KDU731
目录号 : GC38033
KDU731，具有口服活性的 C. parvum PI4K 抑制剂，阻断体内外隐孢子虫感染，IC50 值为 25 nM。KDU731 是治疗隐孢子虫引起的腹泻的有望候选药物，具有广泛的安全性。
Cas No.:1610610-48-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
KDU731, an orally active C. parvum PI4K inhibitor with an IC50 value of 25 nM, blocks Cryptosporidium infection in vitro and in vivo[1][2]. KDU731 is a promising drug candidate for the treatment of diarrhea caused by Cryptosporidium and meets a broad range of safety[2].
KDU731 (orally administration; 7 or 10mg/kg; 16 days) has potent activity against Cryptosporidium in immunocompromised IFN-γ KO mice and dramatically reduces oocyst shedding[2].KDU731 (orally administration; 5 mg/kg; every 12 hours for 7 days) is tolerated in all calves, and treated calves shed significantly fewer oocysts than vehicle treated calves in their stool[2]. Animal Model: 6-8 week old C57BL/6 IFN-γ-knockout mice with 10,000 oocysts[1]
[1]. Ward HD, et al. New Tools for Cryptosporidium Lead to New Hope for Cryptosporidiosis. Trends Parasitol. 2017 Sep;33(9):662-664. [2]. Manjunatha UH, et al. A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis. Nature. 2017 Jun 15;546(7658):376-380.
| Cas No. | 1610610-48-4 | SDF | |
| Canonical SMILES | O=C(C1=CC2=C(C3=CC=C(C(N)=O)C=C3)C=NN2C=C1)N(C)C4=NC=C(C#N)C=C4 | ||
| 分子式 | C22H16N6O2 | 分子量 | 396.4 |
| 溶解度 | DMSO: 83.33 mg/mL (210.22 mM) | 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。 |
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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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.5227 mL | 12.6135 mL | 25.227 mL |
| 5 mM | 0.5045 mL | 2.5227 mL | 5.0454 mL |
| 10 mM | 0.2523 mL | 1.2614 mL | 2.5227 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。
Novel treatment strategies and drugs in development for cryptosporidiosis
Expert Rev Anti Infect Ther 2018 Aug;16(8):655-661.PMID:30003818DOI:10.1080/14787210.2018.1500457.
Cryptosporidium is a protozoan pathogen that can cause diarrheal disease in healthy and immunosuppressed individuals, worldwide. Recent studies have highlighted the impact of cryptosporidiosis on children in resource-limited countries. Nitazoxanide is the only Food and Drug Administration approved treatment, but it is not consistently effective therapy for cryptosporidiosis in the most vulnerable populations. Areas covered: This review focused on recent published studies evaluating novel drugs and new compounds for the treatment of cryptosporidiosis. Expert commentary: Combinations of approved drugs have demonstrated some activity. Broad screens have demonstrated activity against Cryptosporidium for a number of available drugs, including statins and clofazimine, and the latter has advanced into clinical trials. Cryptosporidium calcium-dependent protein kinase 1 (CDPK1) has been identified as an attractive target for treatment, and bumped kinase inhibitors have been developed which inhibit CDPK1 and are active against Cryptosporidium growth both in vitro and in vivo. Inhibition of Plasmodium lipid kinase PI(4)K8 of Cryptosporidium by KDU731 greatly reduced oocyst shedding and improved diarrhea in calves with limited effects on the human PI(4)K. Another novel potent inhibitor MMV665917 was efficacious in mouse models with cidal activity against Cryptosporidium. Additional compounds have proved active in vitro. So far, only clofazimine has entered human trials.
A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis
Nature 2017 Jun 15;546(7658):376-380.PMID:28562588DOI:10.1038/nature22337.
Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.
New Tools for Cryptosporidium Lead to New Hope for Cryptosporidiosis
Trends Parasitol 2017 Sep;33(9):662-664.PMID:28750950DOI:10.1016/j.pt.2017.07.004.
The pyrazolopyridine KDU731 is a promising drug candidate for treatment of diarrhea caused by Cryptosporidium in young children in the resource-limited world. KDU731, a PI (4) kinase inhibitor, blocks Cryptosporidium infection in vitro and in vivo in immunocompromised mice and dramatically reduces oocyst shedding, diarrhea, and dehydration in neonatal calves.