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MedKoo Cat#: 205977 | Name: Lometrexol disodium
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Description:

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

Lometrexol, also known as LY264618, is a folate analog antimetabolite with antineoplastic activity. As the 6R diastereomer of 5,10-dideazatetrahydrofolate, lometrexol inhibits glycinamide ribonucleotide formyltransferase (GARFT), the enzyme that catalyzes the first step in the de novo purine biosynthetic pathway, thereby inhibiting DNA synthesis, arresting cells in the S phase of the cell cycle, and inhibiting tumor cell proliferation. The agent has been shown to be active against tumors that are resistant to the folate antagonist methotrexate.

Chemical Structure

Lometrexol disodium
Lometrexol disodium
CAS#120408-07-3 (sodium)

Theoretical Analysis

MedKoo Cat#: 205977

Name: Lometrexol disodium

CAS#: 120408-07-3 (sodium)

Chemical Formula: C21H23N5Na2O6

Exact Mass: 0.0000

Molecular Weight: 487.42

Elemental Analysis: C, 51.75; H, 4.76; N, 14.37; Na, 9.43; O, 19.69

Price and Availability

Size Price Availability Quantity
5mg USD 190.00 Ready to ship
10mg USD 350.00 Ready to ship
25mg USD 550.00 Ready to ship
50mg USD 950.00 Ready to ship
100mg USD 1,650.00 Ready to ship
200mg USD 2,950.00 Ready to ship
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Related CAS #
120408-07-3 (sodium) 106400-81-1 (free acid) 1435784-14-7 (hydrate) 124511-17-7 (camsylate)
Synonym
LY 264618; LY-264618; LY264618; NSC722969; NSC-722969; NSC-722969. (6R)DDATHF; LMTX; DDATHF disodium; Lometrexol sodium; Lometrexol.
IUPAC/Chemical Name
Disodium (4-(2-((R)-2-amino-4-oxo-1,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl)ethyl)benzoyl)-L-glutamate
InChi Key
SVJSWELRJWVPQD-KJWOGLQMSA-L
InChi Code
InChI=1S/C21H25N5O6.2Na/c22-21-25-17-14(19(30)26-21)9-12(10-23-17)2-1-11-3-5-13(6-4-11)18(29)24-15(20(31)32)7-8-16(27)28;;/h3-6,12,15H,1-2,7-10H2,(H,24,29)(H,27,28)(H,31,32)(H4,22,23,25,26,30);;/q;2*+1/p-2/t12-,15+;;/m1../s1
SMILES Code
O=C(O[Na])[C@@H](NC(C1=CC=C(CC[C@@H](CN2)CC3=C2NC(N)=NC3=O)C=C1)=O)CCC(O[Na])=O
Appearance
White to off-white 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, soluble in water.
Shelf Life
>5 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
 Related CAS#: 120408-07-3 (Lometrexol disodium); 106400-81-1 (Lometrexol) Lometrexol free acid: Chemical Formula: C21H25N5O6 Exact Mass: 443.1805 Molecular Weight: 443.4600 Elemental Analysis: C, 56.88; H, 5.68; N, 15.79; O, 21.65      
Biological target:
Lometrexol, also known as LY264618, is a folate analog antimetabolite with antineoplastic activity that inhibits glycinamide ribonucleotide formyltransferase (GARFT).
In vitro activity:
