149299-82-1

Usage

Uses

Used in Pharmaceutical Research:
Hydroxy-PEG2-CH2CO2t-Bu is used as a reagent for the preparation of potentiator-corrector agonists targeting the ΔF508-CFTR mutant protein associated with cystic fibrosis. Its unique structure and functional groups make it a valuable tool in the development of therapeutic agents for this genetic disorder.
Used in Drug Delivery Systems:
In the pharmaceutical industry, Hydroxy-PEG2-CH2CO2t-Bu can be utilized as a component in the design of drug delivery systems. Its hydrophilic nature and the ability to modify the hydroxyl and carboxyl groups make it suitable for creating targeted drug carriers or improving the solubility and bioavailability of certain drugs.
Used in Chemical Synthesis:
Hydroxy-PEG2-CH2CO2t-Bu can also be employed in chemical synthesis as a versatile building block. The t-butyl protected carboxyl group allows for selective deprotection, enabling the synthesis of a variety of PEGylated compounds with potential applications in various fields, including medicine, materials science, and biotechnology.

Upstream product

• 5292-43-3 bromoacetic acid tert-butyl ester 
• 10049-21-5 sodium dihydrogenphosphate 
• 111-46-6 diethylene glycol 

Downstream Products

• 882518-89-0 tert-butyl 2-[2-[2-(p-tolylsulfonyloxy)ethoxy]ethoxy]acetate 
• 251564-45-1 tert-butyl 2-(2-(2-azidoethoxy)ethoxy)acetate 
• 1144518-54-6 {2-[2-(4-chloro-2-nitrophenoxy)ethoxy]ethoxy}acetic acid tert-butyl ester 

Relevant academic research and scientific papers

Protein degradation through covalent inhibitor-based PROTACs

Tremendous advancements in proteolysis targeting chimera (PROTAC) technology have been made in recent years. However, whether a covalent inhibitor-based PROTAC can be developed remains controversial. Here, we successfully developed chimeric degraders based on covalent inhibitors to degrade BTK and BLK kinases, demonstrating that covalent inhibitor-based PROTACs are viable and useful tools.

TARGET PROTEIN EED DEGRADATION-INDUCING DEGRADUCER, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DISEASES RELATED TO EED, EZH2, OR PRC2, COMPRISING SAME AS ACTIVE INGREDIENT

The present invention relates to a target protein degradation-inducing Degraducer, a preparation method thereof, and a pharmaceutical composition for preventing or treating diseases related to EED, EZH2, or PRC2 comprising same as an active ingredient. A novel compound represented by formula 1, according to the present invention is a Degraducer compound that induces degradation of a target protein, i.e., embryonic ectoderm development (EED) or polycomb repressive complex 2 (PRC2), utilizing cereblon E3 ubiquitin ligase, von Hippel-Lindau tumor suppressor (VHL) E3 ubiquitin ligase, mouse double minute 2 homolog (MDM2) E3 ubiquitin ligase, and cellular inhibitor of apoptosis protein 1 (cIAP) E3 ubiquitin ligase, wherein the compound has an aspect of remarkably achieving target protein degradation-inducing activity through a ubiquitin proteasome system (UPS), and therefore there is a useful effect in that it is possible to provide a pharmaceutical composition for preventing or treating diseases or conditions related to a target protein, and a functional health food composition for preventing or improving same, comprising said compound as an active ingredient.

Compound targeting ubiquitination degradation tyrosinase as well as preparation method and application thereof

A Tyr inhibitor kojic acid is covalently bound to a pomalidomide or VHL enzyme targeting ligand through a linkage chain to obtain a specific structure, and the preparation method is simple to operate and mild in condition. The generation of melanin is inhibited, the anti-melanin tumor effect is remarkable, and the safety period of vegetables and fruits can be remarkably prolonged. The compound targeted ubiquitination degradation tyrosinase provided by the invention has wide application prospects in medicine, food and cosmetics.

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma

Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.

PROTEOLYSIS TARGETING CHIMERIC (PROTAC) COMPOUND WITH E3 UBIQUITIN LIGASE BINDING ACTIVITY AND TARGETING ALPHA-SYNUCLEIN PROTEIN FOR TREATING NEURODEGENERATIVE DISEASES

The present disclosure relates to bifunctional compounds, which find utility as modulators of alpha-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/ inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure. Such diseases or disorders are alpha-synucleinopathies or neurodegenerative diseases associated with alpha-synuclein accumulation and aggregation, such as e.g. Parkinson Disease, Alzheimer's Disease, dementia, dementia with Lewy bodies or multiple system atrophy, in particular Parkinson's Disease.

Phosphatase Binding Compounds and Methods of Using Same

The present invention provides bifunctional compounds that efficiently dephosphorylate certain phospho-activated target proteins. Such target proteins can be any protein involved in the pathway of a disease or disorder, such as but not limited to cancer, neurodegeneration, metabolic disease, diabetes, insulin resistance, and so forth.

Identification and Characterization of von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that recruit an E3 ligase to a target protein to facilitate ubiquitination and subsequent degradation of that protein. While the field of targeted degraders is still relatively young, the potential for this modality to become a differentiated and therapeutic reality is strong, such that both academic and pharmaceutical institutions are now entering this interesting area of research. In this article, we describe a broadly applicable process for identifying degrader hits based on the serine/threonine kinase TANK-binding kinase 1 (TBK1) and have generalized the key structural elements associated with degradation activities. Compound 3i is a potent hit (TBK1 DC50 = 12 nM, Dmax = 96%) with excellent selectivity against a related kinase IKK?, which was further used as a chemical tool to assess TBK1 as a target in mutant K-Ras cancer cells.

KINASE INHIBITORS

There are provided compounds of formula I, wherein T, A, Q, Z, G, R4, R5a, R5b and n have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members

BENZOTHIOPHENE DERIVATIVES AS ESTROGEN RECEPTOR INHIBITORS

A compound of formula (I), or a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.

Design and synthesis of a hybrid potentiator-corrector agonist of the cystic fibrosis mutant protein ΔF508-CFTR

A developing therapy of cystic fibrosis caused by the ΔF508 mutation in CFTR employs correction of defective CFTR chloride channel gating by a 'potentiator' and of defective CFTR protein folding by a 'corrector'. Based on SAR data for phenylglycine-type potentiators and bithiazole correctors, we designed a hybrid molecule incorporating an enzymatic hydrolysable linker to deliver the potentiator (PG01) fragment 2 and the corrector (Corr-4a) fragment 13. The hybrid molecule 14 contained PG01-OH and Corr-4a-linker-CO2H moieties, linked with an ethylene glycol spacer through an ester bond. The potentiator 2 and corrector 13 fragments (after cleavage) had low micromolar potency for restoration of ΔF508-CFTR channel gating and cellular processing, respectively. Cleavage of hybrid molecule 14 by intestinal enzymes under physiological conditions produced the active potentiator 2 and corrector fragments 13, providing proof-of-concept for small-molecule potentiator-corrector hybrids as a single drug therapy for CF caused by the ΔF508 mutation.