Digital resources - Ha Noi university of science and technology

Browsing by Subject chất ức chế

Jump to: 0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
or enter first few letters:

Showing results 1 to 18 of 18

Journal article

A Recombinant Approach For Stapled Peptide Discovery Yields Inhibitors of the RAD51 Recombinase

Authors : Pantelejevs, Teodors (2023)

Stapling is a macrocyclisation method that connects amino acid side chains of a peptide to improve its pharmacological properties. We describe an approach for stapled peptide preparation and biochemical evaluation that combines recombinant expression of fusion constructs of target peptides and cysteine-reactive divinylheteroaryl chemistry, as an alternative to solid-phase synthesis. We then employ this workflow to prepare and evaluate BRC-repeatderived ...

Journal article

Analysis of single cells treated with the KRASG12D inhibitor MRTX 1133 reveals new challenges for the emerging field of single cell proteomics

Authors : Orsburn, Benjamin C. (2023)

Mutations in KRAS are common drivers of human cancers and are often those with the poorest overall prognosis for patients. A recently developed compound, MRTX1133 has shown promise in inhibiting the KRASG12D mutant protein, which is a primary driver mutation in pancreatic cancer cases worldwide. In this study, I performed a multi-omic analysis of four cancer cell lines following acute treatment with this compound. To obtain increased&#...

Journal article

Bioluminescence-based reporters for characterizing inhibitors and activators of human Sonic Hedgehog protein autoprocessing in live cells at high throughput

Authors : Ciulla, Daniel A (2023)

The Sonic hedgehog (SHh) precursor protein undergoes biosynthetic autoprocessing to cleave off and cholesterylate the SHh signaling ligand, a vital morphogen and oncogenic effector protein. Autoprocessing is self-catalyzed by SHhC, the SHh precursor’s enzymatic domain. Here we describe the development and validation of the first cellular reporter to monitor human SHhC autoprocessing non-invasively in high-throughput compatible plates. The assay couples intracellular SHhC autopro...

Journal article

Bisphenol A derivatives act as novel coactivator binding inhibitors for estrogen receptor β

Authors : Iwamoto, Masaki (2021)

Bisphenol A and its derivatives are recognized endocrine disruptors based on their complex effects on estrogen receptor (ER) signaling. While the effects of bisphenol derivatives on ERa have been thoroughly evaluated, how these chemicals affect ERb signaling is not well understood. Herein, we identified novel ERb ligands by screening a chemical library of bisphenol derivatives. Many of the compounds identified showed intriguing dual activities as ERa agonists...

Journal article

Combining cancer chemotherapeutics with bacterial DNA repair inhibitors to develop novel antimicrobials

Authors : Bernacchia, Lorenzo (2023)

Cancer chemotherapeutics kill rapidly dividing cells, which includes cells of the immune system. The 12 resulting neutropenia predisposes patients to infection, which delays treatment and is a major cause 13 of morbidity and mortality. Here we have exploited the cytotoxicity of the anti-cancer compound 14 cisplatin to screen for FDA-approved drugs that impair bacterial nucleotide excision DNA repair (NER), 15 the primary mechanism bacteria use to repair ...

Journal article

Computationally Guided Design of Novel Angiotensin Converting Enzyme Inhibitors

Authors : Lam, Jennifer D. (2023)

Angiotensin-converting enzyme inhibitors (ACEI) such as Moexipril, Trandolapril, Ramipril, and Perindopril are used to treat hypertension. However, these drugs have undesired side effects. Using computational studies, two new novel drug candidates were designed with improved molecular interactions, ADMET properties, and docking scores compared to Moexipril. Homology analysis was done to determine the best animal model for preclinical studies, and it revealed that Pan troglo...

Journal article

Discovery of Chlorofluoroacetamide-Based Covalent Inhibitors for SARS-CoV-2 3CL Protease

Authors : Hirose, Yuya (2023)

The pandemic of coronavirus disease 2019 (COVID-19) has urgently necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2). The 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report the new class of covalent inhibitors for 3CLpro possessing chlorofluoroacetamide (CFA) as a cysteine reactive warhead. Based on the aza-peptide scaffold, we synthesized the series...

Journal article

Discovery of diverse human BH3-only and non-native peptide binders of pro-apoptotic BAK indicate that activators and inhibitors use a similar binding mode and are not distinguished by binding affinity or kinetics

Authors : Aguilar, Fiona (2023)

Apoptosis is a programmed form of cell death important for the development and maintenance of tissue homeostasis. The BCL-2 protein family controls key steps in apoptosis, dysregulation of which can lead to a wide range of human diseases. BCL-2 proteins comprise three groups: anti-apoptotic proteins, proapoptotic proteins, and BH3-only proteins. BAK is one of two pro-apoptotic proteins, and previous work has shown that binding of certain&#x...

