogenase [NADP+] DPYD 0.023
3917 Methylenetetrahydrofolate reductase MTHFR 0.0229
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0228
20 Prostaglandin G/H synthase 1 PTGS1 0.0227
5626 Nucleoside diphosphate kinase B NME2 0.0223
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0222
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.0214
5718 Cytochrome P450 2A6 CYP2A6 0.021
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0205
6144 Solute carrier family 22 member 2 SLC22A2 0.0202
6145 Solute carrier family 22 member 1 SLC22A1 0.0192
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0187
1650 Heme carrier protein 1 SLC46A1 0.0185
293 Gamma-glutamyl hydrolase GGH 0.0184
5294 Nucleoside diphosphate kinase A NME1 0.0179
702 UMP-CMP kinase CMPK1 0.0177
738 Monocarboxylate transporter 1 SLC16A1 0.017
1043 Trifunctional purine biosynthetic protein adenosine-3 [Includes: Phosphoribosylamine--glycine ligase GART 0.0165
118 Organic cation/carnitine transporter 2 SLC22A5 0.0162
70 Type-1 angiotensin II receptor AGTR1 0.0158
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0156
13 Aminomethyltransferase, mitochondrial AMT 0.0154
6147 Solute carrier family 22 member 3 SLC22A3 0.0153
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0148
817 DNA topoisomerase 2-alpha TOP2A 0.0147
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0145
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0143
4226 Uridine phosphorylase 2 UPP2 0.0136
1898 Cytochrome P450 1B1 CYP1B1 0.0134
908 Glutathione S-transferase theta-1 GSTT1 0.0133
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0132
6171 Solute carrier family 28 member 3 SLC28A3 0.0129
2567 Thymidylate synthase thyX thyX 0.0128
4275 PCZA361.16 Not Available 0.0128
4276 DNA polymerase III subunit epsilon dnaQ 0.0128
2410 Deoxyuridine 5'-triphosphate nucleotidohydrolase dut 0.0127
2490 Deoxyuridine 5'-triphosphate nucleotidohydrolase dut 0.0127
6024 Cytochrome P450 1A1 CYP1A1 0.0127
4225 Uridine phosphorylase 1 UPP1 0.0127
6167 Organic solute transporter subunit beta OSTB 0.0118
6166 Organic solute transporter subunit alpha OSTA 0.0118
6085 Fatty acid-binding protein, intestinal FABP2 0.0117
299 Folate receptor beta FOLR2 0.0117
718 Folate receptor gamma FOLR3 0.0117
804 Mitochondrial folate transporter/carrier SLC25A32 0.0116
413 Amidophosphoribosyltransferase PPAT 0.0115
2515 Amidophosphoribosyltransferase purF 0.0115
3714 Amidophosphoribosyltransferase purF 0.0115
2555 Pol polyprotein pol 0.0114
3242 Pol polyprotein gag-pol 0.0114
3471 Pol polyprotein gag-pro-pol 0.0114
5256 Pol polyprotein pol 0.0114
6469 Pol polyprotein gag-pol 0.0114
6565 Pol polyprotein Not Available 0.0114
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0114
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0114
477 DNA topoisomerase 4 subunit A parC 0.0113
886 DNA topoisomerase 4 subunit A parC 0.0113
6226 DNA topoisomerase 4 subunit A parC 0.0113
404 DNA gyrase subunit A gyrA 0.0111
6224 DNA gyrase subunit A gyrA 0.0111
136 Estrogen receptor ESR1 0.0108
3947 Xanthine dehydrogenase/oxidase XDH 0.0108
2443 Azurin azu 0.0108
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0106
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0106
6149 Solute carrier family 22 member 10 SLC22A10 0.0106
904 Glutathione S-transferase P GSTP1 0.0105
