Home>>Signaling Pathways>> Microbiology & Virology>> Parasite>>LXE408

LXE408 Sale

目录号 : GC64282

LXE408 是一种口服有效的,非竞争性的,动素体选择性蛋白酶体 (proteasome) 抑制剂。LXE408 抑制 L. donovani 蛋白酶体 (IC50=0.04 μM) 和 L. donovani (EC50=0.04 μM)。LXE408 具有较弱的透过血脑屏障能力。LXE408 具有用于内脏利什曼病 (VL) 研究的潜力。

LXE408 Chemical Structure

Cas No.:1799330-15-6

规格 价格 库存 购买数量
5 mg
¥6,210.00
现货
10 mg
¥10,350.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

产品描述

LXE408 is an orally active, non-competitive and kinetoplastid-selective proteasome inhibitor. LXE408 has an IC50 of 0.04 μM for L. donovani proteasome and an EC50 of 0.04 μM for L. donovani. LXE408 has a low propensity to cross the blood brain barrier. LXE408 has the potential for visceral leishmaniasis (VL) research[1].

LXE408 (compound 1) can occupy the pocket as a ternary complex with the proteasome. LXE408 shows no inhibition of the hERG channel (IC50>30 μM) in a manual patch clamp assay. LXE408 has a low propensity to cross the blood brain barrier (brain/plasma AUC ratio=0.03 in mice)[1].

LXE408 (compound 1; 0.3-10 mg/kg; PO; twice daily for 8 days) potently reduces the parasite burden in the liver in a dose-dependent manner[1]. LXE408 (1, 3, 10, 20 mg/kg; p.o.; b.i.d.; for 10 days) effects robust healing of parasite-induced skin lesions at the base of the tail in BALB/c mice infected with L. major[1]. LXE408 (5 mg/kg IV and 20 mg/kg PO) has a T1/2 of 3.3 hours for mouse. LXE408 (3 mg/kg IV and 10 mg/kg PO) has a T1/2 of 3.8 hours, a CL of 2.1 mL/min•kg, and a Vss of 0.53 L/kg for male Sprague-Dawley rat[1]. LXE408 (0.3 mg/kg IV and 1.0 mg/kg PO) has a T1/2 of 3.8 hours for male beagle dog. LXE408 (0.3 mg/kg IV and 10 mg/kg PO) has a T1/2 of 9.7 hours for male cynomolgus monkey[1].

[1]. Advait Nagle, et al. Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases. J Med Chem. 2020 Jul 15.

Chemical Properties

Cas No. 1799330-15-6 SDF Download SDF
分子式 C23H18FN7O2 分子量 443.43
溶解度 储存条件 Store at -20°C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 2.2551 mL 11.2757 mL 22.5515 mL
5 mM 0.451 mL 2.2551 mL 4.5103 mL
10 mM 0.2255 mL 1.1276 mL 2.2551 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置

Research Update

Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases

J Med Chem 2020 Oct 8;63(19):10773-10781.PMID:32667203DOI:10.1021/acs.jmedchem.0c00499.

Visceral leishmaniasis is responsible for up to 30,000 deaths every year. Current treatments have shortcomings that include toxicity and variable efficacy across endemic regions. Previously, we reported the discovery of GNF6702, a selective inhibitor of the kinetoplastid proteasome, which cleared parasites in murine models of leishmaniasis, Chagas disease, and human African trypanosomiasis. Here, we describe the discovery and characterization of LXE408, a structurally related kinetoplastid-selective proteasome inhibitor currently in Phase 1 human clinical trials. Furthermore, we present high-resolution cryo-EM structures of the Leishmania tarentolae proteasome in complex with LXE408, which provides a compelling explanation for the noncompetitive mode of binding of this novel class of inhibitors of the kinetoplastid proteasome.

Small molecules as kinetoplastid specific proteasome inhibitors for leishmaniasis: a patent review from 1998 to 2021

Expert Opin Ther Pat 2022 May;32(5):591-604.PMID:35220857DOI:10.1080/13543776.2022.2045948.

Introduction: Leishmaniasis is a neglected tropical infectious disease. The available limited therapeutic options for leishmaniasis are inadequate due to their poor pharmacokinetic profile, resistance, toxicity, high cost, and compliance problems. This warrants identification of new targets for the development of safer and effective anti-Leishmania therapy. The kinetoplastid specific proteasome (KSP) is a novel validated target to develop drugs against leishmaniasis. Area covered: This review focuses on all the published patent applications and granted patents related to the studied small molecules as KSP inhibitors (KSPIs) against Leishmania from 1998 to 31 December 2021. Expert opinion: A little amount of work has been done on KSPIs, but the study results are quite encouraging. LXE408 and GSK3494245 are two KSPIs in different phases of clinical trials. Some other small molecules have also shown KSP inhibitory potential, but they are not in clinical trials. The KSPIs are promising next-generation orally active patient compliant drugs against kinetoplastid diseases, including leishmaniasis. However, the main challenge to discover the KSPIs will be the resistance development and their selectivity against the proteasome of eukaryotic cells.