Lometrexol hydrate  (Synonyms: DDATHF hydrate)

Lometrexol (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^[1][2][3].

Lometrexol (DDATHF) hydrate binds tightly to GART, resulting in a rapid and prolonged depletion of intracellular purine ribonucleotides^[3].
Lometrexol (1-30 μM; 2-10 hours) hydrate induces rapid and complete growth inhibition in L1210 cells^[3].
Lometrexol (1 μM; 2-24 hours) hydrate induces cell cycle arrest in murine leukemia L1210 cells^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Lometrexol (DDATHF; i.p.; 15-60 mg/kg; on gestation day 7.5) hydrate induces neural tube defects (NTDs) by disturbing purine metabolism and increases the rate of embryonic resorption and growth retardation in a dose-dependent manner^[1].
Lometrexol (i.p.; 40 mg/kg; on gestation day 7.5) hydrate decreases glycinamide ribonucleotide formyl transferase (GARFT) activity and Changes of ATP, GTP, dATP and dGTP levels^[1].
Lometrexol (i.p.; 40 mg/kg; on gestation day 7.5) hydrate induces abnormal proliferation and apoptosis exist in neural tube defects (NTDs)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

461.47

Solid

C₂₁H₂₇N₅O₇

1435784-14-7

O=C(O)CC[[email protected]@H](C(O)=O)NC(C1=CC=C(CC[[email protected]@H](CN2)CC3=C2N=C(N)NC3=O)C=C1)=O.O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [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.  [Content Brief]

  [2]. Scaletti E, et, al. Structural basis of inhibition of the human serine hydroxymethyltransferase SHMT2 by antifolate drugs. FEBS Lett. 2019 Jul;593(14):1863-1873.  [Content Brief]

  [3]. Bronder JL, 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.  [Content Brief]