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0104
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0099
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0098
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0098
2251 Thymidylate kinase tmk 0.0098
2254 Thymidylate kinase DTYMK 0.0098
3522 Thymidylate kinase tmk 0.0098
3478 Glucose-1-phosphate thymidylyltransferase rmlA 0.0097
4277 Glucose-1-phosphate thymidylyltransferase rmlA 0.0097
3587 Gastrotropin FABP6 0.0096
5818 Folate receptor alpha FOLR1 0.0094
890 Niemann-Pick C1-like protein 1 NPC1L1 0.0094
6106 Cytochrome P450 2C18 CYP2C18 0.0093
6020 Aldehyde oxidase AOX1 0.0093
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0092
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0092
33 Cystine/glutamate transporter SLC7A11 0.0091
677 Choline-phosphate cytidylyltransferase A PCYT1A 0.0089
686 Aldo-keto reductase family 1 member C2 AKR1C2 0.0088
468 Cytochrome P450 4A11 CYP4A11 0.0088
360 Ribonucleoside-diphosphate reductase large subunit RRM1 0.0087
509 Thymidine kinase TK 0.0085
570 Thymidine kinase TK 0.0085
2559 Thymidine kinase TK 0.0085
3430 Thymidine kinase tdk 0.0085
3518 Thymidine kinase TK 0.0085
5301 Thymidine kinase tdk 0.0085
5771 Thymidine kinase ORF36 0.0085
7009 Thymidine kinase ORF36 0.0085
406 Prostaglandin E2 receptor, EP2 subtype PTGER2 0.0084
5691 DTDP-4-DEHYDRORHAMNOSE 3,5-EPIMERASE RMLC rmlC 0.0084
3361 Serpin B5 SERPINB5 0.0084
5694 Transcription antiterminator licT licT 0.0084
1435 Synaptic vesicle glycoprotein 2A SV2A 0.0084
1760 Aminopeptidase N ANPEP 0.0083
6843 Aminopeptidase N pepN 0.0083
850 Vasopressin V1b receptor AVPR1B 0.0081
117 Sterol O-acyltransferase 1 SOAT1 0.0081
896 Glutathione S-transferase Mu 1 GSTM1 0.0081
26 Vascular endothelial growth factor receptor 3 FLT4 0.008
1141 Sialidase-1 NEU1 0.008
64 Neuraminidase NA 0.008
641 Neuraminidase NA 0.008
2676 Neuraminidase NA 0.008
3026 Neuraminidase NA 0.008
3519 Neuraminidase NA 0.008
6007 Neuraminidase NA 0.008
165 FL cytokine receptor FLT3 0.008
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0079
1405 Thiopurine S-methyltransferase TPMT 0.0078
32 Vascular endothelial growth factor receptor 1 FLT1 0.0077
204 cGMP-specific 3',5'-cyclic phosphodiesterase PDE5A 0.0076
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0076
161 Tubulin beta chain TUBB 0.0075
312 Tubulin beta chain TUB2 0.0075
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0075
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0074
275 Arachidonate 5-lipoxygenase ALOX5 0.0073
228 Beta platelet-derived growth factor receptor PDGFRB 0.0072
1648 Elastin ELN 0.0072
342 P protein [Includes: DNA-directed DNA polymerase P 0.0072
612 P protein [Includes: DNA-directed DNA polymerase P 0.0072
6165 Copper-transporting ATPase 1 ATP7A 0.0071
6163 Copper-transporting ATPase 2 ATP7B 0.0071
185 Vasopressin V1a receptor AVPR1A 0.0071
2417 Chloramphenicol acetyltransferase cat 0.0071
3278 Chloramphenicol acetyltransferase cat 0.0071
322 Vasopressin V2 receptor AVPR2 0.007
1313 Lactoylglutathione lyase GLO1 0.0069
6146 High affinity copper uptake protein 1 SLC31A1 0.0068
2298 Cytochrome P450-cam camC 0.0068
56 Delta-aminolevulinic acid dehydratase ALAD 0.0067
2356 Delta-aminolevulinic acid dehydratase hemB 0.0067
3613 Delta-aminolevulinic acid dehydratase hemB 0.0067