The cytotoxicity activity of DDATHF was evaluated in vitro in NIH/3T3 cells transfected with human alpha-folate-binding protein (FBP) complementary DNA to examine the role of the receptor. In FBP-transfected NIH/3T3 (FBP-tNIH/3T3) cells, which internalised about three times more 5-methyltetrahydrofolic acid than the mock-transfected cells, the cytotoxtic potential of DDATHF showed a clear increase. Subsequently, we analysed four ovarian carcinoma cell lines (OVCAR3, IGROV1, SKOV3, and SW626) expressing different amounts of FBP. a medium containing 2.27 microM folic acid the DDATHF IC50 values were 50 nm on OVCAR3, 500 nM on SW626 and 1000 nM on IGROV1. In folic acid-free medium IC50 values were 2 nM on OVCAR3 and Sw626 and 40 nM on IGROV1. On SKOV3 cells DDATHF cytotoxicity was the same regardless of the amount of folic acid in the medium (IC50 8 nM). Reference: Br J Cancer. 1996 Feb;73(4):525-30. https://pubmed.ncbi.nlm.nih.gov/8595169/
In vivo activity:
This study aims to induce murine NTDs by inhibiting one of the folate metabolic pathways, de novo purine synthesis and preliminarily investigate the potential mechanisms. The key enzyme, glycinamide ribonucleotide formyl transferase (GARFT) was inhibited by a specific inhibitor, lometrexol (DDATHF) in the pregnant mice. Pregnant mice were intraperitoneally injected with various doses of DDATHF on gestational day 7.5 and embryos were examined for the presence of NTDs on gestational day 11.5. GARFT activity in embryonic tissue of control and DDATHF treated was detected at 0, 6, 24, 48 and 96 h after i.p. injection of optimal DDATHF dose on gestational day 7.5 to confirm the effects of DDATHF on de novo purine synthesis. Compared with the control embryo, GARFT activity was maximally inhibited after at 6 h after DDATHF injection, and thereafter gradually increased with time but remained significantly lower than control even at 96 h. (Fig. 2a). The result showed that GARFT activity was inhibited by DDATHF. ATP, GTP, dATP and dGTP levels were measured using high performance liquid chromatography following DDATHF treatment at 0, 6, 24, 48 and 96 h, respectively. Compared to control, levels of ATP, GTP, dATP and dGTP of NTDs embryonic brain tissue decreased significantly at 6 h after DDATHF treatment, and more significantly over time (Fig. 3).Furthermore, Levels of proliferation-related genes (Pcna, Foxg1 and Ptch1) were downregulated and apoptosis-related genes (Bax, Casp8 and Casp9) were upregulated. Expression of phosphohistone H3 was significantly decreased while expression of cleaved caspase-3 was greatly increased. Results indicate that DDATHF induced murine NTDs by disturbing purine metabolism and further led to abnormal proliferation and apoptosis. Reference: Nutr Metab (Lond). 2016; 13(1): 56. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994272/
Solvent mg/mL mM
Solubility
DMSO 0.0 0.00
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 487.42 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.

