Lometrexol hydrate (DDATHF hydrate) 是一种抗嘌呤类抗叶酸 (Antifolate) 药，可抑制甘氨酰胺核糖核苷酸甲酰基转移酶 (GARFT) 的活性，但不会诱导可检测水平的 DNA 链断裂。Lometrexol hydrate 可以进一步抑制嘌呤从头合成，引起异常的细胞增殖和凋亡，甚至细胞周期停滞。Lometrexol hydrate 具有抗癌活性。Lometrexol hydrate 还是一种有效的人丝氨酸羟甲基转移酶 1/2 (hSHMT1/2) 抑制剂。

Lometrexol hydrate (DDATHF hydrate) is an antipurine antifolate which inhibits 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 [1] [2]. Lometrexol hydrate also is a potent human Serine hydroxymethyltransferase1/2 (h SHMT1/2 ) inhibitor [3].

Lometrexol hydrate (DDATHF hydrate) binds tightly to GART, causing a rapid and prolonged depletion of intracellular purine ribonucleotides [2]. Lometrexol hydrate (1-30 μM; 2-10 hours) induces rapid and complete growth inhibition in L1210 cells [2]. Lometrexol hydrate (1 μM; 2-24 hours) induces cell cycle arrest in murine leukemia L1210 cells [2]. Lometrexol hydrate induces abnormal proliferation and apoptosis exist in neural tube defects (NTDs) [1]. Cell Viability Assay [2] Cell Line: Mouse leukemia L1210 cells Concentration: 1, 30 μM Incubation Time: 2, 4, 6, 8, 10 hours Result: Induced rapid and complete growth inhibition. Cell Cycle Analysis [2] Cell Line: L1210 cells Concentration: 1 μM Incubation Time: 2, 4, 8, 12, 24 hours Result: Caused a rapid loss of the G2/M phase population of cells and an early S phase accumulation of cells by 8 hours. By 24 h, the S phase population appeared to be slowly shifting to higher DNA content, and hence, from mid-to-late S phase.

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 [1]. Lometrexol hydrate (i.p.; 40 mg/kg) maximally inhibits GARFT activity after at 6 hours and thereafter gradually increases over 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 [1]. Animal Model: C57BL/6 mice (7-8 week, 18-20 g) [1] Dosage: 15, 30, 35, 40, 45 and 60 mg/kg Administration: Intraperitoneal injection; on gestation day 7.5 Result: Increased the rate of embryonic resorption and growth retardation in a dose-dependent manner.

1435784-14-7

C21H27N5O7

461.47

Lometrexol hydrate

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years