3674 Delta-aminolevulinic acid dehydratase hemB 0.0067
504 Mast/stem cell growth factor receptor KIT 0.0067
4152 Superoxide dismutase [Cu-Zn] SOD1 0.0066
614 Progesterone receptor PGR 0.0064
2539 Tubulin alpha-1 chain TUBA4A 0.0063
6218 Pannexin-1 PANX1 0.0063
2286 Isocitrate dehydrogenase [NADP] icd 0.0063
2302 Isocitrate dehydrogenase [NADP] icd 0.0063
2771 Isocitrate dehydrogenase [NADP] icd 0.0063
3811 Cytochrome P450 19A1 CYP19A1 0.0063
5482 Sialidase-2 NEU2 0.0062
3270 Elongation factor G fusA 0.0062
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0062
6161 Probable low affinity copper uptake protein 2 SLC31A2 0.0062
3685 Catabolite gene activator crp 0.0061
407 Vascular endothelial growth factor receptor 2 KDR 0.0061
4655 Adenylate cyclase cyaC 0.0061
4759 Adenylate cyclase cyaB2 0.0061
4534 Cytohesin-2 CYTH2 0.0061
2808 Chloramphenicol acetyltransferase 3 cat3 0.0061
833 Organic cation/carnitine transporter 1 SLC22A4 0.006
3668 Maltose-binding periplasmic protein precursor malE 0.0059
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0058
4192 DNA topoisomerase 2-beta TOP2B 0.0058
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0057
695 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A PDE10A 0.0057
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0056
2347 Proto-oncogene serine/threonine-protein kinase Pim-1 PIM1 0.0056
6042 Prostaglandin reductase 2 PTGR2 0.0056
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0056
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0056
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0055
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0055
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0055
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0054
2981 Phospholipase A2, membrane associated PLA2G2A 0.0053
2592 Beta-galactosidase lacZ 0.0053
1757 Myeloperoxidase MPO 0.0052
4760 Mll3241 protein mll3241 0.0052
2391 Ferrochelatase hemH 0.0052
6502 Ferrochelatase DKFZp686P18130 0.0052
1591 Ferrochelatase, mitochondrial FECH 0.0052
489 Monocarboxylate transporter 2 SLC16A7 0.0052
6043 Putative G-protein coupled receptor 44 GPR44 0.0052
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.005
315 Arginase-1 ARG1 0.005
5849 cAMP-dependent protein kinase type I-alpha regulatory subunit PRKAR1A 0.0049
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.0049
6033 High affinity interleukin-8 receptor A CXCR1 0.0049
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0049
421 Calcium signal-modulating cyclophilin ligand CAMLG 0.0049
3868 Calcineurin subunit B isoform 2 PPP3R2 0.0049
950 Alpha platelet-derived growth factor receptor PDGFRA 0.0048
951 Macrophage colony-stimulating factor 1 receptor CSF1R 0.0048
1198 Serum paraoxonase/arylesterase 1 PON1 0.0047
6223 Penicillin-binding protein 1C pbpC 0.0047
3957 Adenosine deaminase ADA 0.0047
273 Apoptosis regulator Bcl-2 BCL2 0.0046
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0046
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0046
6496 Cytochrome c oxidase subunit 8A, mitochondrial COX8A 0.0045
6495 Cytochrome c oxidase subunit 7C, mitochondrial COX7C 0.0045
6499 Cytochrome c oxidase polypeptide 7A1, mitochondrial COX7A1 0.0045
6497 Cytochrome c oxidase subunit 6A2, mitochondrial COX6A2 0.0045
6494 Cytochrome c oxidase subunit 7B, mitochondrial COX7B 0.0045
