2139348-63-1

Usage

Uses

Used in Protein Degradation Applications:
1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-4-yl)amino)-3,6,9,12,15-pentaoxa-18-octadecanoic acid is used as a protein degrader building block for the synthesis of molecules designed for targeted protein degradation. It plays a crucial role in the development of PROTAC (proteolysis-targeting chimeras) technology, where it serves as a component of conjugates that recruit the Cereblon (CRBN) E3 ligase for effective protein degradation.
Used in Drug Discovery and Development:
In the pharmaceutical industry, 1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-4-yl)amino)-3,6,9,12,15-pentaoxa-18-octadecanoic acid is utilized for the synthesis of novel protein degrader molecules, which can potentially lead to the development of new therapeutic agents. The ability to fine-tune the structure of this molecule allows for the exploration of various analogs to optimize target degradation, enhancing the prospects of discovering effective drugs for various diseases.
Used in Chemical Synthesis and Research:
1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-4-yl)amino)-3,6,9,12,15-pentaoxa-18-octadecanoic acid is also used in chemical synthesis and research settings, where its unique structure and reactivity can be explored for the development of new chemical entities and the advancement of synthetic methodologies.
Used in Parallel Synthesis:
1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-4-yl)amino)-3,6,9,12,15-pentaoxa-18-octadecanoic acid is employed in parallel synthesis techniques to rapidly generate PROTAC libraries with variations in crosslinker length, composition, and E3 ligase ligand. This approach accelerates the discovery process and allows for the screening of multiple analogs to identify the most effective protein degraders for specific targets.

Upstream product

• 835616-60-9 2‐(2,6‐dioxopiperidin‐3‐yl)‐4‐fluoroisoindoline‐1,3‐dione 
• 1446282-18-3 tert-butyl 1-amino-3,6,9,12,15-pentaoxaoctadecan-18-oate 

Relevant academic research and scientific papers

Discovery of novel BCR-ABL PROTACs based on the cereblon E3 ligase design, synthesis, and biological evaluation

Protein degradation is a promising strategy for drug development. Proteolysis-targeting chimeras (PROTACs) hijacking the E3 ligase cereblon (CRBN) exhibit enormous potential and universal degradation performance due to the small molecular weight of CRBN ligands. In this study, the CRBN-recruiting PROTACs were explored on the degradation of oncogenic fusion protein BCR-ABL, which drives the pathogenesis of chronic myeloid leukemia (CML). A series of novel PROTACs were synthesized by conjugating BCR-ABL inhibitor dasatinib to the CRBN ligand including pomalidomide and lenalidomide, and the extensive structure-activity relationship (SAR) studies were performed focusing on optimization of linker parameters. Therein, we uncovered that pomalidomide-based degrader 17 (SIAIS056), possessing sulfur-substituted carbon chain linker, exhibits the most potent degradative activity in vitro and favorable pharmacokinetics in vivo. Besides, degrader 17 also degrades a variety of clinically relevant resistance-conferring mutations of BCR-ABL. Furthermore, degrader 17 induces significant tumor regression against K562 xenograft tumors. Our study indicates that 17 as an efficacious BCR-ABL degrader warrants intensive investigation for the future treatment of BCR-ABL+ leukemia.

BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY

The present invention relates to compounds of formula (I) useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

TROPOMYOSIN RECEPTOR KINASE (TRK) DEGRADATION COMPOUNDS AND METHODS OF USE

This disclosure relates to bivalent compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the bivalent compounds, and to methods of use the bivalent compounds for the treatment of certain disease in a subject in need thereof. The disclosure also relates to methods for identifying such bivalent compounds.

AMIDE-BASED PROTEOLYSIS MODULATORS OF B-RAPIDLY ACCELERATED FIBROSARCOMA (BRAF) AND ASSOCIATED USES

The present application relates to novel compounds of Formula (I) containing a E3 ubiquitin ligase binding moiety linked to a Raf protein kinase binding moiety. The present application also includes methods and uses of the compounds, for example, for inhi

COMPOUNDS AND METHODS OF TREATING CANCERS

This disclosure relates to heterobifunctional compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the heterobifunctional compounds, and to methods of use the heterobifunctional compounds for the treatment of ce

COMPOUNDS TARGETING AND DEGRADING BCR-ABL PROTEIN AND ITS ANTITUMOR APPLICATION

The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor.

TROPOMYOSIN RECEPTOR KINASE (TRK) DEGRADATION COMPOUNDS AND METHODS OF USE

Bivalent compounds, compositions comprising one or more of the bivalent compounds, and methods of use the bivalent compounds for the treatment of certain disease in a subject in need thereof are provided. Methods for identifying such bivalent compounds are provided, either.

CYCLIC-AMP RESPONSE ELEMENT BINDING PROTEIN (CBP) AND/OR ADENOVIRAL E1A BINDING PROTEIN OF 300 KDA (P300) DEGRADATION COMPOUNDS AND METHODS OF USE

Bivalent compounds composition comprises one or more of the bivalent compounds. The bivalent compound comprises a cyclic-AMP response element binding protein (CBP) and/or adenoviral E1A binding protein of 300kDa (P300) ligand (CBP/P300 ligand) conjugated

ALK (anaplastic lymphoma kinase) protein degradation agent and anti-tumor application thereof

The invention discloses a compound in a formula (I) and an anti-tumor application thereof. The compound in the formula (I) has degradation and inhabitation functions on ALK target protein and mainly comprises four parts, the first part ALK-TKIs is a compound with ALK tyrosine kinase inhabitation activity; the second part LIN is different linkers; the third part ULM (ubiquitin ligase binding moiety) of VHL, CRBN or other protease micromolecular ligand with a ubiquitination function; the fourth part group A is carboxyl or deficiency and covalently binds ALK-TKIs with LIN and covalently binds LINwith ULM. A series of designed and synthesized compounds have wide pharmacological activity, have functions of degrading ALK protein and inhibiting ALK activity and can be applied to related tumor therapy.

Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction

An organic base-promoted chemoselective alkylation of lenalidomide with different halides was developed, which offers a novel approach to a highly functionalized lenalidomide-based PROTAC library under mild reaction conditions. DIPEA was found to act as an efficient base to trigger facile generation of arylamine alkylation products compared with inorganic bases. This library was successfully applied to BET PROTAC, which not only degraded BET protein but also effectively inhibited cancer cell proliferation.