Journal article

Discovery of DTX3L inhibitors through a homogeneous FRET-based assay that monitors formation and removal of poly-ubiquitin chains

Authors : Rodríguez, Carlos Vela- (2023)

Ubiquitination is a complex and reversible protein post-translational modification in which the subsequent action of enzymes belonging to three different families, broadly referred to as E1, E2 and E3, results in the covalent linking of ubiquitin to a target protein. While this linkage is canonically an isopeptide bond between the C-terminus of ubiquitin and the lysine residue of the target protein, Ser, Thr, and Tyr can also be susceptible to&...

Journal Article

Drug repurposing approach for potential Pfmrk inhibitors as antimalarial agents: an In-silico analysis

Authors : Sahu, Abhishek (2023)

Malaria is a major global health issue due to the emergence of resistance to most of the available antimalarial drugs. There is an urgent need to discover new antimalarials to tackle the resistance issue. A CDK- like protein, Pfmrk from Plasmodium falciparum, plays a crucial role in regulating cell proliferation and shares 36.28% homology with humans CDK (hCDK7). Pfmrk complex with Pfcyc-1 and stimulates kinase activity. Also, Pfcyc-1 from P.&#...

Journal Article

Drug repurposing approach for potential Pfmrk inhibitors as antimalarial agents: an In-silico analysis

Authors : McBride, John M. (2023)

Alteration of one or few amino acid residues can affect structure [1–3] and function [4] of a protein and, in extreme cases, be the difference between health and disease [5, 6]. Understanding structural consequences of point mutations is important for drug design [7, 8] and could also accelerate optimization of enzymatic function via directed evolution [9, 10]. In these and other applications, theoretical models [11] could...

Journal Article

Fluorogenic Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide Activated SIRT7

Authors : Bolding, Julie E. (2023)

The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1–7) in humans, which are involved in the regulation of a plethora of biology, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ε-N-acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms; in part, because of a...

Journal article

Molecular determinants of TRAF6 binding specificity suggest that native interaction partners are not optimized for affinity

Authors : Halpin, Jackson C. (2023)

TRAF6 is an adapter protein and E3 ubiquitin ligase involved in signaling downstream of cell receptors essential for development and the immune system. TRAF6 participates in many protein-protein interactions, some of which are mediated by a C-terminal MATH domain that recruits TRAF6 to cell-surface receptors and associated proteins. The TRAF6 MATH domain binds to short peptide segments containing the motif PxExx[FYWHDE], where x is any amino acid. Blocki...

Industry article

Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily

Authors : Rak, Marcel (2023)

Salt-inducible kinases 1-3 (SIK1-3) are key regulators of the LKB1-AMPK pathway and play an important role in cellular homeostasis. Dysregulation of any of the three isoforms has been associated with tumorigenesis in liver, breast, and ovarian cancers. We have recently developed the dual pan-SIK/group I p21-activated kinase (PAK) chemical probe MRIA9. However, inhibition of p21-activated kinases has been associated with cardiotoxicity in vivo, w...

Journal article

Structure Activity Relationship of USP5 Allosteric Inhibitors

Authors : Mann, Mandeep K (2021)

USP5 is a deubiquitinase that has been implicated in a range of diseases, including cancer, but no USP5- targeting chemical probe has been reported to date. Here, we present the progression of a chemical series that occupies the C-terminal ubiquitin-binding site of a poorly characterized zinc-finger ubiquitin binding domain (ZnF-UBD) of USP5 and allosterically inhibits the catalytic activity of the enzyme. Systematic exploration of&...

Journal article

Structure-based design of selective salt-inducible kinase (SIK) inhibitors

Authors : Tesch, Roberta (2021)

Salt-inducible kinases (SIKs) are key metabolic regulators. Imbalance of SIK function is associated with the development of diverse cancers, including breast, gastric and ovarian cancer. Chemical tools to clarify the roles of SIK in different diseases are, however, sparse and are generally characterized by poor kinome-wide selectivity. Here, we have adapted the pyrido[2,3-d]pyrimidin-7-one-based PAK inhibitor G-5555 for the targeting of SIK, by exploiting differences i...

Journal article

VHL ligand binding increases intracellular level of VHL

Authors : Frost, Julianty (2021)

The von–Hippel Lindau (VHL) protein is a tumour suppressor protein frequently mutated in the VHL disease, which functions as substrate recognition subunit of a Cul2 E3 ubiquitin ligase (CRL2VHL). CRL2VHL plays an important role in oxygen sensing, by binding and targeting Hypoxia Inducible Factor-alpha subunits (HIF-alpha) for ubiquitination and degradation. VHL is also commonly hijacked by heterobifunctional degrader molecules known as...

Journal article

Zur and Zinc Increase Expression of E. coli Ribosomal Protein L31 Through RNA-Mediated Repression of the Repressor L31p

Authors : Rasmussen, Rebecca A. (2023)

Bacteria can adapt in response to numerous stress conditions. One such stress condition is zinc depletion. The zinc-sensing transcription factor Zur regulates the way enteric bacteria respond to severe changes in zinc availability. Under zinc sufficient conditions, Zn-loaded Zur (Zn2-Zur) is well-known to repress transcription of genes encoding zinc uptake transporters and paralogues of a few ribosomal subunits. Here, we report the discovery and mechanistic basis&...