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

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 32 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 8297
Dihydrofolate reductase 57 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 1430

Conditions

Condition	Modality	Highest Phase	Product
Osteosarcoma 22 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040347s010lbl.pdf	Secondary	Approved 8429	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 8429	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 8429	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
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
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
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:		LEUCOVORIN CALCIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
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
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
1810 mg × 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 CALCIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
100 mg 1 times / day single, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: single Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10932085/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf	healthy, 32 years n = 1 Health Status: healthy Age Group: 32 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/10932085/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf	Other AEs: Urticaria... Other AEs: Urticaria Sources: https://pubmed.ncbi.nlm.nih.gov/10932085/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf
1000 mg/m2 8 times / day multiple, intravenous Highest studied dose Dose: 1000 mg/m2, 8 times / day Route: intravenous Route: multiple Dose: 1000 mg/m2, 8 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21509165/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf	unhealthy, 7 years old n = 1 Health Status: unhealthy Condition: osteosarcoma Age Group: 7 years old Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21509165/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf	Sources: https://pubmed.ncbi.nlm.nih.gov/21509165/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf
200 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11996482/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf	unhealthy, 80 years n = 1 Health Status: unhealthy Condition: colon cancer Age Group: 80 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11996482/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf	Disc. AE: Anaphylactic shock... AEs leading to discontinuation/dose reduction: Anaphylactic shock Sources: https://pubmed.ncbi.nlm.nih.gov/11996482/ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/020140s000medR.pdf
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 Co-administed with:: fluorouracil(320 mg/m2 IV; 1 per week) oxaliplatin(50 mg/m2 IV; on days 1 and 15 every 6 weeks) CPT-11(75 mg/m2 IV: 1 per week) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years n = 6 Health Status: unhealthy Condition: advanced solid tumors Age Group: Median age 52 years Sex: M+F Population Size: 6 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 Co-administed with:: fluorouracil(425 mg/m2 IV; 1 per week) oxaliplatin(70 mg/m2 IV; on days 1 and 15 every 6 weeks) CPT-11(100 mg/m2 IV: 1 per week) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years n = 4 Health Status: unhealthy Condition: advanced solid tumors Age Group: Median age 52 years Sex: M+F Population Size: 4 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 Co-administed with:: fluorouracil(425 mg/m2 IV; 1 week) oxaliplatin(70 mg/m2 IV; on days 1 and 15 every 6 weeks) CPT-11(100 mg/m2 IV: 1 per week) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years n = 4 Health Status: unhealthy Condition: advanced solid tumors Age Group: Median age 52 years Sex: M+F Population Size: 4 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 Co-administed with:: fluorouracil(320 mg/m2 IV; 1 per week) oxaliplatin(70 mg/m2 IV; on days 1 and 15 every 6 weeks) CPT-11(70 mg/m2 IV: 1 per week) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 52 years n = 3 Health Status: unhealthy Condition: advanced solid tumors Age Group: Median age 52 years Sex: M+F Population Size: 3 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 Co-administed with:: fluorouracil(240 mg/m2 IV; days 2 to 5 every 3 weeks) oxaliplatin(110 mg/m2 IV; 1st day every 3 weeks) CPT-11(250 mg/m2 IV: 1st day every 3 weeks) Sources: https://ascopubs.org/doi/abs/10.1200/jco.2003.01.238	unhealthy, Median age 60.5 years n = 3 Health Status: unhealthy Condition: advanced solid tumors Age Group: Median age 60.5 years Sex: M+F Population Size: 3 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
BSEP 402 MRP2 383 MRP3 157 MRP4 204 OATP1B1 788 OATP1B3 706	MRP3 50 MRP4 77	MRP2 111

Drug as perpetrator

Target	Modality	Activity
BSEP 403	inhibitor 3277 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 475	inhibitor 3277 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 207	inhibitor 3277 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 238	inhibitor 3277 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 475	inducer 1573 Sources: https://pubs.acs.org/doi/pdf/10.1021/jm7015683#page=3 Page: -	no
OATP1B1 803	inhibitor 3277 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP3 50	substrate 3367 Sources: https://cancerres.aacrjournals.org/content/61/19/7225.full-text.pdf Page: -	no [Km 1740 uM]
MRP4 77	substrate 3367 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
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
Achemtek	0102-026003	http://www.achemtek.com/58-05-9
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
CSNpharm	CSN10090	https://www.csnpharm.com/products/folinic-acid.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
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
abcr GmbH	AB524413	http://www.abcr.com/shop/en/AB524413
eNovation Chemicals	D671707	https://www.enovationchem.com/ProductDetails.asp?ProductID=D671707
eNovation Chemicals	D783523	https://www.enovationchem.com/ProductDetails.asp?ProductID=D783523

PubMed

Title	Date	PubMed
Transient cerebral dysfunction following chemotherapy for osteogenic sarcoma.	1978 May	310278
Effects of intraventricular methotrexate on cerebrospinal fluid monoamine metabolites in rhesus monkeys.	1986 Oct	2428491
Leukocytoclastic vasculitis after high-dose methotrexate.	1986 Sep	3461742
Valproic acid-induced neural tube defects: reduction by folinic acid in the mouse.	1987 Jul 6	3110521
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
High dose intravenous methotrexate and reversible focal neurological deficit.	1990 Dec	2265121
Dose response relationship of methotrexate in combination with cisplatin in murine bladder cancer.	1990 Mar	2316090
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
Clinical use of thymidine as a rescue agent from methotrexate toxicity.	1991 Aug	1838364
Carboxypeptidase-G2 rescue in a patient with high dose methotrexate-induced nephrotoxicity.	2005 Apr	19956493
Mitochondrial complex I encephalomyopathy and cerebral 5-methyltetrahydrofolate deficiency.	2007 Aug	18058625
Successful carboxypeptidase G2 rescue of a high-risk elderly Hodgkin lymphoma patient with methotrexate intoxication and renal failure.	2007 Aug	17701600
First clinical experience of orally active epidermal growth factor receptor inhibitor combined with simplified FOLFOX6 as first-line treatment for metastatic colorectal cancer.	2007 Aug 15	17594712
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 Dec	18211984
Severe methotrexate toxicity precipitated by intravenous radiographic contrast.	2007 Jul	17609630
Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use.	2007 Jun 1	17519458
A pilot phase II study of chemotherapy with oxaliplatin, folinic acid, 5-fluorouracil and irinotecan in metastatic gastric cancer.	2007 May-Jun	17679458
Methotrexate/naproxen-associated severe hepatitis in a child with juvenile idiopathic arthritis.	2007 Nov-Dec	18173932
K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy.	2008 Aug 1	18676755
Early recognition of renal toxicity of high-dose methotrexate therapy: a case report.	2008 Dec	19131789
Protein expression profiling in esophageal adenocarcinoma patients indicates association of heat-shock protein 27 expression and chemotherapy response.	2008 Dec 15	19088045
[Genetic polymorphisms related to fluoropyrimidine sensitivity and toxicity].	2008 Jul	18633250
Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis.	2008 Nov 15	18997139
A 50-year-old man with burkitt lymphoma.	2008 Oct	18782177
Fatal thrombocytopenia after oxaliplatin-based chemotherapy.	2008 Sep-Oct	19031966
An unusual presentation of hand-foot syndrome at the hidden area: the scrotum and penis.	2009	19330576
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 Aug	19736586
Phase I study of flavopiridol with oxaliplatin and fluorouracil/leucovorin in advanced solid tumors.	2009 Dec 1	19934304
[A case of therapy for bevacizumab-induced hypertension].	2009 Jan	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 Jan	18976724
Second-line therapy in refractory pancreatic cancer. results of a phase II study.	2009 Mar	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 Mar	19074750
Acute methotrexate neurotoxicity with choreiform movements and focal neurological deficits: a case report.	2009 Oct	19738521
Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient with acute renal failure.	2009 Oct-Nov	19863208
Exploratory study of hepatic arterial infusion oxaliplatin with systemic 5-fluorouracil/bevacizumab in patients with refractory solid tumor and extensive liver metastases.	2010 Dec	21208846
A phase I study of 5-fluorouracil/leucovorin and arsenic trioxide for patients with refractory/relapsed colorectal carcinoma.	2010 Jun 1	20501625
Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites.	2010 May	19821069
Interleukin-10 and -12 predict chemotherapy-associated toxicity in esophageal adenocarcinoma.	2010 Nov	20881642
Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma.	2010 Nov	20180123
Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome.	2010 Sep 1	20679598
Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.	2011 Feb 11	21310277
Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.	2011 Feb 11	21310276
Effect of methotrexate and leucovorin on female reproductive tract of albino rats.	2011 Jan-Feb	21213337
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 Oct 27	21879757
Prognostic and predictive role of JWA and XRCC1 expressions in gastric cancer.	2012 May 15	22452940
Low-dose methotrexate inhibits methionine S-adenosyltransferase in vitro and in vivo.	2012 May 9	22193356
Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937.	2014 Jan 20	24444433
Methotrexate-induced bone marrow adiposity is mitigated by folinic acid supplementation through the regulation of Wnt/β-catenin signalling.	2015 Mar	25187349

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.

Name

Type

Language

LEUCOVORIN

Common 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

FOLINIC 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