Recalculate based on batch purity %
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. Erba E, Sen S, Sessa C, Vikhanskaya FL, D'Incalci M. Mechanism of cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cells in vitro and modulation of the drug activity by folic or folinic acid. Br J Cancer. 1994 Feb;69(2):205-11. doi: 10.1038/bjc.1994.40. PMID: 8297715; PMCID: PMC1968679. 2. Sen S, Erba E, D'Incalci M, Bottero F, Canevari S, Tomassetti A. Role of membrane folate-binding protein in the cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cell lines in vitro. Br J Cancer. 1996 Feb;73(4):525-30. doi: 10.1038/bjc.1996.91. PMID: 8595169; PMCID: PMC2074460. 3. Xu L, Wang L, Wang J, Zhu Z, Chang G, Guo Y, Tian X, Niu B. The effect of inhibiting glycinamide ribonucleotide formyl transferase on the development of neural tube in mice. Nutr Metab (Lond). 2016 Aug 23;13(1):56. doi: 10.1186/s12986-016-0114-x. PMID: 27555878; PMCID: PMC4994272.
In vitro protocol:
1. Erba E, Sen S, Sessa C, Vikhanskaya FL, D'Incalci M. Mechanism of cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cells in vitro and modulation of the drug activity by folic or folinic acid. Br J Cancer. 1994 Feb;69(2):205-11. doi: 10.1038/bjc.1994.40. PMID: 8297715; PMCID: PMC1968679. 2. Sen S, Erba E, D'Incalci M, Bottero F, Canevari S, Tomassetti A. Role of membrane folate-binding protein in the cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cell lines in vitro. Br J Cancer. 1996 Feb;73(4):525-30. doi: 10.1038/bjc.1996.91. PMID: 8595169; PMCID: PMC2074460.
In vivo protocol:
1. Xu L, Wang L, Wang J, Zhu Z, Chang G, Guo Y, Tian X, Niu B. The effect of inhibiting glycinamide ribonucleotide formyl transferase on the development of neural tube in mice. Nutr Metab (Lond). 2016 Aug 23;13(1):56. doi: 10.1186/s12986-016-0114-x. PMID: 27555878; PMCID: PMC4994272.
1: Li T, Song L, Zhang Y, Han Y, Zhan Z, Xv Z, Li Y, Tang Y, Yang Y, Wang S, Li S, Zheng L, Li Y, Gao Y. Molecular mechanism of c-Myc and PRPS1/2 against thiopurine resistance in Burkitt's lymphoma. J Cell Mol Med. 2020 Jun;24(12):6704-6715. doi: 10.1111/jcmm.15322. Epub 2020 May 11. PMID: 32391636; PMCID: PMC7299692. 2: Scaletti E, Jemth AS, Helleday T, Stenmark P. Structural basis of inhibition of the human serine hydroxymethyltransferase SHMT2 by antifolate drugs. FEBS Lett. 2019 Jul;593(14):1863-1873. doi: 10.1002/1873-3468.13455. Epub 2019 Jun 10. PMID: 31127856. 3: Xu L, Wang L, Wang J, Zhu Z, Chang G, Guo Y, Tian X, Niu B. The effect of inhibiting glycinamide ribonucleotide formyl transferase on the development of neural tube in mice. Nutr Metab (Lond). 2016 Aug 23;13(1):56. doi: 10.1186/s12986-016-0114-x. PMID: 27555878; PMCID: PMC4994272. 4: Fekry B, Esmaeilniakooshkghazi A, Krupenko SA, Krupenko NI. Ceramide Synthase 6 Is a Novel Target of Methotrexate Mediating Its Antiproliferative Effect in a p53-Dependent Manner. PLoS One. 2016 Jan 19;11(1):e0146618. doi: 10.1371/journal.pone.0146618. PMID: 26783755; PMCID: PMC4718595. 5: Li B, Li H, Bai Y, Kirschner-Schwabe R, Yang JJ, Chen Y, Lu G, Tzoneva G, Ma X, Wu T, Li W, Lu H, Ding L, Liang H, Huang X, Yang M, Jin L, Kang H, Chen S, Du A, Shen S, Ding J, Chen H, Chen J, von Stackelberg A, Gu L, Zhang J, Ferrando A, Tang J, Wang S, Zhou BB. Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL. Nat Med. 2015 Jun;21(6):563-71. doi: 10.1038/nm.3840. Epub 2015 May 11. PMID: 25962120; PMCID: PMC4670083. 6: Paiardini A, Fiascarelli A, Rinaldo S, Daidone F, Giardina G, Koes DR, Parroni A, Montini G, Marani M, Paone A, McDermott LA, Contestabile R, Cutruzzolà F. Screening and in vitro testing of antifolate inhibitors of human cytosolic serine hydroxymethyltransferase. ChemMedChem. 