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MedKoo Cat#: 599172 | Name: Lometrexol hydrate
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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 hydrate
Lometrexol hydrate
CAS#1435784-14-7 (hydrate)

Theoretical Analysis

MedKoo Cat#: 599172

Name: Lometrexol hydrate

CAS#: 1435784-14-7 (hydrate)

Chemical Formula: C21H27N5O7

Exact Mass: 443.1805

Molecular Weight: 461.48

Elemental Analysis: C, 54.66; H, 5.90; N, 15.18; O, 24.27

Price and Availability

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5mg USD 450.00 2 Weeks
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Related CAS #
120408-07-3 (sodium) 106400-81-1 (free acid) 1435784-14-7 (hydrate) 124511-17-7 (camsylate) 95693-76-8 (free acid)
Synonym
Lometrexol; DDATHF; DATHF; LY 264618 hydrate; LY-264618; LY264618;
IUPAC/Chemical Name
(4-(2-(2-amino-4-oxo-1,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl)ethyl)benzoyl)-L-glutamic acid hydrate
InChi Key
AEFQSKJUVDZANQ-GNFRJPFZSA-N
InChi Code
InChI=1S/C21H25N5O6.H2O/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);1H2/t12?,15-;/m0./s1
SMILES Code
O=C(O)CC[C@@H](C(O)=O)NC(C1=CC=C(CCC(CN2)CC3=C2NC(N)=NC3=O)C=C1)=O.[H]O[H]
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
>3 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
2934.99.03.00
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Lometrexol (DDATHF) hydrate, an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT).
In vitro activity:
Here, this shows that the antifolates lometrexol and pemetrexed are inhibitors of SHMT2 and solve the first SHMT2-antifolate structures. Lometrexol was found to be the best hSHMT1/2 inhibitor from a panel antifolates. Reference: FEBS Lett. 2019 Jul;593(14):1863-1873. https://pubmed.ncbi.nlm.nih.gov/31127856/
In vivo activity:
40 mg kg(-1) body weight (b/w) of DDATHF caused the highest incidence of NTDs (30.8 %) and therefore was selected as the optimal dose to establish murine NTDs. The GARFT activity and levels of ATP, GTP, dATP and dGTP in embryonic brain tissue were significantly decreased after DDATHF treatment. Reference: Nutr Metab (Lond). 2016 Aug 23;13(1):56. https://pubmed.ncbi.nlm.nih.gov/27555878/
Solvent mg/mL mM
Solubility
DMSO 40.0 86.68
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 461.48 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. 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. 2. 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. 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. 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. 2. 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.
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.
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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.