Lometrexol hydrate

Lometrexol hydrate (DDATHF hydrate), an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) but do not induce detectable levels of DNA strand breaks. Lometrexol hydrate can further inhibit de novo purine synthesis, causing abnormal cell proliferation and apoptosis, even cell cycle arrest. Lometrexol hydrate has anticancer activity. Lometrexol hydrate also is a potent human Serine hydroxymethyltransferase1/2 (hSHMT1/2) inhibitor.

Product information

CAS Number: 1435784-14-7

Molecular Weight: 461.47

Formula: C21H27N5O7

Synonym:

DDATHF hydrate

Chemical Name: (2S)-2-[(4-{2-[(6R)-2-amino-4-oxo-3H, 4H, 5H, 6H, 7H, 8H-pyrido[2, 3-d]pyrimidin-6-yl]ethyl}phenyl)formamido]pentanedioic acid hydrate

Smiles: O.NC1NC(=O)C2C[C@H](CNC=2N=1)CCC1C=CC(=CC=1)C(=O)N[C@@H](CCC(O)=O)C(O)=O

InChiKey: AEFQSKJUVDZANQ-YLCXCWDSSA-N

InChi: 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+;/m1./s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 40 mg/mL (86.68 mM; Need ultrasonic and warming)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Lometrexol hydrate (DDATHF hydrate) binds tightly to GART, resulting in a rapid and prolonged depletion of intracellular purine ribonucleotides. Lometrexol hydrate (1-30 μM; 2-10 hours) induces rapid and complete growth inhibition in L1210 cells. Lometrexol hydrate (1 μM; 2-24 hours) induces cell cycle arrest in murine leukemia L1210 cells. Lometrexol hydrate induces abnormal proliferation and apoptosis exist in neural tube defects (NTDs).

In Vivo:

Lometrexol hydrate (DDATHF hydrate; i.p.; 15-60 mg/kg; on gestation day 7.5) increases the rate of embryonic resorption and growth retardation in a dose-dependent manner. Lometrexol hydrate (i.p.; 40 mg/kg) maximally inhibits GARFT activity after at 6 hours and thereafter gradually increases with time but remains significantly lower than control even at 96 hours. Levels of ATP, GTP, dATP and dGTP of NTDs embryonic brain tissue decreases significantly at 6 h, and more significantly over time.

References:

1. Xu L, et al. 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.
2. Julie L Bronder, et al. 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.
3. Emma Scaletti, et al. Structural basis of inhibition of the human serine hydroxymethyltransferase SHMT2 by antifolate drugs. FEBS Lett. 2019 Jul;593(14):1863-1873.

Products are for research use only. Not for human use.