Identification
Name Trimetrexate
Accession Number DB01157 (APRD00268)
Type small molecule
Description A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. [PubChem]
Structure
Categories (*)
Molecular Weight 369.4176
Groups approved
Monoisotopic Weight 369.180089627
Pharmacology
Indication For use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer.
Mechanism of action In vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death.
Absorption Not Available
Protein binding 95% (over the concentration range of 18.75 to 1000 ng/mL)
Biotransformation Hepatic. Preclinical data strongly suggest that the major metabolic pathway is oxidative O-demethylation, followed by conjugation to either glucuronide or the sulfate.
Route of elimination Ten to 30% of the administered dose is excreted unchanged in the urine.
Toxicity The LD50 of intravenous trimetrexate in mice is 62 mg/kg (186 mg/m2). Myelosuppression is a dose-limiting toxic effect.
Affected organisms
  • Humans and other mammals
  • Bacteria and protozoa
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol The anticoagulant effect of Acenocoumarol, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use.
Digoxin The absorption of Digoxin, a cardiac glycoside, may be decreased by antineoplastic agents such as Trimetrexate. Liquid forms of Digoxin do not appear to be significantly affected. Monitor Digoxin tablet efficacy if Trimetrexate therapy is initiated, discontinued or if the dose is altered.
Warfarin The anticoagulant effect of Warfarin, a Vitamin K antagonist, may be altered by antineoplastics such as Trimetrexate. Monitor for changes in the anticoagulant effects of warfarin and other coumarin derivatives during concomitant use.
Food Interactions Not Available
Dihydrofolate reductase
Name Dihydrofolate reductase
Gene Name DHFR
Pharmacological action yes
Actions inhibitor
References
  • Bertino JR, Zhao SC, Mineishi S, Ercikan-Abali EA, Banerjee D: Use of variants of dihydrofolate reductase in gene transfer to produce resistance to methotrexate and trimetrexate. Prog Exp Tumor Res. 1999;36:82-94. - Pubmed
  • Graffner-Nordberg M, Kolmodin K, Aqvist J, Queener SF, Hallberg A: Design, synthesis, computational prediction, and biological evaluation of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii. J Med Chem. 2001 Jul 19;44(15):2391-402. - Pubmed
  • Warlick CA, Diers MD, Wagner JE, McIvor RS: In vivo selection of antifolate-resistant transgenic hematopoietic stem cells in a murine bone marrow transplant model. J Pharmacol Exp Ther. 2002 Jan;300(1):50-6. - Pubmed
  • Zhu WY, Bunni M, Priest DG, DiCapua JL, Dressler JM, Chen Z, Melera PW: Severe folate restriction results in depletion of and alteration in the composition of the intracellular folate pool, moderate sensitization to methotrexate and trimetrexate, upregulation of endogenous DHFR activity, and overexpression of metallothionein II and folate receptor alpha that, upon folate repletion, confer drug resistance to CHL cells. J Exp Ther Oncol. 2002 Sep-Oct;2(5):264-77. - Pubmed
  • Sweeney CL, Frandsen JL, Verfaillie CM, McIvor RS: Trimetrexate inhibits progression of the murine 32Dp210 model of chronic myeloid leukemia in animals expressing drug-resistant dihydrofolate reductase. Cancer Res. 2003 Mar 15;63(6):1304-10. - Pubmed
  • Polshakov VI, Birdsall B, Frenkiel TA, Gargaro AR, Feeney J: Structure and dynamics in solution of the complex of Lactobacillus casei dihydrofolate reductase with the new lipophilic antifolate drug trimetrexate. Protein Sci. 1999 Mar;8(3):467-81. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.053
