SH-42
目录号 : GC49333An inhibitor of DHCR24
Cas No.:2143952-36-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SH-42 is an inhibitor of ?24-dehydrocholesterol reductase (DHCR24; IC50 = 4.2 nM).1 It increases serum levels of desmosterol , the immediate precursor of cholesterol in the Bloch pathway, in mice when administered at a dose of 0.5 mg/animal per day. SH-42 increases levels of arachidonic acid and its metabolite prostaglandin E2 , as well as docosahexaenoic acid and its metabolites 19,20-EpDPA and 19,20-DiHDPA, in the peritoneal lavage fluid in a mouse model of peritonitis induced by zymosan A .2
1.MÜller, C., Hemmers, S., Bartl, N., et al.New chemotype of selective and potent inhibitors of human delta 24-dehydrocholesterol reductaseEur. J. Med. Chem.140305-320(2017) 2.KÖrner, A., Zhou, E., MÜller, C., et al.Inhibition of δ24-dehydrocholesterol reductase activates pro-resolving lipid mediator biosynthesis and inflammation resolutionProc. Natl. Acad. Sci. USA116(41)20623-20634(2019)
| Cas No. | 2143952-36-5 | SDF | |
| Canonical SMILES | C[C@@]12[C@]3([H])C([C@@]4([H])[C@](CC3)([C@]([C@@H](COC=O)C)([H])CC4)C)=CC[C@@]1([H])C[C@H](CC2)OC(C)=O | ||
| 分子式 | C25H38O4 | 分子量 | 402.6 |
| 溶解度 | Chloroform: 10 mg/ml | 储存条件 | -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。 |
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| 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4839 mL | 12.4193 mL | 24.8385 mL |
| 5 mM | 0.4968 mL | 2.4839 mL | 4.9677 mL |
| 10 mM | 0.2484 mL | 1.2419 mL | 2.4839 mL |
| 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 | 只 |
| 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 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
New chemotype of selective and potent inhibitors of human delta 24-dehydrocholesterol reductase
Eur J Med Chem 2017 Nov 10;140:305-320.PMID:28964935DOI:10.1016/j.ejmech.2017.08.011
The enzyme Δ24-dehydrocholesterol reductase (DHCR24) catalyzes the reduction of the Δ24-double bond in the side chain of cholesterol precursors. Recent biochemical investigations fuel the hope that inhibition of DHCR24, resulting in an accumulation of desmosterol, can open new therapeutic options for treating hepatitis C virus infections, certain forms of cancer and atherosclerosis. In turn, there is a high need for selective, potent and non-toxic inhibitors of DHCR24. Previous reports as well as our re-evaluation showed that established DHCR24 inhibitors are not suitable for this purpose. Based on the lathosterol-derived amide MGI-21 (IC50 823 nM for inhibition of overall cholesterol biosynthesis in HL-60 cells) we performed a systematic variation of the side chain functionality and identified the steroidal 3,22-diols 29 and 30, as well as several esters thereof, as extremely potent (IC50 < 5 nM), selective, and non-toxic DHCR24 inhibitors. In mice, diester 27 (SH-42) led to a significant increase in plasma desmosterol levels. The new inhibitors described here are valuable tools for investigating the therapeutic potential of DHCR24 inhibition.