CWHM-1008
目录号 : GC65299
CWHM-1008 是一种有效、可口服的抗疟疾剂，对药物不耐受型 Plasmodium falciparum 3D7 和耐受型 Dd2 的 EC50值分别为 46 和 21 nM。
Cas No.:2362539-97-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CWHM-1008 is a potent and orally active antimalarial agent, with EC50 values of 46 and 21 nM against drug-sensitive Plasmodium falciparum 3D7 and drug-resistant Dd2 strains, respectively[1].
[1]. Meyers MJ, et al. 4-Aryl Pyrrolidines as a Novel Class of Orally Efficacious Antimalarial Agents. Part 1: Evaluation of 4-Aryl- N-benzylpyrrolidine-3-carboxamides. J Med Chem. 2019 Mar 22.
| Cas No. | 2362539-97-5 | SDF | Download SDF |
| 分子式 | C22H26F3N3O | 分子量 | 405.46 |
| 溶解度 | DMSO : 250 mg/mL (616.58 mM; Need ultrasonic) | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4663 mL | 12.3317 mL | 24.6633 mL |
| 5 mM | 0.4933 mL | 2.4663 mL | 4.9327 mL |
| 10 mM | 0.2466 mL | 1.2332 mL | 2.4663 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。
CWHM-1008 Induces Apoptosis and Protective Autophagy through the Akt/mTOR Axis in LUAD Cells
J Oncol 2021 Sep 11;2021:5548128.PMID:35096055DOI:10.1155/2021/5548128.
Recent studies have revealed that antiparasitic agents showed promising inhibitory effects on tumors, raising a possibility that repositioning this class of drugs may shed new light on clinical therapy against tumors. CWHM-1008 is a novel class of antimalarial drug; however, the inhibitory impact of CWHM-1008 on lung adenocarcinoma (LUAD) cells remains unclear. This study aimed to explore the anticancer effect and underlying mechanisms of CWHM-1008 on LUAD cells in vitro and in vivo. Human LUAD cells, H358 and A549, were treated with varying concentrations of CWHM-1008 at different lengths of time. Cell viability, colony formation, cell count, flow cytometry findings, microtubule-associated protein-1 light chain 3-green- (LC3-) GFP/RFP adenovirus infection status, and the expression of apoptosis and autophagy-related proteins were examined. Potential effects of an autophagy inhibitor (LY294002) and constitutively active Akt plasmid (CA-Akt) on CWHM-1008-induced apoptosis were also examined. Our results showed that CWHM-1008 significantly inhibited proliferation, induced apoptosis, and enhanced autophagy flux by blocking the RAC-alpha serine/threonine-protein kinase/the mammalian target of rapamycin (Akt/mTOR) axis in two LUAD cells. In addition, autophagy inhibited by LY294002 or CA-Akt transfection accelerated CWHM-1008-induced apoptosis in those LUAD cells. Moreover, CWHM-1008 significantly inhibited the growth and induced apoptosis of A549 cell in nude mice in vivo. The present findings provide new insights into anticancer properties of CWHM-1008, suggesting that it may be an adjuvant treatment for LUAD treatment, warranting further study.
4-Aryl Pyrrolidines as a Novel Class of Orally Efficacious Antimalarial Agents. Part 1: Evaluation of 4-Aryl- N-benzylpyrrolidine-3-carboxamides
J Med Chem 2019 Apr 11;62(7):3503-3512.PMID:30856324DOI:10.1021/acs.jmedchem.8b01972.
Identification of novel chemotypes with antimalarial efficacy is imperative to combat the rise of Plasmodium species resistant to current antimalarial drugs. We have used a hybrid target-phenotype approach to identify and evaluate novel chemotypes for malaria. In our search for drug-like aspartic protease inhibitors in publicly available phenotypic antimalarial databases, we identified GNF-Pf-4691, a 4-aryl- N-benzylpyrrolidine-3-carboxamide, as having a structure reminiscent of known inhibitors of aspartic proteases. Extensive profiling of the two terminal aryl rings revealed a structure-activity relationship in which relatively few substituents are tolerated at the benzylic position, but the 3-aryl position tolerates a range of hydrophobic groups and some heterocycles. Out of this effort, we identified (+)-54b (CWHM-1008) as a lead compound. 54b has EC50 values of 46 and 21 nM against drug-sensitive Plasmodium falciparum 3D7 and drug-resistant Dd2 strains, respectively. Furthermore, 54b has a long half-life in mice (4.4 h) and is orally efficacious in a mouse model of malaria (qd; ED99 ∼ 30 mg/kg/day). Thus, the 4-aryl- N-benzylpyrrolidine-3-carboxamide chemotype is a promising novel chemotype for malaria drug discovery.