LEUCOVORIN

First approved in 1952

Details

Stereochemistry	EPIMERIC
Molecular Formula	C20H23N7O7
Molecular Weight	473.4393
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)C2=C(NCC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2C=O)N1

InChI

InChIKey=VVIAGPKUTFNRDU-ABLWVSNPSA-N

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

HIDE SMILES / InChI

Molecular Formula	C20H23N7O7
Molecular Weight	473.4393
Charge	0
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry	No
Defined Stereocenters	1 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://chemocare.com/chemotherapy/drug-info/Leucovorin.aspx

Leucovorin is a compound similar to folic acid, which is a necessary vitamin. It has been around and in use for many decades. Leucovorin is a medication frequently used in combination with the chemotherapy drugs fluoruracil and methotrexate. Leucovorin is not a chemotherapy drug itself, however it is used in addition to these chemotherapy drugs to enhance anticancer effects (with fluorouracil) or to help prevent or lessen side effects (with methotrexate). Leucovorin is also used by itself to treat certain anemia problems when folic acid deficiency is present.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidylate synthase 33 Target ID: P04818 Gene ID: 7298.0 Gene Symbol: TYMS Target Organism: Homo sapiens (Human) Sources: https://www.cancercare.on.ca/CCO_DrugFormulary/Pages/DfPdfContent.aspx?itemId=93949.	Inhibitor 8504
Dihydrofolate reductase 61 Target ID: P00374 Gene ID: 1719.0 Gene Symbol: DHFR Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/2260989	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Osteosarcoma 22 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	Secondary	Approved 8583	LEUCOVORIN CALCIUM Approved Use Leucovorin rescue is indicated after high dose methotrexate therapy in osteosarcoma. Leucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Leucovorin is indicated in the treatment of megaloblastic anemias due to folic acid deﬁciency when oral therapy is not feasible. Leucovorin is also indicated for use in combination with 5-ﬂuorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Launch Date 1953
Megaloblastic anemia 9 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	Palliative	Approved 8583	LEUCOVORIN CALCIUM Approved Use Leucovorin rescue is indicated after high dose methotrexate therapy in osteosarcoma. Leucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Leucovorin is indicated in the treatment of megaloblastic anemias due to folic acid deﬁciency when oral therapy is not feasible. Leucovorin is also indicated for use in combination with 5-ﬂuorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Launch Date 1953
Advanced colorectal cancer 8 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	Palliative	Approved 8583	LEUCOVORIN CALCIUM Approved Use Leucovorin rescue is indicated after high dose methotrexate therapy in osteosarcoma. Leucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. Leucovorin is indicated in the treatment of megaloblastic anemias due to folic acid deﬁciency when oral therapy is not feasible. Leucovorin is also indicated for use in combination with 5-ﬂuorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. Launch Date 1953

C_max

Value	Dose	Co-administered	Analyte	Population
391 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LEUCOVORIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
258 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
226 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
360 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		LEUCOVORIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
96 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / week other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
51 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / 5 weeks other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1810 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
65.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8405015/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LEUCOVORIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.4 mg × min/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
71 mM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / week other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
364 mM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / 5 weeks other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
6.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		5-METHYLTETRAHYDROFOLIC ACID serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
6.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		LEUCOVORIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3260621	500 mg/m² 1 times / week other, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: OTHER co-administered: FLUOROURACIL	FLUOROURACIL	LEUCOVORIN CALCIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg/m2 1 times / week multiple, intravenous MTD Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	Other AEs: Neurotoxicity, Diarrhea... Other AEs: Neurotoxicity (grade 1, 83.3%) Diarrhea (grade 1, 66.7%) Diarrhea (grade 3, 16.7%) Nausea (grade 1, 16.7%) Nausea (grade 2, 33.3%) Vomiting (grade 1, 33.3%) Vomiting (grade 2, 16.7%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (20%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 3, 40%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / week Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years Health Status: unhealthy Age Group: Median age 52 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 3, 33.3%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238
20 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 60.5 years Health Status: unhealthy Age Group: Median age 60.5 years Sex: M+F Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 33.3%) Vomiting (grade 3, 33.3%) Diarrhea (grade 3, 33.3%) Paresthesia (grade 3, 33.3%) Febrile neutropenia (grade 4, 33.3%) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 499 MRP3 246 MRP4 290 OATP1B1 1079 OATP1B3 961 BSEP 550	MRP3 58 MRP4 91	MRP2 146

