Pyrimethamine

Overview

Description
A medication used to treat and prevent infections caused by parasites such as malaria.
Description
A medication used to treat and prevent infections caused by parasites such as malaria.
DrugBank ID
DB00205
Type
Small Molecule
US Approved
YES
Other Approved
YES
Clinical Trials
Phase 0
1
Phase 1
31
Phase 2
31
Phase 3
72
Phase 4
37
Therapeutic Categories
  • Folic Acid Antagonists

Identification

Summary

Pyrimethamine is an antiparasitic drug used in the prevention and treatment of toxoplasmosis and malaria.

Brand Names
Daraprim
Generic Name
Pyrimethamine
DrugBank Accession Number
DB00205
Background

One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.

Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Structure
Weight
Average: 248.711
Monoisotopic: 248.082874143
Chemical Formula
C12H13ClN4
Synonyms
  • 2,4-Diamino-5-(4-chlorophenyl)-6-ethylpyrimidine
  • 2,4-Diamino-5-(P-chlorophenyl)-6-ethylpyrimidine
  • 2,4-Diamino-5-chlorophenyl-6-ethylpyrimidine
  • 5-(4-Chlorophenyl)-6-ethyl-2,4-diaminopyrimidine
  • 5-(4-Chlorophenyl)-6-ethyl-2,4-pyrimidinediamine
  • 5-(4'-Chlorophenyl)-2,4-diamino-6-ethylpyrimidine
  • CD
  • Chloridine
  • Chloridyn
  • Diaminopyritamin
  • Ethylpyrimidine
  • Pirimetamina
  • Primethamine
  • Pyriméthamine
  • Pyrimethamine
  • Pyrimethaminum
External IDs
  • NSC-3061
  • RP-4753
  • WR-2978

Pharmacology

Indication

For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatToxoplasmosis••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

Mechanism of action

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.

TargetActionsOrganism
ADihydrofolate reductase
inhibitor
Humans
AFolate receptor alpha
modulator
Humans
ABifunctional dihydrofolate reductase-thymidylate synthase
inhibitor
Plasmodium falciparum (isolate K1 / Thailand)
UBeta-hexosaminidase subunit betaNot AvailableHumans
Absorption

Well absorbed with peak levels occurring between 2 to 6 hours following administration

Volume of distribution

Not Available

Protein binding

87%

Metabolism

Hepatic

Route of elimination

Not Available

Half-life

96 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Pyrimethamine.
AcetazolamideThe therapeutic efficacy of Pyrimethamine can be increased when used in combination with Acetazolamide.
AcetophenazineThe risk or severity of QTc prolongation can be increased when Pyrimethamine is combined with Acetophenazine.
AcyclovirThe excretion of Acyclovir can be decreased when combined with Pyrimethamine.
AlimemazineThe risk or severity of QTc prolongation can be increased when Pyrimethamine is combined with Alimemazine.
Food Interactions
  • Administer folic acid supplement. Folic acid need is increased.
  • Take with food. Food reduces irritation.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pyrimethamine hydrochlorideFDZ9T27VWT19085-09-7JZCLIFPQURTYFA-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DaraprimTablet25 mg/1OralTILDE Sciences LLC1953-01-23Not applicableUS flag
DaraprimTablet25 mg/1OralPhysicians Total Care, Inc.1994-05-122011-06-30US flag
DaraprimTablet25 mg/1OralVyera Pharmaceuticals, LLC1953-01-23Not applicableUS flag
DaraprimTablet25 mgOralAmedra Pharmaceuticals LLC1952-12-312013-06-01Canada flag
DaraprimTablet25 mg/1OralGlaxosmithkline Inc1985-04-162013-03-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PyrimethamineTablet25 mg/1OralOAKRUM PHARMA, LLC2020-03-13Not applicableUS flag
PyrimethamineTablet25 mg/1OralTeva Pharmaceuticals USA, Inc.2021-12-15Not applicableUS flag
PyrimethamineTablet25 mg/1OralNorthStar Rx LLC2024-10-01Not applicableUS flag
PyrimethamineTablet25 mg/1OralDr. Reddy's Laboratories Limited2020-03-16Not applicableUS flag
PyrimethamineTablet25 mg/1OralFera Pharmaceuticals2021-10-07Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
FansidarPyrimethamine (25 mg/1) + Sulfadoxine (500 mg/1)TabletOralGenentech, Inc.1981-10-282012-04-18US flag
Fansidar TabletsPyrimethamine (25 mg) + Sulfadoxine (500 mg)TabletOralHoffmann La Roche1989-12-312000-07-27Canada flag
METAKELFINPyrimethamine (10 mg/mL) + Sulfametopyrazine (200 mg/mL)Solution / dropsOralPfizer Italia S.R.L.2014-07-082021-06-04Italy flag
METAKELFINPyrimethamine (25 mg) + Sulfametopyrazine (500 mg)TabletOralPfizer Italia S.R.L.2014-07-082021-06-04Italy flag
SULFADOXINA 500 MG + PIRIMETAMINA 25 MG TABLETASPyrimethamine (25 mg) + Sulfadoxine (500 mg)TabletOralCOLOMPACK S.A.2006-11-10Not applicableColombia flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Pyrimethamine LeucovorinPyrimethamine (50 mg/1) + Leucovorin calcium (20 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUS flag
Pyrimethamine LeucovorinPyrimethamine (12.5 mg/1) + Leucovorin calcium (2.5 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUS flag
Pyrimethamine LeucovorinPyrimethamine (25 mg/1) + Leucovorin calcium (5 mg/1)CapsuleOralSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding2015-11-25Not applicableUS flag
Pyrimethamine LeucovorinPyrimethamine (25 mg/1) + Leucovorin calcium (10 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUS flag
Pyrimethamine LeucovorinPyrimethamine (50 mg/1) + Leucovorin calcium (10 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUS flag

Categories

ATC Codes
P01BF09 — Artesunate, sulfadoxine and pyrimethamineP01BD01 — PyrimethamineP01BD51 — Pyrimethamine, combinationsP01BF04 — Artesunate, sulfalene and pyrimethamine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminopyrimidines and derivatives. These are organic compounds containing an amino group attached to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Aminopyrimidines and derivatives
Alternative Parents
Chlorobenzenes / Hydropyrimidines / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Chlorobenzene / Halobenzene / Heteroaromatic compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aminopyrimidine, monochlorobenzenes (CHEBI:8673)
Affected organisms
  • Plasmodium

Chemical Identifiers

UNII
Z3614QOX8W
CAS number
58-14-0
InChI Key
WKSAUQYGYAYLPV-UHFFFAOYSA-N
InChI
InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h3-6H,2H2,1H3,(H4,14,15,16,17)
IUPAC Name
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
SMILES
CCC1=C(C(N)=NC(N)=N1)C1=CC=C(Cl)C=C1

