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Leucovorin Calcium

PubChem CID
135403647
Structure
Leucovorin Calcium_small.png
Leucovorin Calcium_3D_Structure.png
Molecular Formula
Synonyms
  • calcium folinate
  • LEUCOVORIN CALCIUM
  • 1492-18-8
  • Folinic acid calcium salt
  • Calcium leucovorin
Molecular Weight
511.5 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2019-01-15
  • Modify:
    2025-01-18
Description
Leucovorin Calcium is an active metabolite of folic acid (also called folinic acid and citrovorum factor), which does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonist-type chemotherapeutic drugs. Leucovorin calcium counteracts the toxic effects of these medications, 'rescuing' the patient while permitting the antitumor activity of the folate antagonist. This agent also potentiates the effects of fluorouracil and its derivatives by stabilizing the binding of the drug's metabolite to its target enzyme, thus prolonging drug activity. (NCI04)
Levoleucovorin Calcium is a levo isoform of leucovorin calcium with antineoplastic activity. Levoleucovorin is an active metabolite of folic acid, which does not require metabolism by dihydrofolate reductase. This agent counteracts the toxic effects of other folic acid derivative agents, rescuing the patient while permitting the antitumor activity of the folate antagonist. This agent also potentiates the effects of fluorouracil and its derivatives by stabilizing the binding of the drug's metabolite to its target enzyme, thus prolonging drug activity.
See also: Leucovorin (has active moiety); Leucovorin calcium; pyrimethamine (component of).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Leucovorin Calcium.png

1.2 3D Conformer

3D Conformer of Parent

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

calcium;(2S)-2-[[4-[(2-amino-5-formyl-4-oxo-3,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C20H23N7O7.Ca/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);/q;+2/p-2/t12?,13-;/m0./s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

KVUAALJSMIVURS-ZEDZUCNESA-L
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C1C(N(C2=C(N1)N=C(NC2=O)N)C=O)CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)[O-])C(=O)[O-].[Ca+2]
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C20H21CaN7O7
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

1492-18-8
6035-45-6
80433-71-2

2.3.3 Deprecated CAS

1236362-90-5, 30771-29-0, 6035-86-5, 6209-45-6

2.3.4 European Community (EC) Number

2.3.5 UNII

2.3.6 ChEBI ID

2.3.7 ChEMBL ID

2.3.8 DSSTox Substance ID

2.3.9 KEGG ID

2.3.10 NCI Thesaurus Code

2.3.11 RXCUI

2.3.12 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 5 Formyltetrahydrofolate
  • 5 Formyltetrahydropteroylglutamate
  • 5-Formyltetrahydrofolate
  • 5-Formyltetrahydropteroylglutamate
  • Acid, Folinic
  • Calcium Folinate
  • Calcium Leucovorin
  • Citrovorum Factor
  • Factor, Citrovorum
  • Folinate, Calcium
  • Folinic Acid
  • Folinic Acid SF
  • Folinic Acid-SF
  • Leucovorin
  • Leucovorin, (D)-Isomer
  • Leucovorin, (DL)-Isomer
  • Leucovorin, (R)-Isomer
  • Leucovorin, Calcium
  • Leucovorin, Calcium (1:1) Salt
  • Leucovorin, Calcium (1:1) Salt, (DL)-Isomer
  • Leucovorin, Calcium (1:1) Salt, Pentahydrate
  • Leucovorin, Monosodium Salt
  • Leukovorin
  • Leukovorum
  • Monosodium Salt Leucovorin
  • N(5)-Formyltetrahydrofolate
  • Wellcovorin

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
511.5 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
10
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
7
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
511.1128369 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
511.1128369 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
221 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
35
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
900
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
2
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Solubility

DMSO « 1 (mg/mL)
H2O 100 (mg/mL)
0.1 N NaOH < 20 (mg/mL)

3.2.2 Stability / Shelf Life

Stability
Bulk: Calcium leucovorin was stable in bulk form after 4 weeks storage at 60 ° C (HPLC). Solution: Leucovorin in 0.1 N NaOH (pH 13) and in deionized water (pH6) was stable at room temperature under laboratory illumination for at least 24 hours (HPLC).

3.2.3 Optical Rotation

(c = 1, H2O) [a]20 D = 13.0 ± 2º

3.2.4 Collision Cross Section

202.35 Ų [M-H]- [CCS Type: DT; Method: stepped-field]

198.8 Ų [M+H]+ [CCS Type: DT; Method: stepped-field]

3.3 Chemical Classes

3.3.1 Drugs

3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Antidotes; Vitamin B Complex; Vitamins
Human drug -> Prescription; Discontinued; Active ingredient (LEUCOVORIN CALCIUM)
Human drug -> Discontinued
Human drug -> Prescription; Discontinued
Human drug -> Prescription; Discontinued; Active ingredient (LEVOLEUCOVORIN CALCIUM)

4 Spectral Information

4.1 UV Spectra

(0.1 N NaOH) max=282 ± 2 nm E = 23,000 - 26,500

4.2 Chromatograms

4.2.1 HPLC

HPLC
Column: 30 cm x 4 mm i.d. Spherisorb ODS Mobile Phase: 15% McOH in 0.1 M KH pH adjusted to 4.0 Flow Rate: 1.5 mL /min Detection: UV at 254 nm Sample Preparation: 1 mg/mL in water or internal standard solution Internal Standard: Folic acid (1 mg/mL in 0.02 N NaOH) Retention Volume: 12.0 mL (NSC -3590) 20.2 mL (I.S.)

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Antidotes; Vitamin B Complex; Vitamins

7.3 FDA Approved Drugs

7.4 FDA Orange Book

7.5 FDA National Drug Code Directory

7.6 Drug Labels

Drug and label
Active ingredient and drug
Drug and label
Active ingredient and drug

7.7 Cancer Drugs

Drug Name
Leucovorin Calcium
FDA Approved
Yes
Drug Use

Leucovorin calcium is approved to be used alone or with other drugs to treat:

• Colorectal cancer. It is used with fluorouracil as palliative treatment in patients with advanced disease.

• Anemia. It is used to treat megaloblastic anemia that occurs when the body does not get enough of a vitamin called folic acid. It is used by patients who cannot take the vitamin by mouth.

Leucovorin calcium is also used to prevent and treat the toxic effects of high-dosemethotrexate when used to treat osteosarcoma and other types of cancer. It is also used to treat overdoses of methotrexate or other folic acid antagonists. The drug is also being studied in the treatment of other conditions and types of cancer.

7.8 Clinical Trials

7.8.1 ClinicalTrials.gov

7.8.2 EU Clinical Trials Register

7.8.3 NIPH Clinical Trials Search of Japan

8 Pharmacology and Biochemistry

8.1 MeSH Pharmacological Classification

Antidotes
Agents counteracting or neutralizing the action of POISONS. (See all compounds classified as Antidotes.)
Vitamin B Complex
A group of water-soluble vitamins, some of which are COENZYMES. (See all compounds classified as Vitamin B Complex.)

8.2 FDA Pharmacological Classification

1 of 2
Non-Proprietary Name
LEUCOVORIN CALCIUM
Pharmacological Classes
Folic Acid [CS]; Folate Analog [EPC]
2 of 2
Non-Proprietary Name
LEVOLEUCOVORIN CALCIUM
Pharmacological Classes
Folate Analog [EPC]; Folic Acid [CS]

8.3 ATC Code

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

V - Various

V03 - All other therapeutic products

V03A - All other therapeutic products

V03AF - Detoxifying agents for antineoplastic treatment

V03AF03 - Calcium folinate

9 Use and Manufacturing

9.1 Uses

Use (kg; approx.) in Germany (2009): >250

Consumption (g per capita; approx.) in Germany (2009): 0.00305

Calculated removal (%): 22

9.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

1 of 3
View All
Note
Pictograms displayed are for 96.2% (50 of 52) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 3.8% (2 of 52) of reports.
Pictogram(s)
Irritant
Health Hazard
Signal
Danger
GHS Hazard Statements

H315 (94.2%): Causes skin irritation [Warning Skin corrosion/irritation]

H317 (88.5%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H319 (94.2%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H334 (86.5%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

H335 (92.3%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P233, P260, P261, P264, P264+P265, P271, P272, P280, P284, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P403, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 52 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 2 of 52 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 9 notifications provided by 50 of 52 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

10.1.2 Hazard Classes and Categories

Skin Irrit. 2 (94.2%)

Skin Sens. 1 (88.5%)

Eye Irrit. 2 (94.2%)

Resp. Sens. 1 (86.5%)

STOT SE 3 (92.3%)

Skin Irrit. 2 (100%)

Skin Sens. 1 (100%)

Eye Irrit. 2 (97.5%)

Resp. Sens. 1 (97.5%)

STOT SE 3 (97.5%)

10.2 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt(1:1)
New Zealand EPA Inventory of Chemical Status
CF: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

11 Toxicity

11.1 Toxicological Information

11.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Leucovorin (folinic acid; 5-formyltetrahydrofolic acid) and its levo- isomer, levoleucovorin, are folic acid derivatives that are normal components of breastmilk. Because leucovorin and levoleucovorin are used as therapeutic agents with potentially toxic drugs such as fluorouracil or methotrexate, the LactMed record of the drug it is used with should be consulted.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

11.1.2 Acute Effects

11.1.3 Toxicity Data

ToxicityData
Mouse(iv): LD50 732 mg/kg
Drugs in Japan. Ethical Drugs. 6,910,(1982)

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Chemical Co-Occurrences in Literature

13.4 Chemical-Gene Co-Occurrences in Literature

13.5 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 Chemical Co-Occurrences in Patents

14.3 Chemical-Disease Co-Occurrences in Patents

14.4 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 WHO ATC Classification System

17.5 ChemIDplus

17.6 ChEMBL Target Tree

17.7 UN GHS Classification

17.8 NORMAN Suspect List Exchange Classification

17.9 CCSBase Classification

17.10 EPA DSSTox Classification

17.11 FDA Drug Type and Pharmacologic Classification

18 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt(1:1)
    https://services.industrialchemicals.gov.au/search-inventory/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  4. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    N-[4-[[(2-Amino-5-formyl-1,4,5,6,7,8- hexahydro-4-oxo-6-pteridinyl)-methyl]amino]benzoyl], L-glutamic Acid Calcium Salt pentahydrate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.228.231
    N-[4-[[(2-Amino-5-formyl-1,4,5,6,7,8- hexahydro-4-oxo-6-pteridinyl)-methyl]amino]benzoyl], L-glutamic Acid Calcium Salt pentahydrate (EC: 801-530-2)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/234758
  5. FDA Global Substance Registration System (GSRS)
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  6. New Zealand Environmental Protection Authority (EPA)
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    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  7. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  8. ChEBI
  9. NCI Thesaurus (NCIt)
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    https://platform-docs.opentargets.org/licence
  11. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  12. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  13. DailyMed
  14. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  15. Therapeutic Target Database (TTD)
  16. Drugs and Lactation Database (LactMed)
  17. Drugs@FDA
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    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  18. EU Clinical Trials Register
  19. FDA Orange Book
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  20. KEGG
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    https://www.kegg.jp/kegg/legal.html
  21. National Drug Code (NDC) Directory
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. NCI Cancer Drugs
  23. NCI Investigational Drugs
  24. NIPH Clinical Trials Search of Japan
  25. NLM RxNorm Terminology
    LICENSE
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  26. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  27. WHO Anatomical Therapeutic Chemical (ATC) Classification
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    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
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  29. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  30. PubChem
  31. GHS Classification (UNECE)
CONTENTS