Levoleucovorin

Identification

Name
Levoleucovorin
Accession Number
DB11596
Description

Levoleucovorin is the enantiomerically active form of Folinic Acid (also known as 5-formyl tetrahydrofolic acid or leucovorin). Commercially available leucovorin is composed of a 1:1 racemic mixture of the dextrorotary and levorotary isomers, while levoleucovorin contains only the pharmacologically active levo-isomer. In vitro, the levo-isomer has been shown to be rapidly converted to the biologically available methyl-tetrahydrofolate form while the dextro form is slowly excreted by the kidneys. Despite this difference in activity, the two commercially available forms have been shown to be pharmacokinetically identical and may be used interchangeably with limited differences in efficacy or side effects (Kovoor et al, 2009).

As folate analogs, levoleucovorin and leucovorin are both used to counteract the toxic effects of folic acid antagonists, such as methotrexate, which act by inhibiting the enzyme dihydrofolate reductase (DHFR). They are indicated for use as rescue therapy following use of high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Levoleucovorin, as the product Fusilev (FDA), has an additional indication for use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer.

Folic acid is an essential B vitamin required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. However, in order to function in this role, it must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted when high-dose methotrexate is used for cancer therapy. As methotrexate functions as a DHFR inhibitor to prevent DNA synthesis in rapidly dividing cells, it also prevents the formation of DHF and THF. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects of methotrexate therapy. As levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF), they are able to bypass DHFR reduction and act as a cellular replacement for the co-factor THF, thereby preventing these toxic side effects.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 473.4393
Monoisotopic: 473.165896125
Chemical Formula
C20H23N7O7
Synonyms
  • (6S)-5-Formyl-5,6,7,8-tetrahydrofolic acid
  • (6S)-5-formyltetrahydrofolic acid
  • (6S)-Folinic acid
  • (6S)-Leucovorin
  • (S)-Leucovorin
  • ácido levofolínico
  • Citrovorum factor
  • L-Folinic acid
  • Levofolene
  • Levofolinic acid
  • N-[4-({[(6S)-2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamic acid
External IDs
  • LFP 754
  • LFP-754
  • LFP754

Pharmacology

Indication

Levoleucovorin is indicated for use as rescue therapy following high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Levoleucovorin, as the product Fusilev (FDA, dosed at one-half the usual dose of racemic d,l-leucovorin), has an additional indication for use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer (although they should not be mixed in the same infusion as a precipitate may form).

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Levoleucovorin is actively and passively transported across cell membranes. In vivo, levoleucovorin is converted to 5-methyltetrahydrofolic acid (5-methyl-THF), the primary circulating form of active reduced folate. Levoleucovorin and 5-methyl-THF are polyglutamated intracellularly by the enzyme folylpolyglutamate synthetase. Folylpolyglutamates are active and participate in biochemical pathways that require reduced folate.

Mechanism of action

Folic acid is an essential B vitamin required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. However, in order to function in this role, it must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted when high-dose methotrexate is used for cancer therapy. As methotrexate functions as a DHFR inhibitor to prevent DNA synthesis in rapidly dividing cells, it also prevents the formation of DHF and THF. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects of methotrexate therapy. As levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF), they are able to bypass DHFR reduction and act as a cellular replacement for the co-factor THF, thereby preventing these toxic side effects.

TargetActionsOrganism
USerine hydroxymethyltransferaseNot AvailableShigella flexneri
Absorption

After rapid intravenous administration, serum total tetrahydrofolate (total-THF) concentrations reached a mean peak of 1722 ng/mL. Serum (6S)-5-methyl-5,6,7,8-tetrahydrofolate concentrations reached a mean peak of 275 ng/mL and the mean time to peak was 0.9 hours.

Volume of distribution

Data can't be found.

Protein binding

Does not bind human serum albumin.

Metabolism

Extensively converted to tetrahydrofolic derivatives.

Hover over products below to view reaction partners

Route of elimination

Urinary.

Half-life

The mean terminal half-life for total-THF and (6S)-5-methyl-5,6,7,8-tetrahydrofolate was 5.1 and 6.8 hours, respectively.

Clearance

Data can't be found.

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

ِAcute intravenous LD50 values in adult mice and rats were 575 mg/kg (1725 mg/m²) and 378 mg/kg ( 2268 mg/m²), respectively.

