PROTAC(H-PGDS)-7
(Synonyms: Proteolysis-targeting Chimera (Prostaglandin D Synthase (hematopoietic-type))-7) 目录号 : GC49728
PROTAC(H-PGDS)-7 是一种造血前列腺素 D 合酶 (H-PGDS) PROTAC 降解剂，DC50 为 17.3 pM。
Cas No.:2761281-50-7
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
PROTAC(H-PGDS)-7 is a proteolysis-targeting chimera (PROTAC) comprised of the hematopoietic prostaglandin D synthase (H-PGDS) inhibitor TFC-007 and the cereblon inhibitor pomalidomide .1 It induces degradation of H-PGDS in KU812 cells with a 50% degradation concentration (DC50) value of 17.3 pM, as well as decreases the production of prostaglandin D2 (PGD2) in the same cells.
1.Yokoo, H., Shibata, N., Endo, A., et al.Discovery of a highly potent and selective degrader targeting hematopoietic prostaglandin D synthase via in silico designJ. Med. Chem.64(21)15868-15882(2021)
| Cas No. | 2761281-50-7 | SDF | Download SDF |
| 别名 | Proteolysis-targeting Chimera (Prostaglandin D Synthase (hematopoietic-type))-7 | ||
| Canonical SMILES | O=C(N1CCN(C2=C(C(N(C3C(NC(CC3)=O)=O)C4=O)=O)C4=CC=C2)CC1)C(CC5)CCN5C6=CC=C(NC(C7=CN=C(OC8=CC=CC=C8)N=C7)=O)C=C6 | ||
| 分子式 | C40H38N8O7 | 分子量 | 742.8 |
| 溶解度 | DMSO: 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 | 1.3463 mL | 6.7313 mL | 13.4626 mL |
| 5 mM | 0.2693 mL | 1.3463 mL | 2.6925 mL |
| 10 mM | 0.1346 mL | 0.6731 mL | 1.3463 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。
Structure-activity relationship study of PROTACs against hematopoietic prostaglandin D2 synthase
RSC Med Chem 2022 Sep 23;13(12):1495-1503.PMID:PMC9749925DOI:10.1039/d2md00284a.
Degradation of hematopoietic prostaglandin D2 synthase (H-PGDS) by proteolysis-targeting chimeras (PROTACs) is expected to be important in the treatment of allergic diseases and Duchenne's muscular dystrophy. We recently reported that PROTAC(H-PGDS)-7 (PROTAC1), which is composed of H-PGDS inhibitor (TFC-007) and cereblon (CRBN) E3 ligase ligand (pomalidomide), showed potent H-PGDS degradation activity. Here, we investigated the structure-activity relationships of PROTAC1, focusing on the C4- or C5-conjugation of pomalidomide, in addition, the H-PGDS ligand exchanging from TFC-007 with the biaryl ether to TAS-205 with the pyrrole. Three new PROTACs were evaluated for H-PGDS affinity, H-PGDS degrading activity, and inhibition of prostaglandin D2 production. All compounds showed high H-PGDS degrading activities, but PROTAC(H-PGDS)-4-TAS-205 (PROTAC3) was slightly less active than the other compounds. Molecular dynamics simulations suggested that the decrease in activity of PROTAC3 may be due to the lower stability of the CRBN-PROTAC-H-PGDS ternary complex.
Discovery of a Highly Potent and Selective Degrader Targeting Hematopoietic Prostaglandin D Synthase via In Silico Design
J Med Chem 2021 Nov 11;64(21):15868-15882.PMID:34652145DOI:10.1021/acs.jmedchem.1c01206.
Targeted protein degradation by proteolysis-targeting chimera (PROTAC) is one of the exciting modalities for drug discovery and biological discovery. It is important to select an appropriate linker, an E3 ligase ligand, and a target protein ligand in the development; however, it is necessary to synthesize a large number of PROTACs through trial and error. Herein, using a docking simulation of the ternary complex of a hematopoietic prostaglandin D synthase (H-PGDS) degrader, H-PGDS, and cereblon, we have succeeded in developing PROTAC(H-PGDS)-7 (6), which showed potent and selective degradation activity (DC50 = 17.3 pM) and potent suppression of prostaglandin D2 production in KU812 cells. Additionally, in a Duchenne muscular dystrophy model using mdx mice with cardiac hypertrophy, compound 6 showed better inhibition of inflammatory cytokines than a potent H-PGDS inhibitor TFC-007. Thus, our results demonstrated that in silico simulation would be useful for the rational development of PROTACs.