Levoleucovorin calcium | CAS# 80433-71-2 (Ca) | antidote to folic acid

MedKoo Cat#: 413021 | Name: Levoleucovorin calcium

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

levoleucovorin is the levo isomeric form of racemic d,l-leucovorin,. Levoleucovorin is the pharmacologically active isomer of leucovorin [(6-S)-leucovorin]. levoleucovorin is the pharmacologically active isomer of 5-formyl tetrahydrofolic acid. levoleucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Administration of levoleucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase.levoleucovorin rescue is indicated after high-dose methotrexate therapy in osteosarcoma. levoleucovorin is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.

Chemical Structure

Levoleucovorin calcium

CAS# 80433-71-2 (calcium)

Theoretical Analysis

MedKoo Cat#: 413021

Name: Levoleucovorin calcium

CAS#: 80433-71-2 (calcium)

Chemical Formula: C20H22CaN7O7+

Exact Mass: 512.1201

Molecular Weight: 512.52

Elemental Analysis: C, 46.87; H, 4.33; Ca, 7.82; N, 19.13; O, 21.85

Price and Availability

Size	Price	Availability
250mg	USD 350.00	2 Weeks
500mg	USD 750.00	2 Weeks
1g	USD 1,250.00	2 Weeks

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Related CAS #

163254-40-8 (sodium) 80433-71-2 (calcium) 68538-85-2 (free acid)

Synonym

Levoleucovorin calcium; CL307,782; CL-307,782; CL 307,782

IUPAC/Chemical Name

Calcium N-(p-((((6S)-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-glutamate (1:1)

InChi Key

YPJRHVHBPOCWRL-MWQMLZFGSA-M

InChi Code

InChI=1S/C20H23N7O7.Ca/c21-20(8-23-16-15(27(20)10-28)18(32)25-9-24-16)7-22-12-3-1-11(2-4-12)17(31)26-13(19(33)34)5-6-14(29)30;/h1-4,9-10,13,22H,5-8,21H2,(H,26,31)(H,29,30)(H,33,34)(H2,23,24,25,32);/q;+2/p-1/t13-,20-;/m0./s1

SMILES Code

O=C(O)CC[C@@H](C([O-])=O)NC(C1=CC=C(NC[C@]2(N)N(C=O)C3=C(NC=NC3=O)NC2)C=C1)=O.[Ca+2]

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Levoleucovorin Calcium (Calcium levofolinate), a levo isoform of Leucovorin Calcium (HY-13664), possesses antineoplastic effects.

In vitro activity:

Folinic acid (Leucovorin) is generally administered along with MTX as a rescue agent to decrease MTX-induced toxicity. The addition of FA (folinic acid) at 50 micrograms ml-1 significantly reduced % MNBN (40-68%) and % Abs (36-77%). Inhibition was also seen at 5 micrograms FA (12 to 54% for MNBN and 20 to 61% for Abs). These results indicate that FA is capable of reducing the cytogenetic damage induced by MTX and appears to be an anticlastogenic agent. Reference: Mutat Res. 1998 Feb 2;397(2):221-8. https://pubmed.ncbi.nlm.nih.gov/9541646/

In vivo activity:

These data show that chronic administration of MTX induces suppression of skeletal growth in mice, possibly through the inhibition of the pathway of de novo DNA synthesis. Folinic acid treatment following MTX administration appears to reverse this growth inhibition. Reference: Acta Paediatr. 2003 Dec;92(12):1438-44. https://pubmed.ncbi.nlm.nih.gov/14971796/

	Solvent	mg/mL	mM	comments
Solubility
	Water	5.2	10.05

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 512.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Tedeschi PM, Kathari YK, Farooqi IN, Bertino JR. Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts. Cancer Chemother Pharmacol. 2014 Nov;74(5):1029-32. doi: 10.1007/s00280-014-2580-z. Epub 2014 Sep 9. PMID: 25205429; PMCID: PMC4209237. 2. Keshava C, Keshava N, Whong WZ, Nath J, Ong TM. Inhibition of methotrexate-induced chromosomal damage by folinic acid in V79 cells. Mutat Res. 1998 Feb 2;397(2):221-8. doi: 10.1016/s0027-5107(97)00216-9. PMID: 9541646. 3. Iqbal MP, Ahmed M, Umer M, Mehboobali N, Qureshi AA. Effect of methotrexate and folinic acid on skeletal growth in mice. Acta Paediatr. 2003 Dec;92(12):1438-44. PMID: 14971796. 4. Van der Wilt CL, Pinedo HM, Smid K, Peters GJ. Elevation of thymidylate synthase following 5-fluorouracil treatment is prevented by the addition of leucovorin in murine colon tumors. Cancer Res. 1992 Sep 15;52(18):4922-8. PMID: 1516048.

In vitro protocol:

In vivo protocol:

1. Iqbal MP, Ahmed M, Umer M, Mehboobali N, Qureshi AA. Effect of methotrexate and folinic acid on skeletal growth in mice. Acta Paediatr. 2003 Dec;92(12):1438-44. PMID: 14971796. 2. Van der Wilt CL, Pinedo HM, Smid K, Peters GJ. Elevation of thymidylate synthase following 5-fluorouracil treatment is prevented by the addition of leucovorin in murine colon tumors. Cancer Res. 1992 Sep 15;52(18):4922-8. PMID: 1516048.

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FOLFOX regimen after failure of fluorouracil and leucovorin plus nanoliposomal-irinotecan therapy for advanced pancreatic cancer: a retrospective observational study. BMC Cancer. 2023 Feb 21;23(1):177. doi: 10.1186/s12885-023-10654-3. PMID: 36809997; PMCID: PMC9945590. 5: Qiu B, Liu G, Wang C, Chen X, Liu R, Huang Y, Jia Y, Shen J. Three-Period Bioequivalence Study of Sodium Levofolinate Injection With Calcium Levofolinate for Injection and Sodium Folinate for Injection in Healthy Chinese Subjects. Clin Pharmacol Drug Dev. 2023 Apr;12(4):416-423. doi: 10.1002/cpdd.1223. Epub 2023 Feb 19. PMID: 36808267. 6: Su L, Zhao S, Yin Y, Huang F, Zhu J, Chen L; FNF Independent Investigations Group; Lin R. POF (paclitaxel/oxaliplatin/5-fluorouracil/leucovorin) vs. SOX/CAPOX/FOLFOX as a postoperative adjuvant chemotherapy for curatively resected stage III gastric cancer: Study protocol for a randomized controlled trial, FNF-014 trial. 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PMID: 34304979. 10: Cirronis M, Novara E, Persiano T, Perlini S, Locatelli CA. Bowel perforation due to methotrexate therapeutic error: an insidious adverse reaction. Eur Rev Med Pharmacol Sci. 2021 Mar;25(5):2344-2347. doi: 10.26355/eurrev_202103_25273. PMID: 33755972. 11: Satake H, Ando K, Oki E, Shimokawa M, Makiyama A, Saeki H, Tsuji A, Mori M. Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer. BMC Cancer. 2020 Nov 17;20(1):1116. doi: 10.1186/s12885-020-07576-9. PMID: 33203393; PMCID: PMC7672899. 12: Peters GJ, van Gemert FPA, Kathmann I, Reddy G, Cillessen SAGM, Jansen G. Schedule-Dependent Synergy Between the Histone Deacetylase Inhibitor Belinostat and the Dihydrofolate Reductase Inhibitor Pralatrexate in T-and B-cell Lymphoma Cells in vitro. Front Cell Dev Biol. 2020 Oct 9;8:577215. doi: 10.3389/fcell.2020.577215. PMID: 33163492; PMCID: PMC7581941. 13: Sanogo S, Silimbani P, Gaggeri R, Masini C. Stability of calcium levofolinate reconstituted in syringes and diluted in NaCl 0.9% and glucose 5% polyolefin/polyamide infusion bags. J Oncol Pharm Pract. 2021 Mar;27(2):288-296. doi: 10.1177/1078155220918025. Epub 2020 Apr 16. PMID: 32299315; PMCID: PMC7903855. 14: Mofidifar S, Sohraby F, Bagheri M, Aryapour H. Repurposing existing drugs for new AMPK activators as a strategy to extend lifespan: a computer-aided drug discovery study. Biogerontology. 2018 Apr;19(2):133-143. doi: 10.1007/s10522-018-9744-x. Epub 2018 Jan 15. PMID: 29335817. 15: Muto O, Munakata M, Yamagata K, Masuda A, Kotanagi K, Kichiraku T, Satoyoshi R, Kudoh K, Sawada T, Miyazawa H, Ouchi S, Kotanagi H, Sakata Y. Successful Treatment with 5-fluorouracil and Levofolinate Calcium in Advanced Gastric Cancer Patient with Disseminated Intravascular Coagulation. Gan To Kagaku Ryoho. 2017 Oct;44(10):867-869. PMID: 29066681. 16: Costa T, Nuñez J, Felismino T, Boente L, Mello C. REOX: Evaluation of the Efficacy of Retreatment With an Oxaliplatin-containing Regimen in Metastatic Colorectal Cancer: A Retrospective Single-center Study. Clin Colorectal Cancer. 2017 Dec;16(4):316-323. doi: 10.1016/j.clcc.2017.03.002. Epub 2017 Mar 16. PMID: 28392022. 17: Zhao R, Aluri S, Goldman ID. The proton-coupled folate transporter (PCFT- SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. Mol Aspects Med. 2017 Feb;53:57-72. doi: 10.1016/j.mam.2016.09.002. Epub 2016 Sep 21. PMID: 27664775; PMCID: PMC5253092. 18: Roselli M, Formica V, Cereda V, Jochems C, Richards J, Grenga I, Orlandi A, Ferroni P, Guadagni F, Schlom J. The association of clinical outcome and peripheral T-cell subsets in metastatic colorectal cancer patients receiving first-line FOLFIRI plus bevacizumab therapy. 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SRI22818

MedKoo CAT#: 558955

CAS#: 1429221-68-0