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Pralatrexate

现货
Catalog No.
A4350
抗叶酸,叶酸类似物。
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,820.00
现货
10mg
¥ 2,240.00
现货
50mg
¥ 6,790.00
现货

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Background

Pralatrexate is an inhibitor of DHFR with Ki value of 45 nM [1].

Dihydrofolate reductase (DHFR) is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, a methyl group shuttle required for the synthesis of purines, thymidylic acid, and certain amino acids.

Pralatrexate is a DHFR inhibitor with high affinity for folylpolyglutamate synthetase (FPGS) and reduced folate carrier 1 (RFC-1), resulting in extensive internalization and accumulation in tumour cells. In 15 human cancer cell lines, pralatrexate showed antiproliferative effects with IC50 < 0.1 μM in PC3, SCC61, DU145, HT29, HOP62, SQ20B, HOP92, HEP2 and IGROV1 cells. While it showed antiproliferative effects with IC50≥ 9 μM in Colo205, HCC2998, MCF7, HCT116, OVCAR3 and MDA-MB-435 cells [2].

In MV522 human non-small cell lung cancer (NSCLC) xenograft, pralatrexate showed increased antitumor activity. In the 2 mg/kg pralatrexate-treated group, the 38% tumor growth inhibition (TGI) was observed. In NCI-H460 NSCLC xenograft, pralatrexate showed antitumor activity in a dose-dependent way. TGI of 1 mg/kg and 2 mg/kg pralatrexate-treated groups was 34% and 52%, respectively. In the two xenografts, pralatrexate resulted in weight loss, which suggested its toxicity [1].

References:
[1].  Izbicka E, Diaz A, Streeper R, et al. Distinct mechanistic activity profile of pralatrexate in comparison to other antifolates in in vitro and in vivo models of human cancers. Cancer Chemother Pharmacol, 2009, 64(5): 993-999.
[2].  Serova M, Bieche I, Sablin MP, et al. Single agent and combination studies of pralatrexate and molecular correlates of sensitivity. Br J Cancer, 2011, 104(2): 272-280.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt477.47
Cas No.146464-95-1
FormulaC23H23N7O5
Solubility≥23.85 mg/mL in DMSO, <2.4 mg/mL in EtOH, <2.29 mg/mL in H2O
Chemical Name(2S)-2-[[4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl]amino]pentanedioic acid
SDFDownload SDF
Canonical SMILESC#CCC(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1,2]:

细胞系

癌细胞系,NCI-H460人NSCLC细胞,MV522人转移性NSCLC细胞

溶解方法

该化合物在DMSO中的溶解度大于23.9 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

72h

应用

Pralatrexate对15种癌细胞株显示出抗增殖活性,IC50值从对前列腺癌细胞系PC3的0.01 ± 0.002 μM,到对 MDA-MB-435细胞系的大于350 μM。Pralatrexate以剂量依赖性方式抑制DHFR的活性。在NCI-H460细胞中,Pralatrexate治疗15或60分钟导致放射性标记的抗叶酸剂的短期摄取。

动物实验 [1]:

动物模型

异种移植NCI-H460或MV522肿瘤细胞的雌性裸鼠

给药剂量

腹腔注射,1和2 mg/kg,每天×5,持续5天;两个周期

应用

在MV522人非小细胞肺癌(NSCLC)异种移植物中,pralatrexate显示出抗肿瘤活性。2 mg/kg的pralatrexate治疗组中观察到38%的肿瘤生长抑制(TGI)。在NCI-H460 NSCLC异种移植物中,pralatrexate以剂量依赖的方式显示抗肿瘤活性。1 mg/kg和2 mg/kg的pralatrexate治疗组的TGI分别为34%和52%。在NCI-H460和MV522人类肿瘤异种移植物中,pralatrexate以剂量依赖性方式造成体重减轻,说明其具有毒性作用。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Izbicka E, Diaz A, Streeper R, et al. Distinct mechanistic activity profile of pralatrexate in comparison to other antifolates in in vitro and in vivo models of human cancers[J]. Cancer chemotherapy and pharmacology, 2009, 64(5): 993-999.

[2]. Serova M, Bieche I, Sablin M P, et al. Single agent and combination studies of pralatrexate and molecular correlates of sensitivity[J]. British journal of cancer, 2011, 104(2): 272.

质量控制

质量控制和MSDS

批次:

化学结构

Pralatrexate