洛美曲索

生物活性靶点体外研究体内研究洛美曲索试剂级价格

洛美曲索

CAS号:106400-81-1
英文名:Lometrexol
中文名:洛美曲索
CBNumber:CB81179064
分子式:C21H25N5O6
分子量:443.45
MOL File:106400-81-1.mol

洛美曲索化学性质

密度 :1.56±0.1 g/cm3(Predicted)
储存条件 :2-8°C
溶解度 :DMSO: ≥5mg/mL
酸度系数(pKa) :3.60±0.10(Predicted)
形态 :powder
颜色 :white to light yellow
稳定性 :Hygroscopic

安全信息

危险品标志 :T
危险类别码 :25
安全说明 :45
危险品运输编号 :UN 2811 6.1 / PGIII
WGK Germany :3

洛美曲索性质、用途与生产工艺

生物活性 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，但不会引起可检测水平的 DNA 链断裂。Lometrexol hydrate 可以进一步抑制嘌呤从头合成，导致异常的细胞增殖，凋亡 (apoptosis) 和细胞周期停滞。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。
靶点

GARFT

体外研究

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).

Cell Viability Assay

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

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.

体内研究

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.

Animal Model:	C57BL/6 mice (7-8 week, 18-20 g)
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.