Affected organisms
  • Humans and other mammals
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
CapecitabineThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Capecitabine.
CarbamazepineThe serum concentration of Carbamazepine can be decreased when it is combined with Levoleucovorin.
ColestipolThe serum concentration of Levoleucovorin can be decreased when it is combined with Colestipol.
CycloguanilThe therapeutic efficacy of Cycloguanil can be decreased when used in combination with Levoleucovorin.
DapsoneThe therapeutic efficacy of Dapsone can be decreased when used in combination with Levoleucovorin.
FlucytosineThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Flucytosine.
FluorouracilThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Fluorouracil.
FosphenytoinThe serum concentration of Fosphenytoin can be decreased when it is combined with Levoleucovorin.
GlucarpidaseThe serum concentration of the active metabolites of Levoleucovorin can be reduced when Levoleucovorin is used in combination with Glucarpidase resulting in a loss in efficacy.
MethotrexateThe therapeutic efficacy of Methotrexate can be decreased when used in combination with Levoleucovorin.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity
    Available for Purchase

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level
    Available for Purchase

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
No interactions found.

Products

Purchasing individual compounds or compound libraries for your research?
Learn More
Product Ingredients
IngredientUNIICASInChI Key
Levoleucovorin calcium778XL6VBS880433-71-2KVUAALJSMIVURS-QNTKWALQSA-L
Levoleucovorin calcium pentahydrateWA16A5Y52X419573-16-3NPPBLUASYYNAIG-BWDMFOMUSA-L
Levoleucovorin disodium5TXQ76K65T1141892-29-6FSDMNNPYPVJNAT-NJHZPMQHSA-L
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FusilevInjection, powder, lyophilized, for solution50 mg/5mLIntravenousAcrotech Biopharma Llc2008-08-15Not applicableUS flag
FusilevInjection, powder, lyophilized, for solution50 mg/5mLIntravenousSpectrum Pharmaceuticals, Inc.2008-08-152019-02-28US flag
FusilevInjection, solution10 mg/1mLIntravenousAcrotech Biopharma Llc2011-09-15Not applicableUS flag
FusilevInjection, powder, lyophilized, for solution50 mg/5mLIntravenousCangene Bio Pharma2008-08-152010-02-24US flag
FusilevInjection, solution10 mg/1mLIntravenousAcrotech Biopharma Llc2011-09-15Not applicableUS flag
FusilevInjection, solution10 mg/1mLIntravenousSpectrum Pharmaceuticals, Inc.2011-09-152019-02-28US flag
KhapzoryInjection, powder, lyophilized, for solution300 mg/6mLIntravenousAcrotech Biopharma Llc2019-01-02Not applicableUS flag
KhapzoryInjection, powder, lyophilized, for solution300 mg/6mLIntravenousSpectrum Pharmaceuticals, Inc.2019-01-02Not applicableUS flag
KhapzoryInjection, powder, lyophilized, for solution175 mg/3.5mLIntravenousAcrotech Biopharma Llc2019-01-02Not applicableUS flag
KhapzoryInjection, powder, lyophilized, for solution175 mg/3.5mLIntravenousSpectrum Pharmaceuticals, Inc.2019-01-02Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LevoleucovorinInjection, powder, lyophilized, for solution50 mg/1IntravenousAmneal Pharmaceuticals LLC2017-02-13Not applicableUS flag
LevoleucovorinInjection, solution10 mg/1mLIntravenousIngenus Pharmaceuticals, LLC2018-05-08Not applicableUS flag
LevoleucovorinInjection10 mg/1mLIntravenousFosun Pharma USA Inc.2019-06-25Not applicableUS flag
LevoleucovorinInjection, solution175 mg/17.5mLIntravenousDr.Reddy's Laboratories Inc2018-09-26Not applicableUS flag
LevoleucovorinInjection, solution175 mg/17.5mLIntravenousSandoz Inc2015-04-23Not applicableUS flag
LevoleucovorinInjection, solution250 mg/25mLIntravenousNorthstar RxLLC2018-09-26Not applicableUS flag
LevoleucovorinInjection, powder, lyophilized, for solution50 mg/5mLIntravenousWest-Ward Pharmaceuticals Corp2016-07-07Not applicableUS flag
LevoleucovorinInjection, solution10 mg/1mLIntravenousMeitheal Pharmaceuticals Inc.2019-08-16Not applicableUS flag
LevoleucovorinInjection10 mg/1mLIntravenousGland Pharma Limited2018-09-20Not applicableUS flag
LevoleucovorinInjection, powder, lyophilized, for solution10 mg/1mLIntravenousActavis Pharma, Inc.2017-02-14Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Biopar delta-FORTELevoleucovorin (2.5 mg/1) + Cobalamin (50 ug/1) + Cobamamide (50 ug/1) + Dihydrofolic Acid (1 mg/1) + Gastric intrinsic factor (50 mg/1) + Levomefolate magnesium (7 mg/1)CapsuleOralJaymac Pharmacueticals LLC2020-09-01Not applicableUS flag

Categories

ATC Codes
V03AF10 — Sodium levofolinateV03AF04 — Calcium levofolinate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pteridines and derivatives
Sub Class
Pterins and derivatives
Direct Parent
Tetrahydrofolic acids
Alternative Parents
Glutamic acid and derivatives / Hippuric acids / N-acyl-alpha amino acids / Aminobenzamides / Aniline and substituted anilines / Benzoyl derivatives / Phenylalkylamines / Secondary alkylarylamines / Aminopyrimidines and derivatives / Pyrimidones
show 13 more
Substituents
Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Aminobenzamide / Aminobenzoic acid or derivatives / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
5-formyltetrahydrofolic acid (CHEBI:63606)

Chemical Identifiers

UNII
990S25980Y
CAS number
68538-85-2
InChI Key
VVIAGPKUTFNRDU-STQMWFEESA-N
InChI
InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32)/t12-,13-/m0/s1
IUPAC Name
(2S)-2-{[4-({[(6S)-2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
SMILES
NC1=NC(=O)C2=C(NC[[email protected]](CNC3=CC=C(C=C3)C(=O)N[[email protected]@H](CCC(O)=O)C(O)=O)N2C=O)N1

References

General References
  1. Kovoor PA, Karim SM, Marshall JL: Is levoleucovorin an alternative to racemic leucovorin? A literature review. Clin Colorectal Cancer. 2009 Oct;8(4):200-6. doi: 10.3816/CCC.2009.n.034. [PubMed:19822510]
  2. Allegra CJ, Chabner BA, Drake JC, Lutz R, Rodbard D, Jolivet J: Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J Biol Chem. 1985 Aug 15;260(17):9720-6. [PubMed:2410416]
  3. Stover PJ, Field MS: Trafficking of intracellular folates. Adv Nutr. 2011 Jul;2(4):325-31. doi: 10.3945/an.111.000596. Epub 2011 Jun 28. [PubMed:22332074]
  4. Chuang VT, Suno M: Levoleucovorin as replacement for leucovorin in cancer treatment. Ann Pharmacother. 2012 Oct;46(10):1349-57. doi: 10.1345/aph.1Q677. Epub 2012 Oct 2. [PubMed:23032661]
  5. Zittoun J: Pharmacokinetics and in vitro studies of l-leucovorin. Comparison with the d and d,l-leucovorin. Ann Oncol. 1993;4 Suppl 2:1-5. [PubMed:8353099]
  6. Schilsky RL, Ratain MJ: Clinical pharmacokinetics of high-dose leucovorin calcium after intravenous and oral administration. J Natl Cancer Inst. 1990 Sep 5;82(17):1411-5. [PubMed:2388292]
  7. product info [Link]
  8. product info [Link]
KEGG Drug
D04715
PubChem Compound
149436
PubChem Substance
347828002
ChemSpider
131714
BindingDB
286
RxNav
877015
ChEBI
63606
ChEMBL
CHEMBL1908841
ZINC
ZINC000009212427
PharmGKB
PA450198
PDBe Ligand
FFO
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Levoleucovorin
PDB Entries
1dfo / 1eqb / 1jol / 1jom / 1pj7 / 1wop / 2vmy / 3sd3 / 3suh / 3uwl
show 7 more
FDA label
Download (5.52 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Undifferentiated Leukemia (AUL) / Childhood T Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Lymphoblastic Lymphoma / Ann Arbor Stage I B Lymphoblastic Lymphoma / Ann Arbor Stage II B Lymphoblastic Lymphoma / Childhood B Acute Lymphoblastic Leukemia / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Childhood B Lymphoblastic Lymphoma / Down Syndrome (DS) / Hypodiploid B Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive1
3Active Not RecruitingTreatmentAdult T Acute Lymphoblastic Leukemia / Ann Arbor Stage II Adult Lymphoblastic Lymphoma / Ann Arbor Stage II Childhood Lymphoblastic Lymphoma / Ann Arbor Stage III Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Childhood Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult Lymphoblastic Lymphoma / Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma / Childhood T Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentB Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Ph-Like Acute Lymphoblastic Leukemia / Testicular Leukemia1
3Active Not RecruitingTreatmentChildhood Atypical Teratoid/Rhabdoid Tumor1
3Active Not RecruitingTreatmentChoriocarcinoma / FIGO Stage I Gestational Trophoblastic Tumor / FIGO Stage II Gestational Trophoblastic Tumor / FIGO Stage III Gestational Trophoblastic Tumor / Hydatidiform Mole1
3Active Not RecruitingTreatmentColon Mucinous Adenocarcinoma / Colon Signet Ring Cell Adenocarcinoma / Lynch Syndrome / Stage IIA Colon Cancer AJCC v7 / Stage IIB Colon Cancer AJCC v7 / Stage IIC Colon Cancer AJCC v71
3Active Not RecruitingTreatmentRecurrent B Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentT Acute Lymphoblastic Leukemia / T Lymphoblastic Lymphoma1
3CompletedTreatmentColon Adenocarcinoma / Stage IIA Colon Cancer AJCC v7 / Stage IIB Colon Cancer AJCC v7 / Stage IIC Colon Cancer AJCC v7 / Stage IIIA Colon Cancer AJCC v7 / Stage IIIB Colon Cancer AJCC v7 / Stage IIIC Colon Cancer AJCC v71

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
Injection, powder, for solution25 MG
Injection, solution10 MG/ML
Powder, for solutionParenteral100 MG
Powder, for solutionParenteral175 MG
Injection, powder, lyophilized, for solutionIntravenous50 mg/5mL
Injection, powder, lyophilized, for solutionIntravenous175 mg/3.5mL
Injection, powder, lyophilized, for solutionIntravenous300 mg/6mL
Granule, for solutionOral2.5 MG
Granule, for solutionOral5 mg
Injection, powder, for solution1.5 MG/3ML
Injection, powder, for solutionIntravenous25 MG
Injection, powder, lyophilized, for solutionIntravenous1.5 mg
Injection, solutionIntramuscular1.5 MG/1ML
Injection, powder, for solutionParenteral100 MG
Injection, powder, for solutionParenteral25 MG
Injection, powder, for solutionParenteral7.5 MG/1ML
SolutionOral7.5 MG/10ML
Tablet15 MG
Tablet4 MG
Tablet7.5 MG
InjectionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/1
Injection, solutionIntravenous175 mg/17.5mL
Injection, solutionIntravenous250 mg/25mL
Injection, solutionIntravenous10 mg/1mL
Injection, solutionParenteral50 MG/ML
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6500829No2002-12-312022-03-07US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.3 mg/mLALOGPS
logP-1.1ALOGPS
logP-2.8ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.27ChemAxon
pKa (Strongest Basic)2.69ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area215.55 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.46 m3·mol-1ChemAxon
Polarizability44.58 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Shigella flexneri
Pharmacological action
Unknown
Curator comments
Levoleucovorin, a pharmacologically active levo-isomer of racemic leucovirin, has been shown to be an inhibitor of this enzyme in vitro. However, clinically, it is not used for this purpose.
General Function
Pyridoxal phosphate binding
Specific Function
Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required ...
Gene Name
glyA
Uniprot ID
P0A827
Uniprot Name
Serine hydroxymethyltransferase
Molecular Weight
45316.33 Da
References
  1. Schirch V, Szebenyi DM: Serine hydroxymethyltransferase revisited. Curr Opin Chem Biol. 2005 Oct;9(5):482-7. doi: 10.1016/j.cbpa.2005.08.017. [PubMed:16125438]
  2. Chang WN, Tsai JN, Chen BH, Huang HS, Fu TF: Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2127-37. doi: 10.1124/dmd.107.016840. Epub 2007 Jul 30. [PubMed:17664250]
  3. Stover P, Schirch V: 5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase. J Biol Chem. 1991 Jan 25;266(3):1543-50. [PubMed:1988436]
  4. Pai VR, Rajaram V, Bisht S, Bhavani BS, Rao NA, Murthy MR, Savithri HS: Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyltransferase: the role of Asn(341), Tyr(60) and Phe(351) in tetrahydrofolate binding. Biochem J. 2009 Mar 15;418(3):635-42. doi: 10.1042/BJ20081739. [PubMed:19046138]
  5. Paiardini A, Fiascarelli A, Rinaldo S, Daidone F, Giardina G, Koes DR, Parroni A, Montini G, Marani M, Paone A, McDermott LA, Contestabile R, Cutruzzola F: Screening and in vitro testing of antifolate inhibitors of human cytosolic serine hydroxymethyltransferase. ChemMedChem. 2015 Mar;10(3):490-7. doi: 10.1002/cmdc.201500028. Epub 2015 Feb 10. [PubMed:25677305]

Drug created on May 19, 2016 13:51 / Updated on November 25, 2020 14:42

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates