Tag: 300-400

On November 11, 2021, Bricelj, Alesa; Dora Ng, Yuen Lam; Ferber, Dominic; Kuchta, Robert; Muller, Sina; Monschke, Marius; Wagner, Karl G.; Kronke, Jan; Sosic, Izidor; Gutschow, Michael; Steinebach, Christian published an article.Category: piperidines The title of the article was Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands. And the article contained the following:

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Category: piperidines

The Article related to protac crbn stability neosubstrate cereblon linker degradation, Pharmacology: Structure-Activity and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On March 16, 2018, Ishoey, Mette; Chorn, Someth; Singh, Natesh; Jaeger, Martin G.; Brand, Matthias; Paulk, Joshiawa; Bauer, Sophie; Erb, Michael A.; Parapatics, Katja; Muller, Andre C.; Bennett, Keiryn L.; Ecker, Gerhard F.; Bradner, James E.; Winter, Georg E. published an article.COA of Formula: C14H10N2O6 The title of the article was Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders. And the article contained the following:

Protein degradation is an emerging therapeutic strategy with a unique mol. pharmacol. that enables the disruption of all functions associated with a target. This is particularly relevant for proteins depending on mol. scaffolding, such as transcription factors or receptor tyrosine kinases (RTKs). To address tractability of multiple RTKs for chem. degradation by the E3 ligase CUL4-RBX1-DDB1-CRBN (CRL4CRBN), we synthesized a series of phthalimide degraders based on the promiscuous kinase inhibitors sunitinib and PHA665752. While both series failed to induce degradation of their consensus targets, individual mols. displayed pronounced efficacy in leukemia cell lines. Orthogonal target identification supported by mol. docking led us to identify the translation termination factor G1 to S phase transition 1 (GSPT1) as a converging off-target, resulting from inadvertent E3 ligase modulation. This research highlights the importance of monitoring degradation events that are independent of the resp. targeting ligand as a unique feature of small-mol. degraders. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).COA of Formula: C14H10N2O6

The Article related to sunitinib pha665752 phthalimide synthesis antitumor translation termination factor gspt1, Pharmacology: Structure-Activity and other aspects.COA of Formula: C14H10N2O6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On September 21, 2018, Steinebach, Christian; Lindner, Stefanie; Udeshi, Namrata D.; Mani, Deepak C.; Kehm, Hannes; Koepff, Simon; Carr, Steven A.; Guetschow, Michael; Kroenke, Jan published an article.Computed Properties of 1216805-11-6 The title of the article was Homo-PROTACs for the Chemical Knockdown of Cereblon. And the article contained the following:

The immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide, all approved for the treatment of multiple myeloma, induce targeted ubiquitination and degradation of Ikaros (IKZF1) and Aiolos (IKZF3) via the cereblon (CRBN) E3 ubiquitin ligase. IMiD-based proteolysis-targeting chimeras (PROTACs) can efficiently recruit CRBN to a protein of interest, leading to its ubiquitination and proteasomal degradation By linking two pomalidomide mols., we designed homobifunctional, so-called homo-PROTACs and investigated their ability to induce self-directed ubiquitination and degradation The homodimerized compound I was characterized as a highly potent and efficient CRBN degrader with only minimal effects on IKZF1 and IKZF3. The cellular selectivity of I for CRBN degradation was confirmed at the proteome level by quant. mass spectrometry. Inactivation by compound I did not affect proliferation of different cell lines, prevented pomalidomide-induced degradation of IKZF1 and IKZF3, and antagonized the effects of pomalidomide on multiple myeloma cells. Homobifunctional CRBN degraders will be useful tools for future biomedical investigations of CRBN-related signaling and may help to further elucidate the mol. mechanism of thalidomide analogs. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Computed Properties of 1216805-11-6

The Article related to phthalimido glutarimide synthesis antitumor cereblon ikzf1 ikzf3 multiple myeloma, Pharmacology: Structure-Activity and other aspects.Computed Properties of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On January 15, 2010, Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. published an article.Electric Literature of 1216805-11-6 The title of the article was New thalidomide analogues derived through Sonogashira or Suzuki reactions and their TNF expression inhibition profiles. And the article contained the following:

A library of new thalidomide C4/5 analogs containing either a Ph or alkyne tether were synthesized using Sonogashira or Suzuki cross coupling reactions from their aryl halogenated precursors. All thalidomide analogs were tested for their ability to inhibit the expression of the proinflammatory cytokine Tumor Necrosis Factor (TNF). More explicitly the use of a novel reporter system utilizing the promoter region of the TNF gene in a human T-cell line provided a rapid and effective measure of NFκB transcriptional activity. Several compounds either containing either an aryl-iso-Bu or aryl-isopropoxy group were the most effective in inhibiting TNF expression, and were several times more active than thalidomide itself. Five of the more active derivatives indicated an apoptotic response while one of these compounds, containing an aldehyde tether, showed possible influence of cell cycling effects. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Electric Literature of 1216805-11-6

The Article related to structure thalidomide analog preparation tnf inhibition cancer, Pharmacology: Structure-Activity and other aspects.Electric Literature of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On November 11, 2021, Bricelj, Alesa; Dora Ng, Yuen Lam; Ferber, Dominic; Kuchta, Robert; Muller, Sina; Monschke, Marius; Wagner, Karl G.; Kronke, Jan; Sosic, Izidor; Gutschow, Michael; Steinebach, Christian published an article.Category: piperidines The title of the article was Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands. And the article contained the following:

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Category: piperidines

The Article related to protac crbn stability neosubstrate cereblon linker degradation, Pharmacology: Structure-Activity and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Burslem, George M.; Ottis, Philipp; Jaime-Figueroa, Saul; Morgan, Alicia; Cromm, Philipp M.; Toure, Momar; Crews, Craig M. published an article in 2018, the title of the article was Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure-Degradation Relationships.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid And the article contains the following content:

The immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small-mol.-induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one-pot synthesis without purification that provides rapid access to a multitude of IMiD analogs. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure-activity relationship with only a few compounds showing sub-micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti-proliferative activity as well as Aiolos degradation could be identified for two IMiD analogs. This study provides useful insight into the structure-degradation relationships for mols. of this type as well as a rapid and robust method for IMiD synthesis. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to immunomodulator analog preparation structure protein degradation, cereblon, condensation reactions, imides, immunomodulatory drugs, protein degradation, Pharmacology: Structure-Activity and other aspects.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Burslem, George M.; Ottis, Philipp; Jaime-Figueroa, Saul; Morgan, Alicia; Cromm, Philipp M.; Toure, Momar; Crews, Craig M. published an article in 2018, the title of the article was Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure-Degradation Relationships.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid And the article contains the following content:

The immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small-mol.-induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one-pot synthesis without purification that provides rapid access to a multitude of IMiD analogs. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure-activity relationship with only a few compounds showing sub-micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti-proliferative activity as well as Aiolos degradation could be identified for two IMiD analogs. This study provides useful insight into the structure-degradation relationships for mols. of this type as well as a rapid and robust method for IMiD synthesis. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to immunomodulator analog preparation structure protein degradation, cereblon, condensation reactions, imides, immunomodulatory drugs, protein degradation, Pharmacology: Structure-Activity and other aspects.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On January 6, 2022, Anderson, Kenneth C.; Hideshima, Teru; Dhe-Paganon, Sirano; Seo, Hyuk-Soo; Mizutani, Takashi; Zhang, Tinghu published a patent.Category: piperidines The title of the patent was PRPK inhibitors. And the patent contained the following:

This disclosure relates to compounds of formula (I) as defined in the Specification. This disclosure also relates to methods of synthesizing the compound of formula I and using the compounds of formula I for treating a disease (e.g., cancer). The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Category: piperidines

The Article related to prpk inhibitor cancer, Pharmaceuticals: Formulation and Compounding and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 28, 2022, Lier, Svenja; Sellmer, Andreas; Orben, Felix; Heinzlmeir, Stephanie; Krauss, Lukas; Schneeweis, Christian; Hassan, Zonera; Schneider, Carolin; Schaefer, Arlette; Pongratz, Herwig; Engleitner, Thomas; Oellinger, Rupert; Kuisl, Anna; Bassermann, Florian; Schlag, Christoph; Kong, Bo; Dove, Stefan; Kuster, Bernhard; Rad, Roland; Reichert, Maximilian; Wirth, Matthias; Saur, Dieter; Mahboobi, Siavosh; Schneider, Guenter published an article.SDS of cas: 1216805-11-6 The title of the article was A novel Cereblon E3 ligase modulator with antitumor activity in gastrointestinal cancer. And the article contained the following:

Targeted protein degradation offers new opportunities to inactivate cancer drivers and has successfully entered the clinic. Ways to induce selective protein degradation include proteolysis targeting chimera (PROTAC) technol. and immunomodulatory (IMiDs) / next-generation Cereblon (CRBN) E3 ligase modulating drugs (CELMoDs). Here, we aimed to develop a MYC PROTAC based on the MYC-MAX dimerization inhibitor 10058-F4 derivative 28RH and Thalidomide, called MDEG-541. We show that a subgroup of gastrointestinal cancer cell lines and primary patient-derived organoids are MDEG-541 sensitive. Although MYC expression was regulated in a CRBN-, proteasome- and ubiquitin-dependent manner, we provide evidence that MDEG-541 induced the degradation of CRBN neosubstrates, including G1 to S phase transition 1/2 (GSPT1/2) and the Polo-like kinase 1 (PLK1). In sum, we have established a CRBN-dependent degrader of relevant cancer targets with activity in gastrointestinal cancers. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).SDS of cas: 1216805-11-6

The Article related to gastrointestinal cancer plk1 cereblon e3 ligase modulator antitumor, cereblon, gspt1, gspt2, myc, plk1, Placeholder for records without volume info and other aspects.SDS of cas: 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 9, 2017, Buckley, Dennis; Winter, Georg; Phillips, Andrew J.; Heffernan, Timothy; Bradner, James; Roberts, Justin; Nabet, Behnam published a patent.COA of Formula: C14H10N2O6 The title of the patent was Regulation of protein levels using ligand-binding domains for chemical regulation of proteolytic degradation. And the patent contained the following:

A method of modulating protein levels in vivo in a manner that avoids problems associated with CRISPR/Cas gene editing by making the protein susceptible to chem.-induced protein degradation is described. A sequence encoding a protein domain binding a heterobifunctional compound is inserted into the gene of interest, leading to synthesis of the fusion protein. One functional domain of the heterobifunctional compound binds to the fusion protein, and the other binds to a protein that recruits an E3 ubiquitin ligase leading to ubiquitination and degradation The use of FK506-binding proteins as the ligand-binding domains with heterobifunctional FK506 derivatives as the regulating mol. is demonstrated. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).COA of Formula: C14H10N2O6

The Article related to proteolysis induction fusion protein heterobifunctional ligand ubiquitination, General Biochemistry: Subcellular Processes and other aspects.COA of Formula: C14H10N2O6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem