| CAS |
No.137281-23-3 |
| 中文名称 |
培美曲塞酸 |
| 英文名称 |
Pemetrexed |
| 别名 |
培美曲塞 |
| 分子式 |
C20H21N5O6 |
| 分子量 |
427.41 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
HPLC≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| EC |
EINECS 680-625-9 |
| MDL |
MFCD19105065 |
| SMILES |
O=C1NC(N)=NC2=C1C(CCC3=CC=C(C(N[C@H](C(O)=O)CCC(O)=O)=O)C=C3)=CN2 |
| InChIKey |
WBXPDJSOTKVWSJ-ZDUSSCGKSA-N |
| InChI |
InChI=1S/C20H21N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/t13-/m0/s1 |
| PubChem CID |
135410875 |
| 靶点 |
Antifolate |
| 通路 |
Cell Cycle;DNA Damage/DNA Repair;Metabolic Enzyme&Protease |
| 背景说明 |
Pemetrexed是一种叶酸拮抗剂，可结合并抑制胸苷酸合成酶 (TS),二氢叶酸还原酶 (DHFR) 和甘氨酰胺核苷酸甲酰转移酶 (GARFT)。 |
| 生物活性 |
Pemetrexed (LY231514) is an antifolate， the Ki values of the pentaglutamate of Pemetrexed (LY231514) are 1.3， 7.2， and 65 nM for inhibits thymidylate synthase (TS)， dihydrofolate reductase (DHFR)， and glycinamide ribonucleotide formyltransferase (GARFT)， respectively.[1-2] |
| IC50 |
Ki: 1.3 nM (TS)， 7.2 nM (DHFR)， 65 nM (GARFT)[1] |
| In Vitro |
Pemetrexed (LY231514) disodium is a novel classical antifolate， the antitumor activity of which may result from simultaneous and multipie inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. Pemetrexed (LY231514) is one of the best substrates that is known for the enzyme FPGS (Km=1.6 μM and Vmax/Km=621). It is likely that polyglutamation and the polyglutamated metabolites of LY231514 play profound roles in determining both the selectivity and the antitumor activity of this novel agent. Whereas LY23l5l4 only moderately inhibits TS (Ki=340 nM， recombinant mouse)， the pentaglutamate of LY23l5l4 is 100-fold more potent (Ki=3.4 nM)， making LY231514 one of the most potent folate-based TS inhibitors[1]. |
| In Vivo |
The group of mice treated with PC61 plus Pemetrexed demonstrates statistically longer survival than other groups. In a survival analysis， significantly better survival is observed in the group of mice treated with PC61 plus Pemetrexed compare with those treated with PC61 alone， rat IgG plus Pemetrexed， or no treatment[2]. |
| 细胞实验 |
Dose-response curves are generated to determine the concentration required for 50% inhibition of growth (IC50). Pemetrexed is dissolved initially in DMSO at a concentration of 4 mg/mL and further diluted with cell culture medium to the desired concentration. CCRF-CEM leukemia cells in complete medium are added to 24-well Cluster plates at a final concentration of 4.8×104 cells/well in a total volume of 2 mL. Test compounds at various concentrations are added to duplicate wells so that the final volume of DMSO is 0.5%. The plates are incubated for 72 h at 37°C in an atmosphere of 5% CO2 in air. At the end of the incubation， cell numbers are determined on a ZBI Coulter counter. Control wells usually contain 4×105 to 6×105 cells at the end of the incubation. For several studies， IC50s are determined for each compound in the presence of either 300 μM AICA， 5 μM thymidine， 100 μM hypoxanthine， or combination of 5 μM hymidine plus 100 μM hypoxanthine[1]. |
| 动物实验 |
Mice[2] Female CBA mice and female NOD/SCID mice (NOD.CB17-Prkdcscid) at 6-8 wk of age are used. Premetrexed (100 mg/kg) is given i.p. from days 4-8 (5 consecutive d) to tumor-bearing mice to explore the synergistic effect when combined with anti-CD25 Ab or IgG control. The dose and schedule used for Pemetrexed in the current study is determined based on previous studies in mice. |
| 激酶实验 |
AICARFT inhibition assays are carried out at room temperature by monitoring the formation of [6S]-5，6，7，8-tetrahydrofolate from 10-formyl-[6R，S]-5，6，7，8-tetrahydrofolate at A298. All solutions are purged with N2 gas prior to use. The reaction solution contains 33 mM Tris-Cl， pH 7.4， 25 mM KCl， 5 mM 2-Mercaptoethanol， 0.05 mM AICA ribonucleotide， and 16 nM (2 milliunits/mL) of AICARFT. 10-Formyl-[6R，S]-5，6，7，8-tetrahydrofolate concentrations of 0.037， 0.074， and 0.145 mM are used (0.61， 1.23， and 2.45 times its Km value， respectively). LY231514 is tested as an inhibitor at 0.08-0.8 mM (four concentrations). When the tri- and pentaglutamates of LY231514 are used as inhibitors， the concentrations are 0.0005-0.009 mM (eight concentrations). Enzyme assays are initiated by the addition of enzyme. Data is analyzed using the ENZFITTER program for competitive inhibition.[1] |
| 数据来源文献 |
[1]. Shih C， et al. LY231514， a pyrrolo[2，3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res. 1997 Mar 15;57(6):1116-23.
[2]. Anraku M， et al. Synergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignantmesothelioma. J Immunol. 2010 Jul 15;185(2):956-66. |
| 规格 |
50mg 100mg |
| 单位 |
瓶 |
中文
英语
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