2015 Mar;10(3):490-7. doi: 10.1002/cmdc.201500028. Epub 2015 Feb 10. PMID: 25677305; PMCID: PMC5438088. 7: Tomsho JW, Moran RG, Coward JK. Concentration-dependent processivity of multiple glutamate ligations catalyzed by folylpoly-gamma-glutamate synthetase. Biochemistry. 2008 Aug 26;47(34):9040-50. doi: 10.1021/bi800406w. Epub 2008 Aug 2. PMID: 18672898; PMCID: PMC2805413. 8: Qi H, Ratnam M. Synergistic induction of folate receptor beta by all-trans retinoic acid and histone deacetylase inhibitors in acute myelogenous leukemia cells: mechanism and utility in enhancing selective growth inhibition by antifolates. Cancer Res. 2006 Jun 1;66(11):5875-82. doi: 10.1158/0008-5472.CAN-05-4048. PMID: 16740727. 9: Tomsho JW, McGuire JJ, Coward JK. Synthesis of (6R)- and (6S)-5,10-dideazatetrahydrofolate oligo-gamma-glutamates: kinetics of multiple glutamate ligations catalyzed by folylpoly-gamma-glutamate synthetase. Org Biomol Chem. 2005 Sep 21;3(18):3388-98. doi: 10.1039/b505907k. Epub 2005 Aug 15. Erratum in: Org Biomol Chem. 2005 Oct 21;3(20):3825. PMID: 16132101; PMCID: PMC1989673. 10: Cheng H, Chong Y, Hwang I, Tavassoli A, Zhang Y, Wilson IA, Benkovic SJ, Boger DL. Design, synthesis, and biological evaluation of 10-methanesulfonyl- DDACTHF, 10-methanesulfonyl-5-DACTHF, and 10-methylthio-DDACTHF as potent inhibitors of GAR Tfase and the de novo purine biosynthetic pathway. Bioorg Med Chem. 2005 May 16;13(10):3577-85. doi: 10.1016/j.bmc.2004.12.004. PMID: 15848770. 11: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Oct;26(8):639-63. PMID: 15605126. 12: Dumez H, Reinhart WH, Guetens G, de Bruijn EA. Human red blood cells: rheological aspects, uptake, and release of cytotoxic drugs. Crit Rev Clin Lab Sci. 2004;41(2):159-88. doi: 10.1080/10408360490452031. PMID: 15270553. 13: Theti DS, Jackman AL. The role of alpha-folate receptor-mediated transport in the antitumor activity of antifolate drugs. Clin Cancer Res. 2004 Feb 1;10(3):1080-9. doi: 10.1158/1078-0432.ccr-03-0157. PMID: 14871988. 14: Kamal MA, Christopherson RI. Accumulation of 5-phosphoribosyl-1-pyrophosphate in human CCRF-CEM leukaemia cells treated with antifolates. Int J Biochem Cell Biol. 2004 Mar;36(3):545-51. doi: 10.1016/j.biocel.2003.08.014. Erratum in: Int J Biochem Cell Biol. 2004 May;36(5):957. PMID: 14687931. 15: Bronder JL, Moran RG. A defect in the p53 response pathway induced by de novo purine synthesis inhibition. J Biol Chem. 2003 Dec 5;278(49):48861-71. doi: 10.1074/jbc.M304844200. Epub 2003 Sep 29. PMID: 14517211. 16: Zhang Y, Desharnais J, Marsilje TH, Li C, Hedrick MP, Gooljarsingh LT, Tavassoli A, Benkovic SJ, Olson AJ, Boger DL, Wilson IA. Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid. Biochemistry. 2003 May 27;42(20):6043-56. doi: 10.1021/bi034219c. PMID: 12755606. 17: Purcell WT, Ettinger DS. Novel antifolate drugs. Curr Oncol Rep. 2003 Mar;5(2):114-25. doi: 10.1007/s11912-003-0098-3. PMID: 12583828. 18: Bronder JL, Moran RG. Antifolates targeting purine synthesis allow entry of tumor cells into S phase regardless of p53 function. Cancer Res. 2002 Sep 15;62(18):5236-41. PMID: 12234990. 19: Mauritz R, Peters GJ, Priest DG, Assaraf YG, Drori S, Kathmann I, Noordhuis P, Bunni MA, Rosowsky A, Schornagel JH, Pinedo HM, Jansen G. Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis. Biochem Pharmacol. 2002 Jan 15;63(2):105-15. doi: 10.1016/s0006-2952(01)00824-3. PMID: 11841783. 20: Rivory LP, Clarke SJ, Boyer M, Bishop JF. Highly sensitive analysis of the antifolate pemetrexed sodium, a new cancer agent, in human plasma and urine by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 2001 Dec 25;765(2):135-40. doi: 10.1016/s0378-4347(01)00406-6. PMID: 11767306.