DT-Web

DB08878 - Aminopterin


Identification
Name Aminopterin
Accession Number DB08878
Type small molecule
Description Aminopterin is an amino derivative of folic acid, which was once used as an antineoplastic agent in the treatment of pediatric leukemia. In the 1950's its production was discontinued in favor of methotrexate, which is less potent but less toxic. Off label, aminopterin has also been used in the treatment of psoriasis. Clinicians need to be aware of the characteristic teratologic effects of aminopterin and methotrexate.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 440.4127
Groups withdrawn
Monoisotopic Weight 440.15566579
Pharmacology
Indication Prior to its withdrawal, aminopterin was initially used in the treatment of childhood leukemia; specifically to induce remissions. Later, aminopterin was used off-label in the United States to treat psoriasis, yielding dramatic lesion clearing. Aminopterin was later supplanted by methotrexate for treating cancer because of its better therapeutic index. Aminopterin (as well as methotrexate) has also been explored for use as an abortifacient. However, their association with severe congenital malformations and teratogenic effects have become known as fetal aminopterin syndrome.
Mechanism of action Aminopterin is an amino derivative of folic acid which binds competitively to the dihydrofolate reductase enzyme to block tetrahydrofolate synthesis. Tetrahydrofolate is essential in the production of purines and pyrimadines, thus it's deficiency results in a reduction of DNA, RNA and protein synthesis.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Enzymes


Dihydrofolate reductase
Name Dihydrofolate reductase
Gene Name DHFR
Actions inhibitor
References
  • Cocco L, Groff JP, Temple C Jr, Montgomery JA, London RE, Matwiyoff NA, Blakley RL: Carbon-13 nuclear magnetic resonance study of protonation of methotrexate and aminopterin bound to dihydrofolate reductase. Biochemistry. 1981 Jul 7;20(14):3972-8. - Pubmed
DTHybrid score 1.1661

Transporters


Heme carrier protein 1
Name Heme carrier protein 1
Gene Name SLC46A1
Actions Not Available
References
  • Menter A, Thrash B, Cherian C, Matherly LH, Wang L, Gangjee A, Morgan JR, Maeda DY, Schuler AD, Kahn SJ, Zebala JA: Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis is stereoselective: evidence for a mechanism involving the proton-coupled folate transporter. J Pharmacol Exp Ther. 2012 Sep;342(3):696-708. doi: 10.1124/jpet.112.195479. Epub 2012 May 31. - Pubmed
DTHybrid score 0.3436

Predictions


Id Partner name Gene Name Score
2381 Dihydrofolate reductase DFR1 1.1661
2833 Dihydrofolate reductase Not Available 1.1661
2931 Dihydrofolate reductase folA 1.1661
3544 Dihydrofolate reductase folA 1.1661
3682 Dihydrofolate reductase folA 1.1661
6642 Dihydrofolate reductase folA 1.1661
6756 Dihydrofolate reductase dfrA 1.1661
6236 Trimethoprim-sensitive dihydrofolate reductase dfrB 0.0961
293 Gamma-glutamyl hydrolase GGH 0.0533
718 Folate receptor gamma FOLR3 0.0418
299 Folate receptor beta FOLR2 0.0418
804 Mitochondrial folate transporter/carrier SLC25A32 0.0418
24 Thymidylate synthase TMP1 0.0415
359 Thymidylate synthase TYMS 0.0415
2626 Thymidylate synthase thyA 0.0415
2729 Thymidylate synthase thyA 0.0415
5352 Thymidylate synthase THYA 0.0415
1124 Sepiapterin reductase SPR 0.0413
78 Acetyl-CoA acetyltransferase, mitochondrial ACAT1 0.037
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0346
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.034
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0327
3917 Methylenetetrahydrofolate reductase MTHFR 0.0312
2038 Inhibitor of nuclear factor kappa-B kinase subunit beta IKBKB 0.0249
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0237
33 Cystine/glutamate transporter SLC7A11 0.0232
2164 Multidrug resistance-associated protein 4 ABCC4 0.022
2287 Bifunctional purine biosynthesis protein PURH [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase ATIC 0.0219
275 Arachidonate 5-lipoxygenase ALOX5 0.0204
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0201
620 Bifunctional dihydrofolate reductase-thymidylate synthase Not Available 0.02
5818 Folate receptor alpha FOLR1 0.0195
1729 Solute carrier family 22 member 6 SLC22A6 0.0176
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0171
6013 Cytochrome P450 2E1 CYP2E1 0.0153
290 Prostaglandin G/H synthase 2 PTGS2 0.0146
20 Prostaglandin G/H synthase 1 PTGS1 0.0136
1043 Trifunctional purine biosynthetic protein adenosine-3 [Includes: Phosphoribosylamine--glycine ligase GART 0.0128
4757 Cytochrome P450 2C9 CYP2C9 0.0123
4118 Cytochrome P450 3A5 CYP3A5 0.0118
4924 Cytochrome P450 2C8 CYP2C8 0.01
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0098
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0098
6150 Solute carrier organic anion transporter family member 4C1 SLCO4C1 0.0095
6020 Aldehyde oxidase AOX1 0.0093
1588 Multidrug resistance protein 1 ABCB1 0.009
6148 Multidrug resistance-associated protein 7 ABCC10 0.0085
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0085
738 Monocarboxylate transporter 1 SLC16A1 0.0084
4773 Deoxycytidine kinase DCK 0.0081
4119 Cytochrome P450 2D6 CYP2D6 0.008
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.008
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0077
1024 Solute carrier family 22 member 11 SLC22A11 0.0072
6143 Solute carrier family 22 member 7 SLC22A7 0.0071
862 Multidrug resistance-associated protein 1 ABCC1 0.0066
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0066
4512 Cytochrome P450 3A4 CYP3A4 0.0065
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0065
6142 Solute carrier family 22 member 8 SLC22A8 0.0063
587 Serum albumin ALB 0.0057
6016 Cytochrome P450 2C19 CYP2C19 0.0033
4200 Cytochrome P450 1A2 CYP1A2 0.0032
646 Malate dehydrogenase, cytoplasmic MDH1 0.0019
635 Estradiol 17-beta-dehydrogenase 8 HSD17B8 0.0019
666 NADP-dependent malic enzyme ME1 0.0019
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
4484 2,5-diketo-D-gluconic acid reductase A dkgA 0.0017
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0016
679 C-1-tetrahydrofolate synthase, cytoplasmic MTHFD1 0.0016
686 Aldo-keto reductase family 1 member C2 AKR1C2 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
139 Aldo-keto reductase family 1 member C1 AKR1C1 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
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
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
822 Aldose reductase AKR1B1 0.0013
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0012
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0012
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
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