Id Partner name Gene Name Score
2381 Dihydrofolate reductase DFR1 1.053
2833 Dihydrofolate reductase Not Available 1.053
2931 Dihydrofolate reductase folA 1.053
3544 Dihydrofolate reductase folA 1.053
3682 Dihydrofolate reductase folA 1.053
6642 Dihydrofolate reductase folA 1.053
6756 Dihydrofolate reductase dfrA 1.053
6236 Trimethoprim-sensitive dihydrofolate reductase dfrB 0.0961
1124 Sepiapterin reductase SPR 0.0413
1650 Heme carrier protein 1 SLC46A1 0.0345
24 Thymidylate synthase TMP1 0.0342
359 Thymidylate synthase TYMS 0.0342
2626 Thymidylate synthase thyA 0.0342
2729 Thymidylate synthase thyA 0.0342
5352 Thymidylate synthase THYA 0.0342
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0231
620 Bifunctional dihydrofolate reductase-thymidylate synthase Not Available 0.02
1043 Trifunctional purine biosynthetic protein adenosine-3 [Includes: Phosphoribosylamine--glycine ligase GART 0.0128
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.0126
4757 Cytochrome P450 2C9 CYP2C9 0.0123
4924 Cytochrome P450 2C8 CYP2C8 0.01
4773 Deoxycytidine kinase DCK 0.0081
4119 Cytochrome P450 2D6 CYP2D6 0.008
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.008
4512 Cytochrome P450 3A4 CYP3A4 0.0065
1588 Multidrug resistance protein 1 ABCB1 0.0051
6013 Cytochrome P450 2E1 CYP2E1 0.0037
6016 Cytochrome P450 2C19 CYP2C19 0.0033
4200 Cytochrome P450 1A2 CYP1A2 0.0032
5818 Folate receptor alpha FOLR1 0.0027
293 Gamma-glutamyl hydrolase GGH 0.0023
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0019
646 Malate dehydrogenase, cytoplasmic MDH1 0.0019
635 Estradiol 17-beta-dehydrogenase 8 HSD17B8 0.0019
666 NADP-dependent malic enzyme ME1 0.0019
6020 Aldehyde oxidase AOX1 0.0018
11 NAD(P) transhydrogenase, mitochondrial NNT 0.0018
5333 Alcohol dehydrogenase, iron-containing TM_0920 0.0018
5326 Oxidoreductase, short chain dehydrogenase/reductase family TM_0441 0.0018
5346 Oxidoreductase, aldo/keto reductase family TM_1009 0.0018
5332 MtdA bifunctional protein mtdA 0.0018
4403 Protein iolS iolS 0.0018
5322 Oxidoreductase ydhF ydhF 0.0018
3772 3-oxoacyl-[acyl-carrier-protein] reductase fabG 0.0018
5157 Dehydrogenase/reductase SDR family member 11 DHRS11 0.0018
5342 NADH-dependent butanol dehydrogenase, putative TM_0820 0.0018
5343 NADP-dependent fatty aldehyde dehydrogenase aldH 0.0018
5330 General stress protein 69 yhdN 0.0018
3778 NAD(P) transhydrogenase subunit beta pntB 0.0018
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0017
4484 2,5-diketo-D-gluconic acid reductase A dkgA 0.0017
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0016
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0016
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0016
679 C-1-tetrahydrofolate synthase, cytoplasmic MTHFD1 0.0016
686 Aldo-keto reductase family 1 member C2 AKR1C2 0.0016
3917 Methylenetetrahydrofolate reductase MTHFR 0.0016
4582 Putative pteridine reductase 2 ptr2 0.0016
2375 ADP-L-glycero-D-manno-heptose-6-epimerase hldD 0.0016
5075 Sulfite reductase [NADPH] flavoprotein alpha-component cysJ 0.0016
5073 Ferredoxin--NADP reductase petH 0.0016
5076 Ferredoxin--NADP reductase fpr 0.0016
5119 Ferredoxin--NADP reductase petH 0.0016
5121 Ferredoxin--NADP reductase fpr 0.0016
5328 Prostaglandin F synthase Tb11.02.2310 0.0016
989 L-xylulose reductase DCXR 0.0016
3446 NADP-dependent alcohol dehydrogenase adh 0.0016
1799 Glucose-6-phosphate 1-dehydrogenase G6PD 0.0016
2630 Glucose-6-phosphate 1-dehydrogenase zwf 0.0016
2636 Shikimate dehydrogenase aroE 0.0016
3515 Shikimate dehydrogenase aroE 0.0016
2305 Isocitrate dehydrogenase [NADP] cytoplasmic IDH1 0.0016
4628 NADP-dependent glyceraldehyde-3-phosphate dehydrogenase gapN 0.0016
2286 Isocitrate dehydrogenase [NADP] icd 0.0016
2302 Isocitrate dehydrogenase [NADP] icd 0.0016
2771 Isocitrate dehydrogenase [NADP] icd 0.0016
654 Flavin reductase BLVRB 0.0016
738 Monocarboxylate transporter 1 SLC16A1 0.0015
139 Aldo-keto reductase family 1 member C1 AKR1C1 0.0015
6148 Multidrug resistance-associated protein 7 ABCC10 0.0015
217 Estradiol 17-beta-dehydrogenase 1 HSD17B1 0.0015
6862 Aldo-keto reductase family 1 member B10 AKR1B10 0.0015
6297 Prostaglandin reductase 1 PTGR1 0.0015
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0015
4531 Putative ketoacyl reductase actIII 0.0015
444 Alcohol dehydrogenase 1B ADH1B 0.0015
3062 Aspartate-semialdehyde dehydrogenase asd 0.0014
5325 2,4-dienoyl-CoA reductase, mitochondrial DECR1 0.0014
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0014
2675 Pteridine reductase 1 PTR1 0.0014
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0014
3573 2,4-dienoyl-CoA reductase [NADPH] fadH 0.0014
364 Corticosteroid 11-beta-dehydrogenase isozyme 1 HSD11B1 0.0014
2159 Quinone oxidoreductase CRYZ 0.0013
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0013
822 Aldose reductase AKR1B1 0.0013
1024 Solute carrier family 22 member 11 SLC22A11 0.0012
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0012
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0012
2164 Multidrug resistance-associated protein 4 ABCC4 0.0012
6143 Solute carrier family 22 member 7 SLC22A7 0.0012
862 Multidrug resistance-associated protein 1 ABCC1 0.0012
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0012
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0011
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0011
6142 Solute carrier family 22 member 8 SLC22A8 0.0011
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0011
587 Serum albumin ALB 0.001
1729 Solute carrier family 22 member 6 SLC22A6 0.001
76 Nitric-oxide synthase, brain NOS1 0.0009
4120 NADPH--cytochrome P450 reductase POR 0.0009
816 Biliverdin reductase A BLVRA 0.0006
579 Alcohol dehydrogenase class 4 mu/sigma chain ADH7 0.0006
316 4-trimethylaminobutyraldehyde dehydrogenase ALDH9A1 0.0006
792 Aldehyde dehydrogenase, dimeric NADP-preferring ALDH3A1 0.0006
178 NADH-cytochrome b5 reductase 3 CYB5R3 0.0005
350 3-hydroxyacyl-CoA dehydrogenase type-2 HSD17B10 0.0005
812 Dihydrolipoyl dehydrogenase, mitochondrial DLD 0.0005
328 Sorbitol dehydrogenase SORD 0.0005
454 Peroxisomal multifunctional enzyme type 2 HSD17B4 0.0005
597 Dihydropteridine reductase QDPR 0.0005
363 NADP-dependent malic enzyme, mitochondrial ME3 0.0005
396 Alcohol dehydrogenase 4 ADH4 0.0005
857 Malate dehydrogenase, mitochondrial MDH2 0.0005
839 Short-chain specific acyl-CoA dehydrogenase, mitochondrial ACADS 0.0005
419 Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial HADH 0.0005
74 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial DLAT 0.0005
12 Alcohol dehydrogenase class 3 ADH5 0.0005
77 L-lactate dehydrogenase B chain LDHB 0.0005
607 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 NDUFA2 0.0005
374 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 NDUFB1 0.0005
247 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 NDUFA1 0.0005
343 NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial NDUFC1 0.0005
190 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4 NDUFA4 0.0005
755 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 NDUFA3 0.0005
353 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 NDUFA4L2 0.0005
236 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 NDUFA6 0.0005
272 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 NDUFB10 0.0005
313 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 NDUFB3 0.0005
300 NADH-ubiquinone oxidoreductase chain 4L MT-ND4L 0.0005
656 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 NDUFB9 0.0005
475 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial NDUFB2 0.0005
99 NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 NDUFS5 0.0005
30 NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial NDUFV3 0.0005
446 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 NDUFA7 0.0005
525 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 NDUFA5 0.0005
219 NADH-ubiquinone oxidoreductase chain 3 MT-ND3 0.0005
104 NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial NDUFS6 0.0005
417 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 NDUFB6 0.0005
324 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 NDUFB4 0.0005
568 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 NDUFB7 0.0005
598 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 NDUFA11 0.0005
582 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 NDUFA13 0.0005
829 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 NDUFA12 0.0005
609 15-hydroxyprostaglandin dehydrogenase [NAD+] HPGD 0.0005
602 Acyl carrier protein, mitochondrial NDUFAB1 0.0005
107 C-4 methylsterol oxidase SC4MOL 0.0005
216 Aldehyde dehydrogenase 3B2 ALDH3B2 0.0005
405 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 NDUFA8 0.0005
384 NADH-ubiquinone oxidoreductase chain 6 MT-ND6 0.0005
372 Estradiol 17-beta-dehydrogenase 3 HSD17B3 0.0005
555 NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial NDUFS4 0.0005
644 Heme oxygenase 2 HMOX2 0.0005
4982 Heme oxygenase 2 pbsA2 0.0005
746 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial NDUFB8 0.0005
326 L-lactate dehydrogenase A-like 6A LDHAL6A 0.0005
270 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial NDUFB5 0.0005
141 3-hydroxyisobutyrate dehydrogenase, mitochondrial HIBADH 0.0005
231 Glycerol-3-phosphate dehydrogenase [NAD+], cytoplasmic GPD1 0.0005
91 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial NDUFA10 0.0005
496 Aldehyde dehydrogenase 3B1 ALDH3B1 0.0005
50 Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating NSDHL 0.0005
41 NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial NDUFS8 0.0005
112 L-lactate dehydrogenase A-like 6B LDHAL6B 0.0005
671 Pyruvate dehydrogenase E1 component alpha subunit, testis-specific form, mitochondrial PDHA2 0.0005
628 Pyruvate dehydrogenase E1 component alpha subunit, somatic form, mitochondrial PDHA1 0.0005
848 Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial IDH3G 0.0005
152 NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial NDUFV2 0.0005
608 NADH-ubiquinone oxidoreductase chain 4 MT-ND4 0.0005
539 NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial NDUFV1 0.0005
662 Fatty aldehyde dehydrogenase ALDH3A2 0.0005
180 D-3-phosphoglycerate dehydrogenase PHGDH 0.0005
3726 D-3-phosphoglycerate dehydrogenase serA 0.0005
4291 D-3-phosphoglycerate dehydrogenase serA 0.0005
258 Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial ALDH6A1 0.0005
271 Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial ALDH4A1 0.0005
729 GDP-L-fucose synthetase TSTA3 0.0005
3463 GDP-L-fucose synthetase fcl 0.0005
487 Aldo-keto reductase family 1 member C4 AKR1C4 0.0005
167 L-lactate dehydrogenase C chain LDHC 0.0005
637 NADH-ubiquinone oxidoreductase chain 5 MT-ND5 0.0005
206 3-keto-steroid reductase HSD17B7 0.0005
196 D-beta-hydroxybutyrate dehydrogenase, mitochondrial BDH1 0.0005
721 NADH-ubiquinone oxidoreductase chain 2 MT-ND2 0.0005
14 Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial IDH3A 0.0005
335 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial NDUFA9 0.0005
616 Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial IDH3B 0.0005
9 Estradiol 17-beta-dehydrogenase 2 HSD17B2 0.0005
145 Corticosteroid 11-beta-dehydrogenase isozyme 2 HSD11B2 0.0005
643 Peroxisomal bifunctional enzyme EHHADH 0.0005
393 GDH/6PGL endoplasmic bifunctional protein [Includes: Glucose 1-dehydrogenase H6PD 0.0005
34 7-dehydrocholesterol reductase DHCR7 0.0005
711 UDP-glucose 6-dehydrogenase UGDH 0.0005
3672 UDP-glucose 6-dehydrogenase hasB 0.0005
149 Alpha-aminoadipic semialdehyde dehydrogenase ALDH7A1 0.0005
531 Aldehyde dehydrogenase X, mitochondrial ALDH1B1 0.0005
548 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial NDUFS1 0.0005
288 Trifunctional enzyme subunit alpha, mitochondrial HADHA 0.0005
599 Glyceraldehyde-3-phosphate dehydrogenase GAPDH 0.0005
4426 Glyceraldehyde-3-phosphate dehydrogenase gap 0.0005
4454 Glyceraldehyde-3-phosphate dehydrogenase gap 0.0005
4489 Glyceraldehyde-3-phosphate dehydrogenase gap 0.0005
794 Glyceraldehyde-3-phosphate dehydrogenase, testis-specific GAPDHS 0.0005
473 L-lactate dehydrogenase A chain LDHA 0.0005
166 NAD-dependent malic enzyme, mitochondrial ME2 0.0005
830 Glutamate dehydrogenase 2, mitochondrial GLUD2 0.0005
13 Aminomethyltransferase, mitochondrial AMT 0.0005
83 Alpha-aminoadipic semialdehyde synthase, mitochondrial AASS 0.0005
6026 Alcohol dehydrogenase 6 ADH6 0.0004
296 Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial MTHFD2 0.0004
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0004
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0004
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.0004
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.0004
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.0004
810 Heme oxygenase 1 HMOX1 0.0004
3391 Heme oxygenase 1 pbsA1 0.0004
248 Pyrroline-5-carboxylate reductase 1 PYCR1 0.0004
802 Pyrroline-5-carboxylate reductase 2 PYCR2 0.0004
251 Alcohol dehydrogenase 1A ADH1A 0.0004
626 Cysteine dioxygenase type 1 CDO1 0.0004
182 2-oxoglutarate dehydrogenase E1 component, mitochondrial OGDH 0.0004
611 Retinal dehydrogenase 1 ALDH1A1 0.0004
796 Inosine-5'-monophosphate dehydrogenase 2 IMPDH2 0.0004
640 Aldehyde dehydrogenase 1A3 ALDH1A3 0.0004
627 11-cis retinol dehydrogenase RDH5 0.0004
110 Pyruvate dehydrogenase E1 component subunit beta, mitochondrial PDHB 0.0004
66 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II HSD3B2 0.0004
569 Retinal dehydrogenase 2 ALDH1A2 0.0004
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0004
838 Inosine-5'-monophosphate dehydrogenase 1 IMPDH1 0.0004
714 Glutathione reductase, mitochondrial GSR 0.0004
57 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I HSD3B1 0.0004
380 Cytochrome P450 17A1 CYP17A1 0.0004
279 Tyrosinase TYR 0.0004
517 Alcohol dehydrogenase 1C ADH1C 0.0004
170 Succinate semialdehyde dehydrogenase, mitochondrial ALDH5A1 0.0004
147 Aldehyde dehydrogenase, mitochondrial ALDH2 0.0004
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0003
468 Cytochrome P450 4A11 CYP4A11 0.0003
3947 Xanthine dehydrogenase/oxidase XDH 0.0003