Drug as perpetrator

Target	Modality	Activity
BSEP 554	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP2 625	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP3 326	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP4 345	inhibitor 4027 Sources: https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/toxsci/136/1/10.1093_toxsci_kft176/4/kft176_Supplementary_Data.zip?Expires=1609319785&Signature=x1NTqcf30eQNwNXLbTJYuSlrhXJOTPCD4E1rpNdByUGpvcca3Q0cLAIYJf2Be1CQmt7HigeN8KogwXsVK~U6sgAQ4gEq1Ut74WiOVlyE6PhlJ6Sw5W6kcg9CJamWWk6RdaPPXpIYdojE~QwMcVfDRelILEK9fP3U~ZisWoRgrhkRavh9q3uTAyRUaGxj5JRVRLAQvIy4yJ3IRESloet-SccuaSjLTfRoiP8tFIME2qmmyyM3~ofqhr~deMat0UJkPGuPcE26zkr-7y8CsBuqALhHY-spzvYpwhQQJMNuwctqd1w-3gifDVc99IG7p5HB9q559ZOS42yQEr7i-oXJ4w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA Page: -	no [IC50 133 uM]
MRP2 625	inducer 1966 Sources: https://pubs.acs.org/doi/pdf/10.1021/jm7015683#page=3 Page: -	no
OATP1B1 1095	inhibitor 4027 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP3 58	substrate 4014 Sources: https://cancerres.aacrjournals.org/content/61/19/7225.full-text.pdf Page: -	no [Km 1740 uM]
MRP4 91	substrate 4014 Sources: https://cancerres.aacrjournals.org/content/62/11/3144.full-text.pdf#page=4 Page: -	no [Km 640 uM]

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1408	http://www.3bsc.com/index/pro_info.php?id=55124
abcr GmbH	AB524413	http://www.abcr.com/shop/en/AB524413
Achemtek	0102-026003	http://www.achemtek.com/58-05-9
AEchem Scientific Corp., USA	AE045500	http://www.aechemsc.com/info_products/AE045500.php
AHH Chemical co.,ltd	MT-53184	http://www.ahhchemical.com/product/MT-53184.html
Alsachim	4281	http://www.alsachim.com/product-C5599-glo.bal-view.html
Aurora Fine Chemicals LLC	A24.077.515	http://online.aurorafinechemicals.com/info?ID=A24.077.515
BLD Pharm	BD105751	http://www.bldpharm.com/products/58-05-9.html
Boerchem	BC206228	http://www.boerchem.com/?product_34779.html
Chem Scene	CS-2989	http://www.chemscene.com/58-05-9.html
ChemMol	30103057	http://www.chemmol.com/chemmol/30103057.html
ChemMol	44002424	http://www.chemmol.com/chemmol/44002424.html
Chemspace	CSSB00102462341	https://chem-space.com/CSSB00102462341
Combi-Blocks	QW-7315	http://www.combi-blocks.com/cgi-bin/find.cgi?QW-7315
CSNpharm	CSN10090	https://www.csnpharm.com/products/folinic-acid.html
eNovation Chemicals	D671707	https://www.enovationchem.com/ProductDetails.asp?ProductID=D671707
eNovation Chemicals	D783523	https://www.enovationchem.com/ProductDetails.asp?ProductID=D783523
Hairui	HR129597	http://www.hairuichem.com/en/product/58-05-9.html
Lab Network	LN01296494	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01296494
MedChem Express	HY-17556	https://www.medchemexpress.com/folinic-acid.html
MuseChem	I001836	https://www.musechem.com/product/I001836.html
Selleck Chemicals	S5790	http://www.selleckchem.com/products/folinic-acid.html
Yuhao Chemical	LL0016	http://www.chemyuhao.com/58-05-9.html

PubMed

Title	Date	PubMed
Methotrexate-induced bone marrow adiposity is mitigated by folinic acid supplementation through the regulation of Wnt/β-catenin signalling.	2015-03	25187349
Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937.	2014-01-20	24444433
Prognostic and predictive role of JWA and XRCC1 expressions in gastric cancer.	2012-05-15	22452940
Low-dose methotrexate inhibits methionine S-adenosyltransferase in vitro and in vivo.	2012-05-09	22193356
Synthesis, biological, and antitumor activity of a highly potent 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitor with proton-coupled folate transporter and folate receptor selectivity over the reduced folate carrier that inhibits β-glycinamide ribonucleotide formyltransferase.	2011-10-27	21879757
Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.	2011-02-11	21310277
Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.	2011-02-11	21310276
Effect of methotrexate and leucovorin on female reproductive tract of albino rats.	2011-01-08	21213337
Exploratory study of hepatic arterial infusion oxaliplatin with systemic 5-fluorouracil/bevacizumab in patients with refractory solid tumor and extensive liver metastases.	2010-12	21208846
Interleukin-10 and -12 predict chemotherapy-associated toxicity in esophageal adenocarcinoma.	2010-11	20881642
Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma.	2010-11	20180123
Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome.	2010-09-01	20679598
A phase I study of 5-fluorouracil/leucovorin and arsenic trioxide for patients with refractory/relapsed colorectal carcinoma.	2010-06-01	20501625
Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites.	2010-05	19821069
Phase I study of flavopiridol with oxaliplatin and fluorouracil/leucovorin in advanced solid tumors.	2009-12-01	19934304
Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient with acute renal failure.	2009-10-30	19863208
Acute methotrexate neurotoxicity with choreiform movements and focal neurological deficits: a case report.	2009-10	19738521
Prevention of neurotoxicity by high-dose folinic acid rescue after high-dose methotrexate and intrathecal methotrexate without compromising cure inspite of previous transient leukoencephalopathy after intrathecal methotrexate.	2009-08	19736586
Second-line therapy in refractory pancreatic cancer. results of a phase II study.	2009-03	19295247
Pharmacogenetic analyses of hematotoxicity in advanced gastric cancer patients receiving biweekly fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).	2009-03	19074750
[A case of therapy for bevacizumab-induced hypertension].	2009-01	19151582
Damaging effects of chronic low-dose methotrexate usage on primary bone formation in young rats and potential protective effects of folinic acid supplementary treatment.	2009-01	18976724
An unusual presentation of hand-foot syndrome at the hidden area: the scrotum and penis.	2009	19330576
Protein expression profiling in esophageal adenocarcinoma patients indicates association of heat-shock protein 27 expression and chemotherapy response.	2008-12-15	19088045
Early recognition of renal toxicity of high-dose methotrexate therapy: a case report.	2008-12	19131789
Fatal thrombocytopenia after oxaliplatin-based chemotherapy.	2008-11-27	19031966
Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis.	2008-11-15	18997139
A 50-year-old man with burkitt lymphoma.	2008-10	18782177
K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy.	2008-08-01	18676755
[Genetic polymorphisms related to fluoropyrimidine sensitivity and toxicity].	2008-07	18633250
Methotrexate/naproxen-associated severe hepatitis in a child with juvenile idiopathic arthritis.	2008-01-05	18173932
A Phase II study of oxaliplatin with low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) for gastric cancer patients with malignant ascites.	2007-12	18211984
First clinical experience of orally active epidermal growth factor receptor inhibitor combined with simplified FOLFOX6 as first-line treatment for metastatic colorectal cancer.	2007-08-15	17594712
A pilot phase II study of chemotherapy with oxaliplatin, folinic acid, 5-fluorouracil and irinotecan in metastatic gastric cancer.	2007-08-08	17679458
Mitochondrial complex I encephalomyopathy and cerebral 5-methyltetrahydrofolate deficiency.	2007-08	18058625
Successful carboxypeptidase G2 rescue of a high-risk elderly Hodgkin lymphoma patient with methotrexate intoxication and renal failure.	2007-08	17701600
Severe methotrexate toxicity precipitated by intravenous radiographic contrast.	2007-07	17609630
Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use.	2007-06-01	17519458
Carboxypeptidase-G2 rescue in a patient with high dose methotrexate-induced nephrotoxicity.	2005-04	19956493
Clinical use of thymidine as a rescue agent from methotrexate toxicity.	1991-08	1838364
Diurnal variation of folate concentrations in mouse embryo and plasma: the protective effect of folinic acid on valproic-acid-induced teratogenicity is time dependent.	1991	1810574
High dose intravenous methotrexate and reversible focal neurological deficit.	1990-12	2265121
Dose response relationship of methotrexate in combination with cisplatin in murine bladder cancer.	1990-03	2316090
Discoloration of the nails and early anemia after mitoxantrone, folinic acid and 5-fluorouracil.	1990	2283895
Folate nephropathy occurring during cytotoxic chemotherapy with high-dose folinic acid and 5-fluorouracil.	1990	2236732
Methotrexate-induced leukoencephalopathy is treatable with high-dose folinic acid: a case report and analysis of the literature.	1990	2204409
Valproic acid-induced neural tube defects: reduction by folinic acid in the mouse.	1987-07-06	3110521
Effects of intraventricular methotrexate on cerebrospinal fluid monoamine metabolites in rhesus monkeys.	1986-10	2428491
Leukocytoclastic vasculitis after high-dose methotrexate.	1986-09	3461742
Transient cerebral dysfunction following chemotherapy for osteogenic sarcoma.	1978-05	310278

Patents

Sample Use Guides

In Vivo Use Guide

200 mg/m2 or 20 mg/m2 in Advanced Colorectal Cancer, 10 mg/m2 in Leucovorin Rescue After High-Dose Methotrexate Therapy and up to 1 mg daily in Megaloblastic Anemia Due to Folic Acid Deﬁciency.

Route of Administration: Intravenous

In Vitro Use Guide

RPMI 1788 cells revealed a high intrinsic resistance to methotrexate (MTX). The cytotoxic effect of high concentrations of MTX (10 -5 M) was reversed by relatively low (10 -6 M) concentrations of simultaneously added leucovorin (LV). The enhancement of cell survival was less marked when LV application was delayed for 12 h.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:30:48 GMT 2025` Edited by `admin` on `Mon Mar 31 18:30:48 GMT 2025`
Record UNII	Q573I9DVLP
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEUCOVORIN

Common Name

English

FOLINIC ACID

Preferred Name

English

N-(P-((((6RS)-2-AMINO-5-FORMYL-5,6,7,8-TETRAHYDRO-4-HYDROXY-6-PTERIDINYL)METHYL)AMINO)BENZOYL)-L-GLUTAMATE

Common Name

English

FOLINIC ACID [MART.]

Common Name

English

Folinic acid [WHO-DD]

Common Name

English

5-FORMYLTETRAHYDROFOLIC ACID

Common Name

English

L-GLUTAMIC ACID, N-(4-(((2-AMINO-5-FORMYL-1,4,5,6,7,8-HEXAHYDRO-4-OXO-6-PTERIDINYL)METHYL)AMINO)BENZOYL)-

Common Name

English

LEUCOVORIN [HSDB]

Common Name

English

FOLINIC ACID [MI]

Common Name

English

5-FORMYLTETRAHYDROFOLATE

Common Name

English

LEUCOVORIN [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2078