Thalidomide-O-amido-C6-NH2 (TFA)

 CAS No.: 1950635-14-9  Cat No.: BP-100001  HNMR  HPLC  MS 4.5  

Thalidomide-O-amido-C6-NH2 (TFA) is a specialized E3 Ligase Ligand-Linker Conjugate designed for use in PROTAC (Proteolysis Targeting Chimera) drug development. This compound links a thalidomide-based E3 ligase ligand to a six-carbon amide linker terminating in a primary amine, offering versatile conjugation capabilities for the assembly of custom PROTAC molecules. Thalidomide derivatives are known to recruit the CRBN (Cereblon) E3 ubiquitin ligase, a popular target in targeted protein degradation research. Thalidomide-O-amido-C6-NH2 is ideal for medicinal chemistry applications requiring high purity E3 ligase recruiting elements equipped with functional linkers, supporting the generation of bifunctional molecules that promote target protein ubiquitination and subsequent proteasomal degradation. Perfect for emerging therapeutic strategies and proof-of-concept studies, this conjugate supports a variety of applications in chemical biology and drug discovery focused on harnessing the power of targeted protein degradation.

Thalidomide-O-amido-C6-NH2 (TFA)

Structure of 1950635-14-9

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Category
E3 Ligase Ligand-Linker Conjugate
Molecular Formula
C23H27F3N4O8
Molecular Weight
544.48

* For research and manufacturing use only. Not for human or clinical use.

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100 mg $439 In stock

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Popular Publications Citing BOC Sciences Products
Solubility
DMSO : ≥ 105.5 mg/mL
Storage
4°C, stored under nitrogen<br/>*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Shipping
Room temperature in continental US; may vary elsewhere
Synonyms
Thalidomide-O-amido-C6-NH2 (TFA); Cereblon Ligand-Linker Conjugates 11 (TFA); E3 Ligase Ligand-Linker Conjugates 25 (TFA); Thalidomide-O-amido-C6-Amine Trifluoroacetate; N-(6-aminohexyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetamide;2,2,2-trifluoroacetic acid
InChI Key
KNNGJZWEJKPKSW-UHFFFAOYSA-N
InChI
InChI=1S/C21H26N4O6.C2HF3O2/c22-10-3-1-2-4-11-23-17(27)12-31-15-7-5-6-13-18(15)21(30)25(20(13)29)14-8-9-16(26)24-19(14)28;3-2(4,5)1(6)7/h5-7,14H,1-4,8-12,22H2,(H,23,27)(H,24,26,28);(H,6,7)
Canonical SMILES
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)OCC(=O)NCCCCCCN.C(=O)(C(F)(F)F)O

Background Introduction

Thalidomide-O-amido-C6-NH2 (TFA) is a specialized E3 ligase ligand-linker conjugate widely utilized in the development of PROTACs (Proteolysis Targeting Chimeras) for targeted protein degradation. This compound incorporates thalidomide, which serves as a cereblon (CRBN) E3 ubiquitin ligase recruiter, and features a C6 amide linker terminating in a primary amine functional group (NH2), making it ideal for downstream conjugation.

Mechanism

Thalidomide-O-amido-C6-NH2 (TFA) functions as a modular building block in PROTAC synthesis. The thalidomide moiety binds specifically to the CRBN E3 ligase, recruiting the ubiquitination complex to the target protein. The C6 linker provides optimal spatial separation while the terminal amine enables convenient coupling with diverse warheads through standard amide bond formation or other chemical linkages. By bridging an E3 ligase and a protein-targeting warhead, the resulting PROTAC mediates ubiquitination and subsequent degradation of the target protein via the proteasome pathway.

Applications

Thalidomide-O-amido-C6-NH2 (TFA) is extensively used in chemical biology, drug discovery, and targeted protein degradation research. Its primary application is in constructing CRBN-based PROTACs for the study and selective elimination of disease-relevant proteins, such as kinases, transcription factors, and epigenetic regulators. The terminal NH2 functionality allows flexible conjugation to a wide range of ligands, enabling the rapid design and optimization of novel PROTAC molecules. Additionally, this conjugate can be leveraged in the development of molecular glues and other heterobifunctional therapeutics for oncology, neurodegenerative disorders, and immunology.

