Tag: 900-1000

On January 30, 2020, Raheja, Raj; Jackman, Robin M.; Kahana, Jason A. published a patent.Computed Properties of 1949837-12-0 The title of the patent was Nanoparticle compositions. And the patent contained the following:

Provided herein are nanoparticle compositions comprising a pharmaceutically acceptable carrier and a compound of Formula: A-L-B. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Computed Properties of 1949837-12-0

The Article related to nanoparticle lyophilized formulation, Pharmaceuticals: Formulation and Compounding and other aspects.Computed Properties of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On June 19, 2019, Jain, Neeraj; Hartert, Keenan; Tadros, Saber; Fiskus, Warren; Havranek, Ondrej; Ma, Man Chun John; Bouska, Alyssa; Heavican, Tayla; Kumar, Dhiraj; Deng, Qing; Moore, Dalia; Pak, Christine; Liu, Chih Long; Gentles, Andrew J.; Hartmann, Elena; Kridel, Robert; Smedby, Karin Ekstrom; Juliusson, Gunnar; Rosenquist, Richard; Gascoyne, Randy D.; Rosenwald, Andreas; Giancotti, Filippo; Neelapu, Sattva S.; Westin, Jason; Vose, Julie M.; Lunning, Matthew A.; Greiner, Timothy; Rodig, Scott; Iqbal, Javeed; Alizadeh, Ash A.; Davis, R. Eric; Bhalla, Kapil; Green, Michael R. published an article.Product Details of 1949837-12-0 The title of the article was Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma. And the article contained the following:

The activated B cell (ABC-like) subtype of diffuse large B cell lymphoma (DLBCL) is characterized by chronic activation of signaling initiated by Ig μ (IgM). By analyzing the DNA copy number profiles of 1000 DLBCL tumors, we identified gains of 18q21.2 as the most frequent genetic alteration in ABC-like DLBCL. Using integrative anal. of matched gene expression profiling data, we found that the TCF4 (E2-2) transcription factor gene was the target of these alterations. Overexpression of TCF4 in ABC-like DLBCL cell lines led to its occupancy on Ig (IGHM) and MYC gene enhancers and increased expression of these genes at the transcript and protein levels. Inhibition of TCF4 activity with dominant-neg. constructs was synthetically lethal to ABC-like DLBCL cell lines harboring TCF4 DNA copy gains, highlighting these gains as an attractive potential therapeutic target. Furthermore, the TCF4 gene was one of the top BRD4-regulated genes in DLBCL cell lines. BET proteolysis-targeting chimera (PROTAC) ARV771 extinguished TCF4, MYC, and IgM expression and killed ABC-like DLBCL cells in vitro. In DLBCL xenograft models, ARV771 treatment reduced tumor growth and prolonged survival. This work highlights a genetic mechanism for promoting Ig signaling in ABC-like DLBCL and provides a functional rationale for the use of BET inhibitors in this disease. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Product Details of 1949837-12-0

The Article related to tcf4 mutation diffuse large b cell lymphoma copy number, Mammalian Pathological Biochemistry: Oncology and other aspects.Product Details of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On December 15, 2020, Liu, Yanli; Guo, Bingqian; Aguilera-Jimenez, Estrella; Chu, Vivian S.; Zhou, Jin; Wu, Zhong; Francis, Joshua M.; Yang, Xiaojun; Choi, Peter S.; Bailey, Swneke D.; Zhang, Xiaoyang published an article.Quality Control of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide The title of the article was Chromatin looping shapes KLF5-dependent transcriptional programs in human epithelial cancers. And the article contained the following:

Activation of transcription factors is a key driver event in cancer. We and others have recently reported that the Kruppel-like transcription factor KLF5 is activated in multiple epithelial cancer types including squamous cancer and gastrointestinal adenocarcinoma, yet the functional consequences and the underlying mechanisms of this activation remain largely unknown. Here we demonstrate that activation of KLF5 results in strongly selective KLF5 dependency for these cancer types. KLF5 bound lineage-specific regulatory elements and activated gene expression programs essential to cancer cells. HiChIP anal. revealed that multiple distal KLF5 binding events cluster and synergize to activate individual target genes. Immunoprecipitation-mass spectrometry assays showed that KLF5 interacts with other transcription factors such as TP63 and YAP1, as well as the CBP/EP300 acetyltransferase complex. Furthermore, KLF5 guided the CBP/EP300 complex to increase acetylation of H3K27, which in turn enhanced recruitment of the bromodomain protein BRD4 to chromatin. The 3D chromatin architecture aggregated KLF5-dependent BRD4 binding to activate Polymerase II (POL2) elongation at KLF5-target genes, which conferred a transcriptional vulnerability to proteolysis-targeting chimera (PROTAC)-induced degradation of BRD4. Our study demonstrates that KLF5 plays an essential role in multiple epithelial cancers by activating cancer-related genes through 3D chromatin loops, providing an evidence-based rationale for targeting the KLF5 pathway. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Quality Control of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

The Article related to epithelial cancer chromatin looping shape klf5 transcription, Mammalian Pathological Biochemistry: Oncology and other aspects.Quality Control of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On December 18, 2018, Chung, Chan-I.; Zhang, Qiang; Shu, Xiaokun published an article.Recommanded Product: 1949837-12-0 The title of the article was Dynamic Imaging of Small Molecule Induced Protein-Protein Interactions in Living Cells with a Fluorophore Phase Transition Based Approach. And the article contained the following:

Protein-protein interactions (PPIs) mediate signal transduction in cells. Small mols. that regulate PPIs are important tools for biol. and biomedicine. Dynamic imaging of small mol. induced PPIs characterizes and verifies these mols. in living cells. It is thus important to develop cellular assays for dynamic visualization of small mol. induced protein-protein association and dissociation in living cells. Here we have applied a fluorophore phase transition based principle and designed a PPI assay named SPPIER (separation of phases-based protein interaction reporter). SPPIER utilizes the green fluorescent protein (GFP) and is thus genetically encoded. Upon small mol. induced PPI, SPPIER rapidly forms highly fluorescent GFP droplets in living cells. SPPIER detects immunomodulatory drug (IMiD) induced PPI between cereblon and the transcription factor Ikaros. It also detects IMiD analog (e.g., CC-885) induced PPI between cereblon and GSPT1. Furthermore, SPPIER can visualize bifunctional mols. (e.g. PROTAC)-induced PPI between an E3 ubiquitin ligase and a target protein. Lastly, SPPIER can be modified to image small mol. induced protein-protein dissociation, such as nutlin-induced dissociation between HDM2 and p53. The intense brightness and rapid kinetics of SPPIER enable robust and dynamic visualization of PPIs in living cells. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Recommanded Product: 1949837-12-0

The Article related to fluorescent imaging protein interaction small mol induced, Biochemical Methods: Spectral and Related Methods and other aspects.Recommanded Product: 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On March 18, 2021, Mitsiades, Constantine S.; Shirasaki, Ryosuke; Matthews, Geoffrey M.; Gandolfi, Sara; De Matos Simoes, Ricardo published a patent.Formula: C49H60ClN9O7S2 The title of the patent was Methods for treating cancer using serial administration of E3 ubiquitin ligase degraders. And the patent contained the following:

The present invention relates, in part, to methods for treating cancer using serial administration of E3 ubiquitin ligase degraders. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Formula: C49H60ClN9O7S2

The Article related to e3 ubiquitin ligase degrader cancer therapy, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Formula: C49H60ClN9O7S2

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On May 19, 2021, Liu, Jing; Chen, He; Liu, Yi; Shen, Yudao; Meng, Fanye; Kaniskan, H. Umit; Jin, Jian; Wei, Wenyi published an article.Synthetic Route of 1949837-12-0 The title of the article was Cancer Selective Target Degradation by Folate-Caged PROTACs. And the article contained the following:

PROTACs (proteolysis targeting chimeras) are an emerging class of promising therapeutic modalities that degrade intracellular protein targets by hijacking the cellular ubiquitin-proteasome system. However, potential toxicity of PROTACs in normal cells due to the off-tissue on-target degradation effect limits their clin. applications. Precise control of a PROTAC’s on-target degradation activity in a tissue-selective manner could minimize potential toxicity/side-effects. To this end, we developed a cancer cell selective delivery strategy for PROTACs by conjugating a folate group to a ligand of the VHL E3 ubiquitin ligase, to achieve targeted degradation of proteins of interest (POIs) in cancer cells vs. noncancerous normal cells. We show that our folate-PROTACs, including BRD PROTAC (folate-ARV-771), MEK PROTAC (folate-MS432), and ALK PROTAC (folate-MS99), are capable of degrading BRDs, MEKs, and ALK, resp., in a folate receptor-dependent manner in cancer cells. This design provides a generalizable platform for PROTACs to achieve selective degradation of POIs in cancer cells. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Synthetic Route of 1949837-12-0

The Article related to preparation folate caged protac cancer toxicity, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Synthetic Route of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On February 28, 2018, Sun, B.; Fiskus, W.; Qian, Y.; Rajapakshe, K.; Raina, K.; Coleman, K. G.; Crew, A. P.; Shen, A.; Saenz, D. T.; Mill, C. P.; Nowak, A. J.; Jain, N.; Zhang, L.; Wang, M.; Khoury, J. D.; Coarfa, C.; Crews, C. M.; Bhalla, K. N. published an article.Synthetic Route of 1949837-12-0 The title of the article was Bet protein proteolysis targeting chimera (protac) exerts potent lethal activity against mantle cell lymphoma cells. And the article contained the following:

Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and nuclear factor-κB (NF-κB) target genes that undermines the growth and survival of mantle cell lymphoma (MCL) cells. However, BET bromodomain inhibitor (BETi) treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4 that potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1 and the NF-κB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the levels of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacol. properties compared with ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Cotreatment of ARV-771 with ibrutinib or the BCL2 antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior preclin. activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or -resistant MCL. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Synthetic Route of 1949837-12-0

The Article related to mantle cell lymphoma antitumor bet protein proteolysis, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Synthetic Route of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On February 13, 2020, Bernstein, Bradley E.; Doench, John G.; Najm, Fadi J. published a patent.SDS of cas: 1949837-12-0 The title of the patent was Methods of combinatorial drug screening and use of therapeutic targets thereof in cancer treatment. And the patent contained the following:

CRISPR-Cas9 has enabled a new generation of screening strategies to interrogate gene function. However, redundant genes and the complexity of functional gene networks can confound single gene knockout approaches. Furthermore, simple addition of two or more sgRNAs has shown only modest targeting efficacy in screening approaches. The present invention relates to combined orthogonal CRISPR-derived components to maximize gene targeting activity with minimal cross-talk and interference. The present invention also relates to efficient S. aureus Cas9 sgRNA design rules, which were paired with S. pyogenes Cas9 sgRNA design rules to achieve dual target gene inactivation in a high fraction of cells. Applicants developed a lentiviral vector and cloning strategy to generate high complexity pooled dual-knockout libraries and show that screening these libraries can identify combinatorial phenotypes, including synthetic lethal gene pairs across multiple cell types. The gene pairs can be targeted therapeutically and applicants disclose therapeutically effective combination therapies using agents such as AZD5153, CPI-203, OTX015, JQ1. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).SDS of cas: 1949837-12-0

The Article related to antitumor screening therapeutic drug target cancer treatment, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.SDS of cas: 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On April 30, 2018, Wang, Shihui; Li, Haiyan; Wang, Yue; Gao, Yang; Yu, Shanshan; Zhao, Qianqian; Jin, Xiangqun; Lu, Haibin published an article.Recommanded Product: 1949837-12-0 The title of the article was Design and synthesis of proteolysis targeting chimeras for inducing brd4 protein degradation. And the article contained the following:

In this paper, we synthesized a series of proteolysis targeting chimeras(PROTACs) using VHL E3 ligase ligands for BRD4 protein degradation One of the most promising compound 19g exhibited robust potency of BRD4 inhibition with IC50 value of (18.6±1.3) nmol/L, resp. Furthermore, compound 19g potently inhibited cell proliferation in BRD4-sensitive cell lines RS4;11 with IC50 value of (34.2±4.3) nmol/L and capable of inducing de-gradation of BRD4 protein at 0.4-0.6μmol/L in the RS4;11 leukemia cells. These data show that compound 19g is a highly potent and efficacious BRD4 degrader. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Recommanded Product: 1949837-12-0

The Article related to leukemia cell brd4 protein degradation proteolysis targeting chimera, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Recommanded Product: 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

On June 28, 2016, Raina, Kanak; Lu, Jing; Qian, Yimin; Altieri, Martha; Gordon, Deborah; Rossi, Ann Marie K.; Wang, Jing; Chen, Xin; Dong, Hanqing; Siu, Kam; Winkler, James D.; Crew, Andrew P.; Crews, Craig M.; Coleman, Kevin G. published an article.Application of 1949837-12-0 The title of the article was PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. And the article contained the following:

Prostate cancer has the second highest incidence among cancers in men worldwide and is the second leading cause of cancer deaths of men in the United States. Although androgen deprivation can initially lead to remission, the disease often progresses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR) signaling and is associated with a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance invariably emerges, and new therapies are urgently needed. Recently, inhibitors of bromodomain and extra-terminal (BET) family proteins have shown growth-inhibitory activity in preclin. models of CRPC. Here, we demonstrate that ARV-771, a small-mol. pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technol., demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. Unlike BET inhibitors, ARV-771 results in suppression of both AR signaling and AR levels and leads to tumor regression in a CRPC mouse xenograft model. This study is, to our knowledge, the first to demonstrate efficacy with a small-mol. BET degrader in a solid-tumor malignancy and potentially represents an important therapeutic advance in the treatment of CRPC. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Application of 1949837-12-0

The Article related to bromodomain extra terminal protein, bet, brd4, protac, prostate, protein degradation, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Application of 1949837-12-0

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics