Levoleucovorin

Identification

Name
Levoleucovorin
Accession Number
DB11596
Type
Small Molecule
Groups
Approved, Investigational
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.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Levoleucovorin calcium778XL6VBS880433-71-2KVUAALJSMIVURS-QNTKWALQSA-L
Levoleucovorin calcium pentahydrateWA16A5Y52X419573-16-3NPPBLUASYYNAIG-BWDMFOMUSA-L
Levoleucovorin disodium5TXQ76K65T1141892-29-6FSDMNNPYPVJNAT-NJHZPMQHSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FusilevInjection, solution10 mg/1mLIntravenousSpectrum Pharmaceuticals, Inc.2011-09-15Not applicableUs
FusilevInjection, powder, lyophilized, for solution50 mg/5mLIntravenousCangene Bio Pharma2008-08-152010-02-24Us
FusilevInjection, powder, lyophilized, for solution50 mg/5mLIntravenousSpectrum Pharmaceuticals, Inc.2008-08-15Not applicableUs
KhapzoryInjection, powder, lyophilized, for solution300 mg/6mLIntravenousSpectrum Pharmaceuticals, Inc.2019-01-02Not applicableUs
KhapzoryInjection, powder, lyophilized, for solution175 mg/3.5mLIntravenousSpectrum Pharmaceuticals, Inc.2019-01-02Not applicableUs
LevoleucovorinInjection, powder, lyophilized, for solution10 mg/1mLIntravenousActavis Pharma, Inc.2017-02-06Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LevoleucovorinInjection10 mg/1mLIntravenousGland Pharma Limited2018-09-20Not applicableUs
LevoleucovorinInjection, solution175 mg/17.5mLIntravenousDr.Reddy's Laboratories Inc2018-09-26Not applicableUs
LevoleucovorinInjection, solution10 mg/1mLIntravenousIngenus Pharmaceuticals, LLC2018-05-08Not applicableUs
LevoleucovorinInjection, solution250 mg/25mLIntravenousNorthstar RxLLC2018-09-26Not applicableUs
LevoleucovorinInjection, solution175 mg/17.5mLIntravenousSandoz2015-04-23Not applicableUs
LevoleucovorinInjection, powder, lyophilized, for solution50 mg/5mLIntravenousWest-Ward Pharmaceuticals Corp2016-07-07Not applicableUs
LevoleucovorinInjection, powder, lyophilized, for solution50 mg/1IntravenousAmneal Biosciences Llc2017-02-13Not applicableUs
LevoleucovorinInjection, solution10 mg/1mLIntravenousIngenus Pharmaceuticals, LLC2018-05-08Not applicableUs
LevoleucovorinInjection, solution175 mg/17.5mLIntravenousNorthstar RxLLC2018-09-26Not applicableUs
LevoleucovorinInjection, solution250 mg/25mLIntravenousDr.Reddy's Laboratories Inc2018-09-26Not applicableUs
Categories
UNII
990S25980Y
CAS number
68538-85-2
Weight
Average: 473.4393
Monoisotopic: 473.165896125
Chemical Formula
C20H23N7O7
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[C@H](CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2C=O)N1

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
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
UDihydrofolate reductaseNot AvailableEscherichia coli (strain K12)
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.

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.

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
DrugInteraction
5-FluorouridineThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with 5-Fluorouridine.
CapecitabineThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Capecitabine.
DoxifluridineThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Doxifluridine.
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.
TegafurThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Tegafur.
UracilThe risk or severity of adverse effects can be increased when Levoleucovorin is combined with Uracil.
Food Interactions
Not Available

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]
External Links
KEGG Drug
D04715
PubChem Compound
149436
PubChem Substance
347828002
ChemSpider
131714
BindingDB
286
ChEBI
63606
ChEMBL
CHEMBL1908841
PharmGKB
PA450198
HET
FFO
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Levoleucovorin
ATC Codes
V03AF10 — Sodium levofolinateV03AF04 — Calcium levofolinate
PDB Entries
1dfo / 1eqb / 1jol / 1jom / 1pj7 / 1wop / 2vmy / 3sd3 / 3suh / 3uwl
show 2 more
FDA label
Download (5.52 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentAdenocarcinoma of the Pancreas / Recurrent Pancreatic Carcinoma / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer / Unresectable Pancreatic Carcinoma1
1Active Not RecruitingTreatmentMucinous Adenocarcinoma of the Rectum / Rectal Adenocarcinoma / Recurrent Rectal Cancer / Signet Ring Adenocarcinoma of the Rectum / Stage IIA Rectal Cancer / Stage IIA to IIIC Rectal Cancer / Stage IIB Rectal Cancer / Stage IIC Rectal Cancer / Stage IIIA Rectal Cancer / Stage IIIB Rectal Cancer / Stage IIIC Rectal Cancer1
1CompletedTreatmentMalignant Digestive System Neoplasm1
1CompletedTreatmentMetastatic Colon Cancer / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage IV Rectal Cancer1
1CompletedTreatmentRecurrent Colon Carcinoma / Recurrent Rectal Carcinoma / Stage IVA Colon Cancer / Stage IVA Rectal Cancer / Stage IVB Colon Cancer / Stage IVB Rectal Cancer1
1CompletedTreatmentSarcomas1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
1RecruitingTreatmentAdenocarcinoma of the Rectum / Cancer of Rectum / Cancer of the Rectum / Rectal Carcinoma / Rectum Cancer / Rectum Neoplasms1
1RecruitingTreatmentAdvanced Cancers / Advanced Malignant Neoplasm / Recurrent Malignant Neoplasm / Refractory Malignant Neoplasm1
1RecruitingTreatmentCarcinoma, Colorectal / Colorectal Cancers / Colorectal Tumors / Neoplasms, Colorectal1
1TerminatedTreatmentMetastatic Colon Cancer / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage IV Rectal Cancer1
1WithdrawnPreventionLung Cancer Non-Small Cell Cancer (NSCLC)1
1WithdrawnPreventionNon Hodgkin Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic / Recurrent Pancreatic Carcinoma / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer1
1, 2CompletedTreatmentAdenocarcinoma of the Esophagus / Adenocarcinomas of the Gastroesophageal Junction / Advanced Gastric Cancer / Diffuse Adenocarcinoma of the Stomach / Intestinal Adenocarcinoma of the Stomach / Mixed Adenocarcinoma of the Stomach / Recurrent Esophageal Cancer / Recurrent Gastric Cancer / Stage IV Esophageal Cancer1
1, 2CompletedTreatmentColonic Neoplasms1
1, 2CompletedTreatmentGastrooesophageal Cancer / Malignant Solid Tumours1
1, 2CompletedTreatmentMetastatic Pancreas Adenocarcinoma1
1, 2Not Yet RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Biliary System Disorder / BRCA1 Gene Mutation / Brca2 Gene Mutation / Homologous Recombination Deficiency / PALB2 Gene Mutation / Pancreatic Adenocarcinoma Metastatic / Stage IV Colorectal Cancer AJCC v7 / Stage IV Pancreatic Cancer AJCC v6 and v7 / Stage IVA Colorectal Cancer AJCC v7 / Stage IVB Colorectal Cancer AJCC v71
1, 2RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Gastric Cardia Adenocarcinoma / Malignant Neoplasm of Stomach Stage II / Stage IB Gastric Cancer / Stage IB Gastric Cancer AJCC v7 / Stage II Gastric Cancer AJCC v7 / Stage IIA Gastric Cancer / Stage IIA Gastric Cancer AJCC v7 / Stage IIB Gastric Cancer / Stage IIB Gastric Cancer AJCC v7 / Stage IIIA Gastric Cancer / Stage IIIA Gastric Cancer AJCC v7 / Stage IIIB Gastric Cancer / Stage IIIB Gastric Cancer AJCC v71
1, 2RecruitingTreatmentDigestive Cancers1
2Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult Acute Lymphoblastic Leukemia in Remission / Adult B Acute Lymphoblastic Leukemia / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Adult L1 Acute Lymphoblastic Leukemia / Adult L2 Acute Lymphoblastic Leukemia / Adult T Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia1
2Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Untreated Adult Acute Lymphoblastic Leukemia1
2Active Not RecruitingTreatmentAdenocarcinoma of the Pancreas / Resectable Pancreatic Cancers / Resectable Pancreatic Carcinoma / Stage I Pancreatic Cancer / Stage IA Pancreatic Cancer / Stage IB Pancreatic Cancer / Stage II Pancreatic Cancer / Stage IIA Pancreatic Cancer / Stage IIB Pancreatic Cancer / Stage III Pancreatic Cancer1
2Active Not RecruitingTreatmentAdult Cholangiocarcinoma / Advanced Adult Hepatocellular Carcinoma / BCLC Stage C Adult Hepatocellular Carcinoma / BCLC Stage D Adult Hepatocellular Carcinoma / Hilar Cholangiocarcinoma / Localized Non-Resectable Adult Liver Carcinoma / Recurrent Adult Liver Carcinoma / Recurrent Childhood Liver Cancer / Recurrent Extrahepatic Bile Duct Carcinoma / Recurrent Gallbladder Carcinoma / Stage II Gallbladder Cancer / Stage III Childhood Hepatocellular Carcinoma / Stage IIIA Gallbladder Cancer / Stage IIIB Gallbladder Cancer / Stage IV Childhood Hepatocellular Carcinoma / Stage IV Distal Bile Duct Cancer / Stage IVA Gallbladder Cancer / Stage IVB Gallbladder Cancer / Unresectable Extrahepatic Bile Duct Carcinoma1
2Active Not RecruitingTreatmentNeoplasms, Esophageal / Stomach Neoplasms1
2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic / Recurrent Pancreatic Carcinoma / Stage IV Pancreatic Cancer / Stage IV Pancreatic Cancer AJCC v6 and v71
2Active Not RecruitingTreatmentRectal Adenocarcinoma / Stage II Rectal Cancer / Stage II Rectal Cancer AJCC v7 / Stage III Rectal Cancer / Stage III Rectal Cancer AJCC v71
2Active Not RecruitingTreatmentRectal Carcinoma1
2CompletedTreatmentAdenocarcinoma of the Colon / Adenocarcinoma of the Rectum / Metastatic Colon Cancer / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage IV Rectal Cancer1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentEpstein Barr Virus Associated Hodgkin's Lymphoma / Epstein Barr Virus Associated Non Hodgkin's Lymphoma / Post-transplant Lymphoproliferative Disease (PTLD)1
2CompletedTreatmentLeukemias2
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMalignant Neoplasm of Stomach2
2CompletedTreatmentNeoplasms, Esophageal / Stomach Neoplasms1
2CompletedTreatmentRecurrent Extragonadal Seminoma / Recurrent Malignant Extragonadal Germ Cell Tumor / Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor / Recurrent Malignant Testicular Germ Cell Tumor / Recurrent Ovarian Germ Cell Tumor / Stage III Testicular Cancer / Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor / Stage IV Extragonadal Seminoma / Stage IV Ovarian Germ Cell Tumor1
2Not Yet RecruitingTreatmentColonic Neoplasms / Neoplasms Metastasis / Neoplasms, Colorectal / Rectal Neoplasms1
2Not Yet RecruitingTreatmentMetastatic Colorectal Cancers1
2RecruitingTreatmentAdenocarcinoma of the Pancreas / Stage IIA Pancreatic Cancer / Stage IIB Pancreatic Cancer / Stage III Pancreatic Cancer1
2RecruitingTreatmentMalignant Neoplasm of Colon1
2RecruitingTreatmentRectal Adenocarcinoma / Stage II Rectal Cancer / Stage II Rectal Cancer AJCC v7 / Stage III Rectal Cancer / Stage III Rectal Cancer AJCC v71
2SuspendedTreatmentAcute Leukemias of Ambiguous Lineage / Childhood B Acute Lymphoblastic Leukemia / KMT2A Gene Rearrangement / Mixed Phenotype Acute Leukemia (MPAL)1
2TerminatedTreatmentAdenocarcinoma Of Esophagus / Adenocarcinoma of the Esophagus / Adenocarcinomas of the Gastroesophageal Junction / Stage II Esophageal Cancer / Stage IIA Esophageal Cancer / Stage IIB Esophageal Cancer1
2TerminatedTreatmentMalignant Neoplasm of Pancreas / Pancreatic Carcinoma Non-resectable1
2TerminatedTreatmentRecurrent Colorectal Carcinoma / Stage IVA Colorectal Cancer / Stage IVB Colorectal Cancer1
2, 3CompletedTreatmentAdult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Untreated Adult 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 Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Childhood B Lymphoblastic Lymphoma / Down Syndrome (DS) / Hypodiploid B Acute Lymphoblastic Leukemia / Intrachromosomal Amplification of Chromosome 21 / Philadelphia Chromosome Positive / Stage I B Lymphoblastic Lymphoma / Stage II B Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentAmpullary Cancer / Biliary Tract Cancer / Cholangiocarcinomas / Gallbladder Cancer1
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 / Stage IIA Colon Cancer AJCC v7 / Stage IIB Colon Cancer / Stage IIB Colon Cancer AJCC v7 / Stage IIC Colon Cancer / Stage IIC Colon Cancer AJCC v71
3Active Not RecruitingTreatmentLocally Advanced Malignant Neoplasm / Malignant Neoplasm of Pancreas / Pancreatic Carcinoma Non-resectable1
3Active Not RecruitingTreatmentMalignant Lymphomas1
3CompletedSupportive CareCardiac Toxicity / Leukemias / Malignant Lymphomas1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Undifferentiated Leukemia (AUL) / Childhood T Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult T Acute Lymphoblastic Leukemia / Ann Arbor Stage II Adult T-Cell Leukemia/Lymphoma / Ann Arbor Stage II Childhood Lymphoblastic Lymphoma / Ann Arbor Stage II Contiguous Adult Lymphoblastic Lymphoma / Ann Arbor Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Adult T-Cell Leukemia/Lymphoma / Ann Arbor Stage III Childhood Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult T-Cell Leukemia/Lymphoma / Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma / Childhood T Acute Lymphoblastic Leukemia / Stage II Adult T-Cell Leukemia/Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / T Acute Lymphoblastic Leukemia / T Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3CompletedTreatmentLeukemias2
3CompletedTreatmentLeukemias / Malignant Lymphomas1
3CompletedTreatmentMalignant Lymphomas1
3Not Yet RecruitingTreatmentColorectal Adenocarcinoma / RAS Wild Type / Stage III Colorectal Cancer AJCC v7 / Stage IIIA Colorectal Cancer AJCC v7 / Stage IIIB Colorectal Cancer AJCC v7 / Stage IIIC Colorectal Cancer AJCC v7 / Stage IV Colorectal Cancer AJCC v7 / Stage IVA Colorectal Cancer AJCC v7 / Stage IVB Colorectal Cancer AJCC v71
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / BCR-ABL1 Fusion Protein Expression / Minimal Residual Disease / Philadelphia Chromosome Positive / T Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Cognitive Side Effects of Cancer Therapy / Neurotoxicity Syndrome / Osteonecrosis / Pain NOS / Ph-Like Acute Lymphoblastic Leukemia / Testicular Leukemia / Therapy-Related Toxicity / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Cognitive Side Effects of Cancer Therapy / Neurotoxicity Syndrome / Osteonecrosis / Pain NOS / Testicular Leukemia / Therapy-Related Toxicity / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentColon Adenocarcinoma / DNA Repair Disorder / Lynch Syndrome / Microsatellite Instability / Stage III Colon Cancer AJCC v7 / Stage IIIA Colon Cancer / Stage IIIA Colon Cancer AJCC v7 / Stage IIIB Colon Cancer / Stage IIIB Colon Cancer AJCC v7 / Stage IIIC Colon Cancer / Stage IIIC Colon Cancer AJCC v71
3RecruitingTreatmentColorectal Adenocarcinoma / High-Frequency Microsatellite Instability / Mismatch Repair Deficiency / Stage IV Colorectal Cancer / Stage IV Colorectal Cancer AJCC v7 / Stage IVA Colorectal Cancer / Stage IVA Colorectal Cancer AJCC v7 / Stage IVB Colorectal Cancer / Stage IVB Colorectal Cancer AJCC v71
3RecruitingTreatmentColorectal Cancers2
3SuspendedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult 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 Leukemia / Stage II Adult Lymphoblastic Lymphoma / Stage II Childhood Lymphoblastic Lymphoma / Stage II Contiguous Adult Lymphoblastic Lymphoma / Stage II Non-Contiguous Adult Lymphoblastic Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Childhood Lymphoblastic Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Childhood Lymphoblastic Lymphoma / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3TerminatedTreatmentColorectal Cancers1
Not AvailableCompletedTreatmentLeukemias1
Not AvailableNot Yet RecruitingTreatmentAdvanced Gastric Cancer Adenocarcinoma of Esophagogastric Junction1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous50 mg/5mL
Injection, solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous175 mg/3.5mL
Injection, powder, lyophilized, for solutionIntravenous300 mg/6mL
InjectionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/1
Injection, solutionIntravenous175 mg/17.5mL
Injection, solutionIntravenous250 mg/25mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6500829No2002-12-312022-03-07Us

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

Taxonomy

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
Tetrahydrofolic acid / Glutamic acid or derivatives / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid / Hippuric acid / Hippuric acid or derivatives / Alpha-amino acid or derivatives / Aminobenzamide / Aminobenzoic acid or derivatives / Benzamide
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
5-formyltetrahydrofolic acid (CHEBI:63606)

Targets

Kind
Protein
Organism
Shigella flexneri
Pharmacological action
Unknown
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
General Function
Nadp binding
Specific Function
Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
Gene Name
folA
Uniprot ID
P0ABQ4
Uniprot Name
Dihydrofolate reductase
Molecular Weight
17999.21 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on May 19, 2016 13:51 / Updated on January 20, 2019 02:21