• Amine-functionalized linker enables easy and efficient conjugation to target ligands or payloads, streamlining PROTAC development.
• High affinity for the cereblon (CRBN) E4 ligase ensures reliable and robust degradation activity in PROTAC applications.
1. Global Surveillance of trans-Fatty Acids
Hubert W Vesper, Chaoyang Li, Samira Asma, Laura K Cobb Prev Chronic Dis . 2019 Oct 31;16:E147. doi: 10.5888/pcd16.190121.
Trans-fatty acid (TFA) intake can increase the risk of coronary heart disease (CHD) morbidity and mortality and all-cause mortality. Industrially produced TFAs and ruminant TFAs are the major sources in foods. TFA intake and TFA-attributed CHD mortality vary widely worldwide. Excessive TFA intake is a health threat in high-income countries; however, it is also a threat in low- and middle-income countries (LMICs). Data on TFA intake are scarce in many LMICs and an urgent need exists to monitor TFAs globally. We reviewed global TFA intake and TFA-attributed CHD mortality and current progress toward policy or regulation on elimination of industrially produced TFAs in foods worldwide. Human biological tissues can be used as biomarkers of TFAs because they reflect actual intake from various foods. Measuring blood TFA levels is a direct and reliable method to quantify TFA intake.
2. Trans-Fatty Acids and Cardiovascular Disease: Urgent Need for Legislation
Mateusz M Wilczek, Robert Olszewski, Andrzej Krupienicz Cardiology . 2017;138(4):254-258. doi: 10.1159/000479956.
Hydrogenated oils containing trans-fatty acids (TFA) are used to produce margarine and various processed foods. TFA affect serum lipid levels, fatty acid metabolism, and endothelial function. High TFA intake is linked to increased all-cause mortality, coronary heart disease mortality, and cardiovascular disease (CVD) incidence. Denmark was the first country to introduce a law that limited TFA content in food; this action led to lower CVD mortality. So far 7 European countries have followed this practice, in a few others the food industry voluntarily reduced TFA use. The issue remains mostly unaddressed in the rest of the world. Legal TFA limits should be commonly established as they are the optimal solution considering both CVD prevention and the associated cost savings in public healthcare.
3. The evidence of politics in trans-fatty acid regulation in Mexico
Ekow Adom Mensah, Nataliia Gavkalova, Israel Oluwaseyidayo Idris Salud Publica Mex . 2021 Feb 26;63(2, Mar-Abr):268-273. doi: 10.21149/11186.
According to the World Health Organization, coronary heart disease (CHD)-caused deaths accounted for one-fifth of the total deaths in Mexico in 2017. Researches done in the past have confirmed the association between dietary trans-fatty acids (TFA) and CHD. Dietary TFA are mostly derived from industrial-hydrogenated oils, milk products, and meat fats. This paper is a build on of a policy paper done on international policies for TFA in low-to-middle income countries, using Mexico as the case study. This write up, however, aims to critically analyse the TFA regulation policy process in Mexico, evaluating the strength of evidence proposed and identifying the barriers preventing the usage of the evidence for a TFA regulation policy implementation. Although evidence abounds for TFA regulation policy, lack of effective collaboration and communication among the major actors (researchers, policy-makers, and consumers) in Mexico remains a major setback in its implementation.

Hello, can Thalidomide-O-amido-C6-NH2 (TFA) be used for synthesizing PROTAC molecule?

Yes! Thalidomide-O-amido-C6-NH2 (TFA) can be used to synthesize PROTAC molecule.

4/1/2020

Could you describe Thalidomide-O-amido-C6-NH2 (TFA) in detail?

Of course I could. Thalidomide-O-amido-C6-NH2 TFA (Cereblon Ligand-Linker Conjugates 11 TFA) is a synthetic E3 ligand-Linker conjugates, Contains Thalidomide based cereblon ligand and 1 linker.

20/9/2021

synthesize PROTAC molecule

It was used to synthesize PROTAC molecule with a good yield in my experiment, would recommend.

13/1/2017

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2

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Tip: Chemical formula is case sensitive. C22H30N4O c22h30n40
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