Lometrexol(Synonyms: DDATHF)

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Lometrexol (Synonyms: DDATHF)

Lometrexol (DDATHF) 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 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 具有抗癌活性。Lometrexol 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(Synonyms: DDATHF)

Lometrexol Chemical Structure

CAS No. : 106400-81-1

规格 价格 是否有货
10 mM * 1 mL in DMSO ￥8097 询问价格 & 货期
1 mg ￥2750 询问价格 & 货期
5 mg ￥8300 询问价格 & 货期
10 mg ￥13950 询问价格 & 货期

* Please select Quantity before adding items.

Lometrexol 的其他形式现货产品:

Lometrexol hydrate

生物活性

Lometrexol (DDATHF), an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) but do not induce detectable levels of DNA strand breaks. Lometrexol can further inhibit de novo purine synthesis, causing abnormal cell proliferation and apoptosis, even cell cycle arrest. Lometrexol has anticancer activity[1][2]. Lometrexol also is a potent human Serine hydroxymethyltransferase1/2 (hSHMT1/2) inhibitor[3].

IC50 & Target

GARFT[1]
体外研究
(In Vitro)

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

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究
(In Vivo)

Lometrexol (DDATHF; 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 (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[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

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.

Clinical Trial

分子量

443.45

Formula

C21H25N5O6
CAS 号

106400-81-1
中文名称

洛美曲索
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
溶解性数据
In Vitro: 

DMSO : ≥ 40 mg/mL (90.20 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.2550 mL 11.2752 mL 22.5505 mL
5 mM 0.4510 mL 2.2550 mL 4.5101 mL
10 mM 0.2255 mL 1.1275 mL 2.2550 mL

参考文献

  • [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.

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