References

Synthesis Reference
US2576939
General References
  1. Gatton ML, Martin LB, Cheng Q: Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Jun;48(6):2116-23. [Article]
  2. Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y: Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem. 2004 Jan 15;47(2):345-54. [Article]
  3. FDA Approved Drug Products: DARAPRIM (pyrimethamine) tablets [Link]
Human Metabolome Database
HMDB0014350
KEGG Drug
D00488
KEGG Compound
C07391
PubChem Compound
4993
PubChem Substance
46505987
ChemSpider
4819
BindingDB
18512
RxNav
9010
ChEBI
8673
ChEMBL
CHEMBL36
ZINC
ZINC000000057464
Therapeutic Targets Database
DAP000633
PharmGKB
PA451193
PDBe Ligand
CP6
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pyrimethamine
PDB Entries
1j3j / 2bl9 / 2bla / 3qfx / 3qg2 / 3qgt / 3um5 / 4km0 / 6aog / 6nni
show 3 more
FDA label
Download (29.7 KB)
MSDS
Download (74 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableMalaria1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableMalaria caused by Plasmodium falciparum1somestatusstop reasonjust information to hide
Not AvailableCompletedEducational/Counseling/TrainingHuman Immunodeficiency Virus (HIV) Infections / Malaria caused by Plasmodium falciparum1somestatusstop reasonjust information to hide
Not AvailableCompletedHealth Services ResearchMalaria1somestatusstop reasonjust information to hide
Not AvailableCompletedOtherControlled Human Malaria Infection (CHMI) / Gametocytes / Malaria caused by Plasmodium falciparum / Transmission1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline llc
Packagers
  • DSM Corp.
  • GlaxoSmithKline Inc.
  • Kaiser Foundation Hospital
  • Medisca Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
TabletOral25 mg/1
TabletOral25.000 mg
TabletOral
Solution / dropsOral
SuspensionOral
TabletOral
CapsuleOral
SolutionOral
TabletOral25 mg
Prices
Unit descriptionCostUnit
Pyrimethamine powder8.88USD g
Daraprim 25 mg tablet0.98USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)233.5 °CPhysProp
water solubility121 mg/LNot Available
logP2.69HANSCH,C ET AL. (1995)
pKa7.34 (at 20 °C)PERRIN,DD (1972)
Predicted Properties
PropertyValueSource
Water Solubility0.179 mg/mLALOGPS
logP2.62ALOGPS
logP2.75Chemaxon
logS-3.1ALOGPS
pKa (Strongest Acidic)17.22Chemaxon
pKa (Strongest Basic)7.77Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area77.82 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity71.54 m3·mol-1Chemaxon
Polarizability25.79 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9973
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6217
P-glycoprotein substrateNon-substrate0.5822
P-glycoprotein inhibitor INon-inhibitor0.8643
P-glycoprotein inhibitor IINon-inhibitor0.9045
Renal organic cation transporterNon-inhibitor0.7451
CYP450 2C9 substrateNon-substrate0.8103
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6582
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.7586
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6667
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8016
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7833 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9337
hERG inhibition (predictor II)Non-inhibitor0.8586
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-01pk-0290000000-f67f41257c448ad0d840
GC-MS Spectrum - CI-BGC-MSsplash10-0002-0090000000-4e966bed391e234a23e3
Mass Spectrum (Electron Ionization)MSsplash10-0002-2590000000-6434b6f0181741b3ca41
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0090000000-a146b85d59fc9835ed4c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0090000000-84e4cea277c64351f21b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0190000000-d931593de00f33f04587
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0059-0980000000-a232e355dd50976aea07
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-005a-0920000000-7d48f7cfecbd7823803a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0290000000-b6d3f56ade24c0e6984c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0290000000-415b60a9caab352df184
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0032-2960000000-583d00b81182f34e5a94
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0090000000-29db06d81adc5b472831
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0090000000-ecbf85ab344f6b3af520
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000t-0290000000-b4f9833d2720969494d1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-7590000000-f3ae9b38c729192b0b1f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0fc0-0930000000-c694c146781663439e3b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9200000000-6e4dfaea573ffdcd7d31
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-157.5138945
predicted
DarkChem Lite v0.1.0
[M-H]-154.15897
predicted
DarkChem Lite v0.1.0
[M-H]-158.61043
predicted
DeepCCS 1.0 (2019)
[M+H]+156.6671945
predicted
DarkChem Lite v0.1.0
[M+H]+159.8297646
predicted
DarkChem Lite v0.1.0
[M+H]+160.98558
predicted
DeepCCS 1.0 (2019)
[M+Na]+157.9865945
predicted
