[CAS NO. 106400-81-1] Lometrexol
PRODUCTS SPECIFICATIONS [106400-81-1]
DESCRIPTION [106400-81-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 443.45 |
| Molecular Formula | C21H25N5O6 |
| SMILES | O=C1C2=C(NC[C@H](CCC3=CC=C(C(N[C@@H](CCC(O)=O)C(O)=O)=O)C=C3)C2)N=C(N)N1 |
1 Publications Citing Use of MCE
Summary
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. Lometrexol also is a potent human Serine hydroxymethyltransferase1/2 ( hSHMT1/2 ) inhibitor [1] [2] [3] .
In Vitro
Lometrexol (DDATHF) binds tightly to GART, resulting in a rapid and prolonged depletion of intracellular purine ribonucleotides
[3]
.
Lometrexol (1-30 μM; 2-10 hours) induces rapid and complete growth inhibition in L1210 cells
[3]
.
Lometrexol (1 μM; 2-24 hours) induces cell cycle arrest in murine leukemia L1210 cells
[3]
.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [3]
| 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 [3]
| 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. |
In Vivo
Lometrexol (DDATHF; i.p.; 15-60 mg/kg; on gestation day 7.5) 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) 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) induces abnormal proliferation and
apoptosis
exist in neural tube defects (NTDs)
[1]
.
MedChemExpress (MCE) 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. |
| Animal Model: | C57BL/6 mice (7-8 week, 18-20 g) [1] |
| Dosage: | 40 mg/kg |
| Administration: | Intraperitoneal injection; on gestation day 7.5, for 0, 6, 24, 48 and 96 hours |
| Result: |
Inhibited glycinamide ribonucleotide formyl transferase (GARFT) activity and GARFT activity was maximally inhibited after at 6 hours.
Decreased the levels of ATP, GTP, dATP, and dGTP of NTDs embryonic brain tissue significantly at 6 hours. |
| Animal Model: | C57BL/6 mice (7-8 week, 18-20 g) [1] |
| Dosage: | 40 mg/kg |
| Administration: | Intraperitoneal injection; on gestation day 7.5, for 4 days |
| Result: | Decreased the expression of proliferation-related genes (Pcna, Foxg1 and Ptch1) and increased the expression of apoptosis-related genes (Bax, Casp8 and Casp9) in NTD groups. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00033722 | Tularik|National Cancer Institute (NCI) |
Lung Cancer
|
February 2002 | Phase 2 |
| NCT00024310 | Jonsson Comprehensive Cancer Center|National Cancer Institute (NCI) |
Drug+Agent Toxicity by Tissue+Organ|Unspecified Adult Solid Tumor, Protocol Specific
|
September 2001 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 225.50 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 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 |
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1.
Add each solvent one by one: 0.5% CMC-Na /saline water
Solubility: 25 mg/mL (56.38 mM); Suspended solution; Need ultrasonic
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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] 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.
- [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.