6493 Cytochrome c oxidase subunit 6C COX6C 0.0045
6498 Cytochrome c oxidase subunit 6B1 COX6B1 0.0045
6491 Cytochrome c oxidase subunit 5A, mitochondrial COX5A 0.0045
6489 Cytochrome c oxidase subunit 4 isoform 1, mitochondrial COX4I1 0.0045
5793 Cytochrome c oxidase subunit 2 MT-CO2 0.0045
6559 Cytochrome c oxidase subunit 2 ctaC 0.0045
6669 Cytochrome c oxidase subunit 2 ctaC 0.0045
6490 Cytochrome c oxidase subunit 3 MT-CO3 0.0045
371 Cytochrome c oxidase subunit 1 MT-CO1 0.0045
6558 Cytochrome c oxidase subunit 1 ctaD 0.0045
2038 Inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB 0.0044
6172 ATP-binding cassette sub-family B member 8, mitochondrial ABCB8 0.0042
1629 Transcription factor AP-1 JUN 0.0041
2540 Choloylglycine hydrolase cbh 0.0041
731 HIV-1 protease HIV-1 protease 0.0041
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.004
385 Potassium-transporting ATPase alpha chain 1 ATP4A 0.004
2180 3-phosphoinositide-dependent protein kinase 1 PDPK1 0.004
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.004
3810 Catechol O-methyltransferase COMT 0.004
6263 cAMP-dependent protein kinase catalytic subunit alpha PRKACA 0.004
6501 Fatty acid-binding protein, liver FABP1 0.0039
4120 NADPH--cytochrome P450 reductase POR 0.0038
2232 Interleukin-5 IL5 0.0037
260 Cytochrome P450 51 ERG11 0.0037
761 Cytochrome P450 51 ERG11 0.0037
3163 Cytochrome P450 51 cyp51 0.0037
1593 Mucin-2 MUC2 0.0037
1524 Peptidyl-prolyl cis-trans isomerase A PPIA 0.0037
6700 Peptidyl-prolyl cis-trans isomerase A ppiA 0.0037
4034 Glutaredoxin-1 GLRX 0.0037
1928 Leukotriene C4 synthase LTC4S 0.0037
4037 Hypothetical protein GPX1 0.0037
4297 Hypothetical protein SP_1951 0.0037
4521 Hypothetical protein BC_2969 0.0037
4540 Hypothetical protein TM_1070 0.0037
4555 Hypothetical protein MT1739 0.0037
4569 Hypothetical protein mshD 0.0037
4578 Hypothetical protein PA3270 0.0037
4747 Hypothetical protein PA3967 0.0037
5177 Hypothetical protein TM_0096 0.0037
5194 Hypothetical protein PA1204 0.0037
5240 Hypothetical protein Rv2991 0.0037
5370 Hypothetical protein TM_1158 0.0037
5710 Hypothetical protein Tb927.5.1360 0.0037
4043 Glutaredoxin-2, mitochondrial GLRX2 0.0037
4029 Microsomal glutathione S-transferase 3 MGST3 0.0037
907 Glutathione peroxidase 2 GPX2 0.0037
4032 Microsomal glutathione S-transferase 1 MGST1 0.0037
4030 Thioredoxin domain-containing protein 12 TXNDC12 0.0037
910 Epididymal secretory glutathione peroxidase GPX5 0.0037
903 Glutathione S-transferase A5 GSTA5 0.0037
4039 CDNA FLJ23636 fis, clone CAS07176 GPX8 0.0037
4036 Glutathione peroxidase 6 GPX6 0.0037
4040 Glutathione peroxidase 7 GPX7 0.0037
911 Glutathione peroxidase 3 GPX3 0.0037
906 Glutathione peroxidase 1 GPX1 0.0037
4035 Glutathione S-transferase Mu 5 GSTM5 0.0037
900 Glutathione S-transferase A4 GSTA4 0.0037
4033 S-formylglutathione hydrolase ESD 0.0037
4038 Glutathione peroxidase 4 GPX4 0.0037
1975 Phospholipid hydroperoxide glutathione peroxidase, mitochondrial GPX4 0.0037
4042 Glutathione transferase omega-2 GSTO2 0.0037
1056 Gamma-glutamyltranspeptidase 1 GGT1 0.0037
6038 Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma PDE6H 0.0036
1787 Nuclear factor NF-kappa-B p105 subunit NFKB1 0.0036
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.0035
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.0035
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.0035
6168 Solute carrier family 22 member 16 SLC22A16 0.0035
3809 Estrogen-related receptor gamma ESRRG 0.0035
461 Glycine receptor subunit alpha-3 GLRA3 0.0035
6206 DNA-directed RNA polymerase subunit beta' rpoC 0.0035
6037 Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma PDE6G 0.0034
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0034
6031 Cytochrome P450 3A43 CYP3A43 0.0034
3319 Hydroxyacylglutathione hydrolase HAGH 0.0033
898 Glutathione S-transferase A3 GSTA3 0.0033
897 Glutathione S-transferase kappa 1 GSTK1 0.0033
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0033
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0033
5923 Microtubule-associated protein tau MAPT 0.0033
5924 Microtubule-associated protein 4 MAP4 0.0033
6500 Phospholipase A2 PLA2G1B 0.0033
909 Maleylacetoacetate isomerase GSTZ1 0.0033
4217 Telomerase reverse transcriptase TERT 0.0032
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0032
284 DNA-directed RNA polymerase beta chain rpoB 0.0032
5773 DNA-directed RNA polymerase beta chain rpoB 0.0032
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0032
905 Glutathione transferase omega-1 GSTO1 0.0032
899 Glutathione S-transferase Mu 3 GSTM3 0.0032
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0032
4041 Microsomal glutathione S-transferase 2 MGST2 0.0031
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0031
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0031
1123 Eosinophil cationic protein RNASE3 0.0031
131 Synaptic vesicular amine transporter SLC18A2 0.0031
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0031
78 Acetyl-CoA acetyltransferase, mitochondrial ACAT1 0.0031
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0031
1852 Microtubule-associated protein 2 MAP2 0.0031
40 RAF proto-oncogene serine/threonine-protein kinase RAF1 0.0031
6220 Aryl hydrocarbon receptor AHR 0.003
3923 Cholinesterase BCHE 0.003
115 Penicillin-binding protein 2 mrdA 0.003
6069 Penicillin-binding protein 2 mrdA 0.003
6118 Penicillin-binding protein 2 penA 0.003
6187 Penicillin-binding protein 2 pbpA 0.003
6686 Penicillin-binding protein 2 pbp2 0.003
6939 Penicillin-binding protein 2 mrdA 0.003
7163 Penicillin-binding protein 2 pbpA 0.003
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.003
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.003
737 Mineralocorticoid receptor NR3C2 0.003
2165 Glutathione S-transferase Mu 2 GSTM2 0.0029
4177 Proto-oncogene tyrosine-protein kinase receptor ret RET 0.0029
517 Alcohol dehydrogenase 1C ADH1C 0.0029
207 Glutathione synthetase GSS 0.0029
5269 Glutathione synthetase gshB 0.0029
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0029
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0029
777 Tumor necrosis factor TNF 0.0028
543 Penicillin-binding protein 1B mrcB 0.0028
6186 Penicillin-binding protein 1B ponB 0.0028
6822 Penicillin-binding protein 1b pbp1b 0.0028
6844 Penicillin-binding protein 1b pbp1b 0.0028
476 RAC-alpha serine/threonine-protein kinase AKT1 0.0028
1 Peptidoglycan synthetase ftsI ftsI 0.0028
4155 Peptidoglycan synthetase ftsI ftsI 0.0028
7 Nitric oxide synthase, inducible NOS2 0.0028
645 Penicillin-binding protein 1A mrcA 0.0028
5805 Penicillin-binding protein 1A ponA 0.0028
6185 Penicillin-binding protein 1A mrcA 0.0028
6799 Penicillin-binding protein 1A pbpA 0.0028
465 Calmodulin CALM1 0.0028
901 Glutathione S-transferase Mu 4 GSTM4 0.0027
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0027
778 Cysteinyl leukotriene receptor 1 CYSLTR1 0.0027
3854 Basic fibroblast growth factor receptor 1 FGFR1 0.0027
1569 G1/S-specific cyclin-D1 CCND1 0.0027
29 Tubulin beta-1 chain TUBB1 0.0026
2021 Thrombomodulin THBD 0.0026
698 B-Raf proto-oncogene serine/threonine-protein kinase BRAF 0.0026
3932 Glutathione S-transferase A2 GSTA2 0.0025
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.0025
4031 Glutathione S-transferase A1 GSTA1 0.0025
2101 Glutathione-requiring prostaglandin D synthase HPGDS 0.0024
6211 Tubulin epsilon chain TUBE1 0.0024
6210 Tubulin delta chain TUBD1 0.0024
6212 Tubulin gamma-1 chain TUBG1 0.0024
146 Androgen receptor AR 0.0024
714 Glutathione reductase, mitochondrial GSR 0.0024
76 Nitric-oxide synthase, brain NOS1 0.0023
1714 Mitogen-activated protein kinase 3 MAPK3 0.0022
3610 Thioredoxin reductase 1, cytoplasmic TXNRD1 0.0021
6002 Prostaglandin E2 receptor EP4 subtype PTGER4 0.0021
824 Sodium-dependent serotonin transporter SLC6A4 0.002
558 Solute carrier family 12 member 1 SLC12A1 0.002
291 Nitric-oxide synthase, endothelial NOS3 0.002
4095 Neuronal acetylcholine receptor subunit alpha-7 CHRNA7 0.002
947 Neuronal acetylcholine receptor subunit alpha-4 CHRNA4 0.002
918 Glutamate receptor, ionotropic kainate 2 GRIK2 0.002
1630 Integrin beta-2 ITGB2 0.002
952 Dipeptidyl peptidase 4 DPP4 0.0019
6836 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial HIBCH 0.0019
6837 Serine/threonine-protein kinase 17B STK17B 0.0019
4131 Prostaglandin E2 receptor, EP3 subtype PTGER3 0.0019
841 Gamma-aminobutyric-acid receptor subunit alpha-6 GABRA6 0.0018
921 Glutamate receptor 2 GRIA2 0.0018
3920 Methylenetetrahydrofolate reductase intermediate form MTHFR 0.0018
3763 5,10-methylenetetrahydrofolate reductase metF 0.0018
3918 5,10-methylenetetrahydrofolate reductase MTHFR 0.0018
5094 5,10-methylenetetrahydrofolate reductase metF 0.0018
59 AMT protein AMT 0.0018
3919 Methionyl-tRNA formyltransferase, mitochondrial MTFMT 0.0018
1202 10-formyltetrahydrofolate dehydrogenase ALDH1L1 0.0018
530 Gamma-aminobutyric-acid receptor subunit alpha-4 GABRA4 0.0018
1792 Tissue-type plasminogen activator PLAT 0.0018
389 Amiloride-sensitive cation channel 2, neuronal ACCN2 0.0018
1176 Mitogen-activated protein kinase 1 MAPK1 0.0018
2449 Tubulin alpha-3 chain TUBA1A 0.0017
102 DNA topoisomerase I, mitochondrial TOP1MT 0.0017
523 Gamma-aminobutyric-acid receptor subunit alpha-5 GABRA5 0.0017
580 Gamma-aminobutyric-acid receptor subunit alpha-3 GABRA3 0.0017
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.0017
4162 Potassium voltage-gated channel subfamily KQT member 3 KCNQ3 0.0017
6656 UDP-glucuronosyltransferase 3A1 UGT3A1 0.0017
6044 Serum paraoxonase/lactonase 3 PON3 0.0016
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0016
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0016
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.0016
296 Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial MTHFD2 0.0015
6599 HTH-type transcriptional regulator ttgR ttgR 0.0015
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0015
572 Integrin alpha-L ITGAL 0.0015
2599 Tyrosine-protein kinase HCK HCK 0.0015