DarkChem Lite v0.1.0
[M+Na]+170.2077157
predicted
DarkChem Lite v0.1.0
[M+Na]+167.06157
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details
1. Dihydrofolate reductase
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2
Specific Function
dihydrofolate reductase activity
Gene Name
DHFR
Uniprot ID
P00374
Uniprot Name
Dihydrofolate reductase
Molecular Weight
21452.61 Da
References
  1. Rastelli G, Pacchioni S, Parenti MD: Structure of Plasmodium vivax dihydrofolate reductase determined by homology modeling and molecular dynamics refinement. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3257-60. [Article]
  2. Fidock DA, Wellems TE: Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6. [Article]
  3. Wooden JM, Hartwell LH, Vasquez B, Sibley CH: Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum. Mol Biochem Parasitol. 1997 Mar;85(1):25-40. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Has high affinity for folate and folic acid analogs at neutral pH (PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release (PubMed:8567728). Required for normal embryonic development and normal cell proliferation (By similarity)
Specific Function
folic acid binding
Gene Name
FOLR1
Uniprot ID
P15328
Uniprot Name
Folate receptor alpha
Molecular Weight
29818.94 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Plasmodium falciparum (isolate K1 / Thailand)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Specific Function
dihydrofolate reductase activity
Gene Name
Not Available
Uniprot ID
P13922
Uniprot Name
Bifunctional dihydrofolate reductase-thymidylate synthase
Molecular Weight
71816.775 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Fohl LM, Roos DS: Fitness effects of DHFR-TS mutations associated with pyrimethamine resistance in apicomplexan parasites. Mol Microbiol. 2003 Nov;50(4):1319-27. [Article]
  4. McKie JH, Douglas KT, Chan C, Roser SA, Yates R, Read M, Hyde JE, Dascombe MJ, Yuthavong Y, Sirawaraporn W: Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria. J Med Chem. 1998 Apr 23;41(9):1367-70. [Article]
  5. Zolg JW, Plitt JR, Chen GX, Palmer S: Point mutations in the dihydrofolate reductase-thymidylate synthase gene as the molecular basis for pyrimethamine resistance in Plasmodium falciparum. Mol Biochem Parasitol. 1989 Oct;36(3):253-62. [Article]
  6. Zhang K, Rathod PK: Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science. 2002 Apr 19;296(5567):545-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides (PubMed:11707436, PubMed:8123671, PubMed:8672428, PubMed:9694901). The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide (PubMed:11707436). Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A (PubMed:8123671, PubMed:8672428, PubMed:9694901). During fertilization is responsible, at least in part, for the zona block to polyspermy. Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and inactivates the sperm galactosyltransferase-binding site, accounting for the block in sperm binding to the zona pellucida (By similarity)
Specific Function
acetylglucosaminyltransferase activity
Gene Name
HEXB
Uniprot ID
P07686
Uniprot Name
Beta-hexosaminidase subunit beta
Molecular Weight
63136.825 Da
References
  1. Bateman KS, Cherney MM, Mahuran DJ, Tropak M, James MN: Crystal structure of beta-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone. J Med Chem. 2011 Mar 10;54(5):1421-9. doi: 10.1021/jm101443u. Epub 2011 Jan 25. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
antiporter activity
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Oh J, Chung H, Park SI, Yi SJ, Jang K, Kim AH, Yoon J, Cho JY, Yoon SH, Jang IJ, Yu KS, Chung JY: Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans. Diabetes Obes Metab. 2016 Jan;18(1):104-8. doi: 10.1111/dom.12577. Epub 2015 Oct 26. [Article]
  2. Kusuhara H, Ito S, Kumagai Y, Jiang M, Shiroshita T, Moriyama Y, Inoue K, Yuasa H, Sugiyama Y: Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects. Clin Pharmacol Ther. 2011 Jun;89(6):837-44. doi: 10.1038/clpt.2011.36. Epub 2011 May 4. [Article]
  3. May M, Schindler C: Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83. doi: 10.1177/2042018816638050. Epub 2016 Mar 31. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Specific Function
antiporter activity
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Oh J, Chung H, Park SI, Yi SJ, Jang K, Kim AH, Yoon J, Cho JY, Yoon SH, Jang IJ, Yu KS, Chung JY: Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans. Diabetes Obes Metab. 2016 Jan;18(1):104-8. doi: 10.1111/dom.12577. Epub 2015 Oct 26. [Article]
  2. Kusuhara H, Ito S, Kumagai Y, Jiang M, Shiroshita T, Moriyama Y, Inoue K, Yuasa H, Sugiyama Y: Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects. Clin Pharmacol Ther. 2011 Jun;89(6):837-44. doi: 10.1038/clpt.2011.36. Epub 2011 May 4. [Article]
  3. May M, Schindler C: Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83. doi: 10.1177/2042018816638050. Epub 2016 Mar 31. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 09, 2024 06:17