Category: 72835-26-8

Saha, M. N. published the artcileSmall molecule MIRA-1 induces in vitro and in vivo anti-myeloma activity and synergizes with current anti-myeloma agents, Quality Control of 72835-26-8, the main research area is small mol MIRA1 antimyeloma doxorubicin dexamethasone Velcade synergism; multiple myeloma.

Background: Small mol. MIRA-1 induced mutant p53-dependent apoptosis in several types of solid tumors. However, anti-tumor activity of MIRA-1 in haematol. malignancies including multiple myeloma (MM) is unknown. In this study, we evaluated the effect of MIRA-1 in MM. Methods: We examined the anti-tumor activity of MIRA-1 alone or in combination with current anti-myeloma agents in a panel of MM cell lines, primary MM samples, and in a mouse xenograft model of MM. Results: MIRA-1 treatment resulted in the inhibition of viability, colony formation, and migration and increase in apoptosis of MM cells irresp. of p53 status accompanied by upregulation of Puma and Bax and downregulation of Mcl-1 and c-Myc. Genetic knockdown of p53 did not abrogate apoptotic response of MIRA-1. MIRA-1 triggered activation of PERK and IRE-α leading to splicing of XBP1 indicating an association of endoplasmic reticulum stress response. Furthermore, combined treatment of MIRA-1 with dexamethasone, doxorubicin or velcade displayed synergistic response in MM cells. Importantly, MIRA-1 alone or in combination with dexamethasone retarded tumor growth and prolonged survival without showing any untoward toxicity in the mice bearing MM tumor. Conclusions: Our data provide the preclin. framework for clin. evaluation of MIRA-1 as a novel therapeutic agent to improve patient outcome in MM.

British Journal of Cancer published new progress about Apoptosis. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Quality Control of 72835-26-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Park, Min-Sun published the artcileEvaluating Docking Methods for Prediction of Binding Affinities of Small Molecules to the G Protein βγ Subunits, Synthetic Route of 72835-26-8, the main research area is docking mol G protein betagamma subunit.

Several studies have suggested that disrupting interactions of the G protein βγ subunits with downstream binding partners might be a valuable study for pharmaceutical development. Recently, small mols. have been found which bind to Gβγ with high apparent affinity in an ELISA, have demonstrated selective inhibition of interactions of Gβγ with downstream signaling partners, and have been shown to increase antinociceptive effects of morphine and inhibit inflammation in vivo. In this paper we examine several docking and scoring protocols for estimating binding affinities for a set of 830 ligands from the NCI diversity set to the Gβ1γ2 subunit and compared these with IC50s measured in a competition ELISA with a high-affinity peptidic ligand. The best-performing docking protocol used a consensus score and ensemble docking and resulted in a 6-fold enrichment of high-affinity compounds in the top-ranked 5% of the ligand data set.

Journal of Chemical Information and Modeling published new progress about Analgesics. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Synthetic Route of 72835-26-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Saha, M. N. published the artcileSmall molecule MIRA-1 induces in vitro and in vivo anti-myeloma activity and synergizes with current anti-myeloma agents, Quality Control of 72835-26-8, the main research area is small mol MIRA1 antimyeloma doxorubicin dexamethasone Velcade synergism; multiple myeloma.

Background: Small mol. MIRA-1 induced mutant p53-dependent apoptosis in several types of solid tumors. However, anti-tumor activity of MIRA-1 in haematol. malignancies including multiple myeloma (MM) is unknown. In this study, we evaluated the effect of MIRA-1 in MM. Methods: We examined the anti-tumor activity of MIRA-1 alone or in combination with current anti-myeloma agents in a panel of MM cell lines, primary MM samples, and in a mouse xenograft model of MM. Results: MIRA-1 treatment resulted in the inhibition of viability, colony formation, and migration and increase in apoptosis of MM cells irresp. of p53 status accompanied by upregulation of Puma and Bax and downregulation of Mcl-1 and c-Myc. Genetic knockdown of p53 did not abrogate apoptotic response of MIRA-1. MIRA-1 triggered activation of PERK and IRE-α leading to splicing of XBP1 indicating an association of endoplasmic reticulum stress response. Furthermore, combined treatment of MIRA-1 with dexamethasone, doxorubicin or velcade displayed synergistic response in MM cells. Importantly, MIRA-1 alone or in combination with dexamethasone retarded tumor growth and prolonged survival without showing any untoward toxicity in the mice bearing MM tumor. Conclusions: Our data provide the preclin. framework for clin. evaluation of MIRA-1 as a novel therapeutic agent to improve patient outcome in MM.

British Journal of Cancer published new progress about Apoptosis. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Quality Control of 72835-26-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Park, Min-Sun published the artcileEvaluating Docking Methods for Prediction of Binding Affinities of Small Molecules to the G Protein βγ Subunits, Synthetic Route of 72835-26-8, the main research area is docking mol G protein betagamma subunit.

Several studies have suggested that disrupting interactions of the G protein βγ subunits with downstream binding partners might be a valuable study for pharmaceutical development. Recently, small mols. have been found which bind to Gβγ with high apparent affinity in an ELISA, have demonstrated selective inhibition of interactions of Gβγ with downstream signaling partners, and have been shown to increase antinociceptive effects of morphine and inhibit inflammation in vivo. In this paper we examine several docking and scoring protocols for estimating binding affinities for a set of 830 ligands from the NCI diversity set to the Gβ1γ2 subunit and compared these with IC50s measured in a competition ELISA with a high-affinity peptidic ligand. The best-performing docking protocol used a consensus score and ensemble docking and resulted in a 6-fold enrichment of high-affinity compounds in the top-ranked 5% of the ligand data set.

Journal of Chemical Information and Modeling published new progress about Analgesics. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Synthetic Route of 72835-26-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Omar, Sara Ibrahim published the artcileRanking the Binding Energies of p53 Mutant Activators and Their ADMET Properties, Application In Synthesis of 72835-26-8, the main research area is p53 activator antitumor binding pharmacokinetics; ADMET properties; MD simulations; P53 activators; docking; p53-R273H.

The guardian of the genome, p53, is the most mutated protein found in all cancer cells. Restoration of wild-type activity to mutant p53 offers promise to eradicate cancer cells using novel pharmacol. agents. Several mols. have already been found to activate mutant p53. While the exact mechanism of action of these compounds has not been fully understood, a transiently open pocket has been identified in some mutants. In our study, we docked twelve known activators to p53 into the open pocket to further understand their mechanism of action and rank the best binders. In addition, we predicted the absorption, distribution, metabolism, excretion and toxicity properties of these compounds to assess their pharmaceutical usefulness. Our studies showed that alkylating ligands do not all bind at the same position, probably due to their varying sizes. In addition, we found that non-alkylating ligands are capable of binding at the same pocket and directly interacting with Cys124. The comparison of the different ligands demonstrates that stictic acid has a great potential as a p53 activator in terms of less adverse effects although it has poorer pharmacokinetic properties.

Chemical Biology & Drug Design published new progress about Antitumor agents. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Application In Synthesis of 72835-26-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Moles, R. published the artcileWRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells, Related Products of esters-buliding-blocks, the main research area is WRN NSC apoptosis HTLV Tcell leukemia cell; Adult T-cell leukemia/lymphoma (ATLL); Apoptosis; Cycle arrest; Human T-cell leukemia virus type 1 (HTLV-1); WRN helicase.

Background: Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATLL), a lymphoproliferative malignancy with a dismal prognosis and limited therapeutic options. Recent evidence shows that HTLV-1-transformed cells present defects in both DNA replication and DNA repair, suggesting that these cells might be particularly sensitive to treatment with a small helicase inhibitor. Because the “”Werner syndrome ATP-dependent helicase”” encoded by the WRN gene plays important roles in both cellular proliferation and DNA repair, we hypothesized that inhibition of WRN activity could be used as a new strategy to target ATLL cells. Methods: Our anal. demonstrates an apoptotic effect induced by the WRN helicase inhibitor in HTLV-1-transformed cells in vitro and ATL-derived cell lines. Inhibition of cellular proliferation and induction of apoptosis were demonstrated with cell cycle anal., XTT proliferation assay, clonogenic assay, annexin V staining, and measurement of mitochondrial transmembrane potential. Results: Targeted inhibition of the WRN helicase induced cell cycle arrest and apoptosis in HTLV-1-transformed leukemia cells. Treatment with NSC 19630 (WRN inhibitor) induces S-phase cell cycle arrest, disruption of the mitochondrial membrane potential, and decreased expression of anti-apoptotic factor Bcl-2. These events were associated with activation of caspase-3-dependent apoptosis in ATL cells. We identified some ATL cells, ATL-55T and LMY1, less sensitive to NSC 19630 but sensitive to another WRN inhibitor, NSC 617145. Conclusions: WRN is essential for survival of ATL cells. Our studies suggest that targeting the WRN helicase with small inhibitors is a novel promising strategy to target HTLV-1-transformed ATL cells.

Journal of Hematology & Oncology published new progress about Antitumor agents. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Related Products of esters-buliding-blocks.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Aggarwal, Monika published the artcileInhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress, Formula: C8H9NO4, the main research area is Werner syndrome helicase inhibitor NSC19630 topotecan synergism antitumor.

Modulation of DNA repair proteins by small mols. has attracted great interest. An in vitro helicase activity screen was used to identify mols. that modulate DNA unwinding by Werner syndrome helicase (WRN), mutated in the premature aging disorder Werner syndrome. A small mol. from the National Cancer Institute Diversity Set designated NSC 19630 [1-(propoxymethyl)-maleimide] was identified that inhibited WRN helicase activity but did not affect other DNA helicases [Bloom syndrome (BLM), Fanconi anemia group J (FANCJ), RECQ1, RecQ, UvrD, or DnaB]. Exposure of human cells to NSC 19630 dramatically impaired growth and proliferation, induced apoptosis in a WRN-dependent manner, and resulted in elevated γ-H2AX and proliferating cell nuclear antigen (PCNA) foci. NSC 19630 exposure led to delayed S-phase progression, consistent with the accumulation of stalled replication forks, and to DNA damage in a WRN-dependent manner. Exposure to NSC 19630 sensitized cancer cells to the G-quadruplex-binding compound telomestatin or a poly(ADP ribose) polymerase (PARP) inhibitor. Sublethal dosage of NSC 19630 and the chemotherapy drug topotecan acted synergistically to inhibit cell proliferation and induce DNA damage. The use of this WRN helicase inhibitor mol. may provide insight into the importance of WRN-mediated pathway(s) important for DNA repair and the replicational stress response.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Antitumor agents. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Formula: C8H9NO4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wu, Alexander T. H. published the artcileIdentification of a Novel Theranostic Signature of Metabolic and Immune-Inflammatory Dysregulation in Myocardial Infarction, and the Potential Therapeutic Properties of Ovatodiolide, a Diterpenoid Derivative, SDS of cas: 72835-26-8, the main research area is myocardial infarction gene regulatory network ovatodiolide therapeutic property; DEG; inflammatory and metabolic dysregulation; miRNA; myocardial infarction; ovatodiolide; theranostic.

Myocardial infarction (MI) is a multifactorial global disease, recognized as one of the leading causes of cardiovascular morbidity and mortality. Timely and correct diagnoses and effective treatments could significantly reduce incidence of complications and improve patient prognoses. In this study, seven unconventional differentially expressed genes (DEGs) (MAN2A2, TNFRSF12A, SPP1, CSNK1D, PLAUR, PFKFB3, and CXCL16, collectively termed the MTSCPPC signature) were identified through integrating DEGs from six MI microarray datasets. The pathol. and theranostic roles of the MTSCPPC signature in MI were subsequently analyzed. We evaluated interactions of the MTSCPPC signature with ovatodiolide, a bioactive compound isolated from Anisomeles indica (L.) Kuntze, using in silico mol. docking tools and compared it to specific inhibitors of the members of the MTSCPPC signature. Single-cell transcriptomic anal. of the public databases revealed high expression levels of the MTSCPPC signature in immune cells of adult human hearts during an MI event. The MTSCPPC signature was significantly associated with the cytokine-cytokine receptor interactions, chemokine signaling, immune and inflammatory responses, and metabolic dysregulation in MI. Anal. of a micro (mi)RNA regulatory network of the MTSCPPC signature suggested post-transcriptional activation and the roles of miRNAs in the pathol. of MI. Our mol. docking anal. suggested a higher potential for ovatodiolide to target MAN2A2, CSNK1D, and TNFRSF12A. Collectively, the results derived from the present study further advance our understanding of the complex regulatory mechanisms of MI and provide a potential MI theranostic signature with ovatodiolide as a therapeutic candidate.

International Journal of Molecular Sciences published new progress about Adult, mammalian. 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, SDS of cas: 72835-26-8.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Riesenberg, Stephan published the artcileTargeting repair pathways with small molecules increases precise genome editing in pluripotent stem cells, Formula: C8H9NO4, the main research area is genome editing targeted nucleotide substitution induced pluripotent stem cell.

A now frequently used method to edit mammalian genomes uses the nucleases CRISPR/Cas9 and CRISPR/Cpf1 or the nickase CRISPR/Cas9n to introduce double-strand breaks which are then repaired by homol.-directed repair using DNA donor mols. carrying desired mutations. Using a mixture of small mols., the “”CRISPY”” mix, we achieve a 2.8- to 7.2-fold increase in precise genome editing with Cas9n, resulting in the introduction of the intended nucleotide substitutions in almost 50% of chromosomes or of gene encoding a blue fluorescent protein in 27% of cells, to our knowledge the highest editing efficiency in human induced pluripotent stem cells described to date. Furthermore, the CRISPY mix improves precise genome editing with Cpf1 2.3- to 4.0-fold, allowing almost 20% of chromosomes to be edited. The components of the CRISPY mix do not always increase the editing efficiency in the immortalized or primary cell lines tested, suggesting that employed repair pathways are cell-type specific.

Nature Communications published new progress about CD34 antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Formula: C8H9NO4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wassman, Christopher D. published the artcileComputational identification of a transiently open L1/S3 pocket for reactivation of mutant p53, Product Details of C8H9NO4, the main research area is binding pocket loop1 sheet3 pocket reactivation protein p53; stictic acid reactivation p53 protein osteocarcinoma antitumor.

The tumor suppressor p53 is the most frequently mutated gene in human cancer. Reactivation of mutant p53 by small mols. is an exciting potential cancer therapy. Although several compounds restore wild-type function to mutant p53, their binding sites and mechanisms of action are elusive. Here computational methods identify a transiently open binding pocket between loop L1 and sheet S3 of the p53 core domain. Mutation of residue Cys124, located at the center of the pocket, abolishes p53 reactivation of mutant R175H by PRIMA-1, a known reactivation compound Ensemble-based virtual screening against this newly revealed pocket selects stictic acid as a potential p53 reactivation compound In human osteosarcoma cells, stictic acid exhibits dose-dependent reactivation of p21 expression for mutant R175H more strongly than does PRIMA-1. These results indicate the L1/S3 pocket as a target for pharmaceutical reactivation of p53 mutants.

Nature Communications published new progress about Animal gene, TP53 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 72835-26-8 belongs to class esters-buliding-blocks, name is (2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl propionate, and the molecular formula is C8H9NO4, Product Details of C8H9NO4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics