跳转至内容
Merck
CN
所有图片(2)

主要文件

查看所有文档

安全信息

914738

Sigma-Aldrich

KB02-SLF

≥95%

别名:

(R)-1-(3-(3-(2-(2-(2-((1-(2-Chloroacetyl)-1,2,3,4-tetrahydroquinolin-6-yl)oxy)acetamido)ethoxy)ethoxy)propanamido)phenyl)-3-(3,4-dimethoxyphenyl)propyl (S)-1-(3,3-dimethyl-2-oxopentanoyl)piperidine-2-carboxylate, Electrophilic PROTAC®, Heterobifunctional conjugate for E3 ubiquitin ligase discovery

登录查看公司和协议定价
所有图片(2)

About This Item

经验公式（希尔记法）:
C50H65ClN4O12
CAS号:
2384184-40-9
分子量:
949.52
MDL编号:
MFCD32263417
NACRES:
NA.22

ligand

electrophilic fragment

质量水平

100

方案

≥95%

表单

powder

储存温度

−20°C

SMILES字符串

O=C(CCl)N1CCCC2=CC(OCC(NCCOCCOCCC(NC3=CC=CC([C@H](OC([C@@H]4CCCCN4C(C(C(C)(C)CC)=O)=O)=O)CCC5=CC(OC)=C(OC)C=C5)=C3)=O)=O)=CC=C21

InChI

1S/C50H65ClN4O12/c1-6-50(2,3)47(59)48(60)55-23-8-7-14-40(55)49(61)67-41(19-15-34-16-20-42(62-4)43(29-34)63-5)36-11-9-13-37(30-36)53-44(56)21-25-64-27-28-65-26-22-52-45(57)33-66-38-17-18-39-35(31-38)12-10-24-54(39)46(58)32-51/h9,11,13,16-18,20,29-31,40-41H

InChI key

OKJBKEQXKMMRPL-WVILEFPPSA-N

相关类别

应用

KB02-SLF is an electrophilic PROTAC developed in the Cravatt lab and is useful for the discovery of ligandable E3 ligases, an area of interest for the targeted protein degradation (TPD) field seeking to map out and utilize a larger repertoire of the available human E3 ligases. This bifunctional tool compound comprises a synthetic ligand for FKBP12 (SLF) on one end and scout fragment 912131 on the other end. Scout fragments are electrophiles that covalently modify targetable cysteine residues on proteins, an approach that has been scaled to globally quantitate Cys reactivity across human proteomes and cells. When SLF and the electrophilic fragment are fused together, monitoring the levels of FKBP12 in cells may indicate scout-mediated FKBP12 degradation, for which follow-up studies would validate the mechanism of FKPB12 depletion and any targets to which the scout fragment is covalently bound. Scout-bound proteins leading to FKBP12 (or other targets) depletion discovered by this strategy will further expand the communal TPD toolbox. Due to the reactive nature of the scout fragment, other proteins will also be modified, so careful controls and validation should be considered.

This proteomic approach to E3 discovery was demonstrated by Zhang et al in the discovery that DCAF16 mediated nuclear FKBP12 degradation via KB02-SLF.

Additional electrophilic PROTACs were developed incorporating scout fragments with broad cysteine reactivity:
  • KB03-SLF (914975) containing chloroacetamide scout fragment 912654
  • KB05-SLF (913715) containing acrylamide scout fragment 911798


Related tools:
  • Additional bifunctional tools for FKPB12 variants: dTAG-13 (SML2601 for FKBP12F36V) and Biotin-SLF (914223 for FKBP12)
  • Inhibitors useful in validation of proteasomal-mediated degradation: MG123 (SML1135) and MLN4924 (5.05477for Cullin-RING ubiquitin ligases that regulate neddylation of Cullin proteins)
  • Cereblon (CRBN) affinity probe: Biotin-Thalidomide (913979)

其他说明

Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16

Technology Spotlight: Proteomic Ligandability Assessment

Technology Spotlight: Building PROTAC® Degraders for Targeted Protein Degradation

法律信息

PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license

储存分类代码

11 - Combustible Solids

WGK

WGK 3

闪点(°F)

Not applicable

闪点(°C)

Not applicable

法规信息

新产品

从最新的版本中选择一种：

分析证书(COA)

Lot/Batch Number

抱歉，我们目前尚未线上提供该产品的COA。

如需帮助，请联系 客户支持

已有该产品？

在文件库中查找您最近购买产品的文档。

访问文档库

Xiaoyu Zhang et al.
Nature chemical biology, 15(7), 737-746 (2019-06-19)
Ligand-dependent protein degradation has emerged as a compelling strategy to pharmacologically control the protein content of cells. So far, however, only a limited number of E3 ligases have been found to support this process. Here, we use a chemical proteomic

我们的科学家团队拥有各种研究领域经验，包括生命科学、材料科学、化学合成、色谱、分析及许多其他领域.

联系技术服务部门