838 Inosine-5'-monophosphate dehydrogenase 1 IMPDH1 0.0014
796 Inosine-5'-monophosphate dehydrogenase 2 IMPDH2 0.0014
357 Carbonic anhydrase 2 CA2 0.0014
1353 DNA topoisomerase 1 TOP1 0.0014
3552 DNA topoisomerase 1 topA 0.0014
3884 SHMT2 protein SHMT2 0.0014
3901 SHMT2 protein SHMT2 0.0014
3885 Hypothetical protein DKFZp686P09201 DKFZp686P09201 0.0014
3879 Serine hydroxymethyltransferase 2 Not Available 0.0014
321 Serine hydroxymethyltransferase, mitochondrial SHMT2 0.0014
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0014
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0014
6344 ATP synthase subunit gamma, mitochondrial ATP5C1 0.0014
6343 ATP synthase subunit beta, mitochondrial ATP5B 0.0014
6342 ATP synthase subunit alpha, mitochondrial ATP5A1 0.0014
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0014
4122 Histone deacetylase 2 HDAC2 0.0014
679 C-1-tetrahydrofolate synthase, cytoplasmic MTHFD1 0.0013
809 Methionine synthase MTR 0.0013
2935 Methionine synthase metH 0.0013
367 Serine hydroxymethyltransferase, cytosolic SHMT1 0.0012
751 Potassium channel subfamily K member 6 KCNK6 0.0012
6259 (3R)-hydroxymyristoyl-acyl carrier protein dehydratase fabZ 0.0012
2404 Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform PIK3CG 0.0012
172 Potassium channel subfamily K member 1 KCNK1 0.0011
340 Apoptotic protease-activating factor 1 APAF1 0.0011
84 Nuclear receptor 0B1 NR0B1 0.0011
1192 Sulfotransferase 1A1 SULT1A1 0.0011
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.001
469 Annexin A1 ANXA1 0.001
373 Transthyretin TTR 0.001
825 Arsenical pump-driving ATPase ASNA1 0.001
3435 Arsenical pump-driving ATPase arsA 0.001
486 Serine/threonine-protein kinase ALS2CR7 CDK15 0.001
510 Serine/threonine-protein kinase receptor R3 ACVRL1 0.001
2105 ATP-binding cassette sub-family G member 1 ABCG1 0.001
745 Anti-Muellerian hormone type-2 receptor AMHR2 0.001
483 A-Raf proto-oncogene serine/threonine-protein kinase ARAF 0.001
733 Activin receptor type 1B ACVR1B 0.001
154 AFG3-like protein 2 AFG3L2 0.001
225 NEDD8-activating enzyme E1 regulatory subunit NAE1 0.001
21 Beta-adrenergic receptor kinase 2 ADRBK2 0.001
377 Beta-adrenergic receptor kinase 1 ADRBK1 0.001
395 ALK tyrosine kinase receptor Not Available 0.001
292 Activin receptor type-1 ACVR1 0.0009
849 Activated CDC42 kinase 1 TNK2 0.0009
380 Cytochrome P450 17A1 CYP17A1 0.0009
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0009
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0009
821 Acetyl-coenzyme A synthetase 2-like, mitochondrial ACSS1 0.0009
704 Long-chain-fatty-acid--CoA ligase 1 ACSL1 0.0009
386 Acetyl-coenzyme A synthetase, cytoplasmic ACSS2 0.0009
297 Adenylate cyclase type 1 ADCY1 0.0009
289 Cytosolic purine 5'-nucleotidase NT5C2 0.0008
484 Tyrosine-protein kinase ABL2 ABL2 0.0008
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0008
740 Argininosuccinate synthase ASS1 0.0007
865 Argininosuccinate synthase ASS1 0.0007
2680 Argininosuccinate synthase argG 0.0007
3194 Argininosuccinate synthase argG 0.0007
869 Estrogen receptor beta ESR2 0.0007
6021 Adenosine kinase ADK 0.0007
661 ADP/ATP translocase 1 SLC25A4 0.0007
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0007
871 Glucocorticoid receptor NR3C1 0.0006
17 Proto-oncogene tyrosine-protein kinase ABL1 ABL1 0.0006
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