Pemetrexed
Pemetrexed (also known as pemetrexed disodium) is a novel antifolate antimetabolite targeting multiple enzymes involved in both pyrimidine and purine synthesis. Pemetrexed is an analog of the classic antifolate GARFYT inhibitor lometroxol with a similar chemical structure, where the pyrazine ring in the pterine portion of folic acid and the benzylic nitrogen in the bridge portion of folic acid are replaced by a pyrrole ring and a methylene group respectively. Pemetrexed potently inhibits TS, DHFR, and GARFT as well as AICARFT but with a lesser potency and exhibits autitumor activity in a broad range of tumors, including non-small cell lung carcinoma, malignant mesothelioma, and carcinomas of the breast, colorectum, uterine cervix, head and neck, and bladder.
Reference
Luis Paz-Ares, Susana Bezares, Jose M. Tabernero, Daniel Castellanos, and Hernan Cortes-Funes. Review of a promising new agent-pemetrexed disodium. Cancer 2003; 97(8 Suppl):2056-2063
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 471.37 |
| Cas No. | 150399-23-8 |
| Formula | C20H19N5Na2O6 |
| Synonyms | Pemetrexed disodium, LY-231514, Pemetrexed Na |
| Solubility | insoluble in EtOH; ≥15.68 mg/mL in DMSO with gentle warming and ultrasonic; ≥30.67 mg/mL in H2O |
| Chemical Name | disodium;(2S)-2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate |
| SDF | Download SDF |
| Canonical SMILES | C1=CC(=CC=C1CCC2=CNC3=C2C(=O)N=C(N3)N)C(=O)NC(CCC(=O)[O-])C(=O)[O-].[Na+].[Na+] |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
Human tumor cell lines, including CCRF-CEM leukemia, GC3/C1 colon carcinoma, and HCT-8 ileocecal carcinoma |
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Reaction Conditions |
0.0001 ~ 30 μM pemetrexed for 72 h incubation |
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Applications |
Pemetrexed exerted antiproliferative activity in all three cell lines. Thymidine (5 μM) only increased the IC50 of pemetrexed versus CCRF-CEM cells by 5.5-fold, GC3/C1 by 18.7-fold, and HCT-8 by 15-fold. Higher drug concentrations of pemetrexed required the combination of thymidine and hypoxanthine to protect these cells. |
| Animal experiment:[2] | |
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Animal models |
An intrathoracic murine model of malignant mesothelioma |
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Dosage form |
100 mg/kg Administered intraperitoneally from days 4 ~ 8 |
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Applications |
The combination of pemetrexed and regulatory T cell (Treg) blockade showed synergistic antitumor effects in murine malignant mesothelioma, resulting in prolonged survival. This combination was associated with decreased tumor-infiltrating Tregs, increased IL-2 production, dendritic cell maturation, and increased CD3+CD8+IFN-γ+ tumor-infiltrating T cells when compared with mice treated with pemetrexed alone or Treg blockade alone. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Shih C, Chen VJ, Gossett LS, et al. LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Research, 1997, 57(6): 1116-1123. 2. Anraku M, Tagawa T, Wu L, et al. Synergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignant mesothelioma. Journal of Immunology, 2010, 185(2):956-966. |
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| Description | Pemetrexed is a novel antifolate and antimetabolite for TS, DHFR and GARFT with Ki of 1.3 nM, 7.2 nM and 65 nM, respectively. | |||||
| Targets | TS | DHFR | GARFT | |||
| IC50 | 1.3 nM (Ki) | 7.2 nM (Ki) | 65 nM (Ki) | |||
Quality Control & MSDS
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Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
