- |||||||||| Journal: Characterization of Ksg1 protein kinase-dependent phosphoproteome in the fission yeast S. pombe. (Pubmed Central) - Nov 13, 2024
Importantly, proteins with significantly down-regulated phosphorylation were specifically enriched for R-X-X-S and R-X-R-X-X-S motifs, which are typical consensus substrate sequences for phosphorylation by the AGC family of kinases. The results of this study provide a basis for further analysis of the role of the Ksg1 kinase and its targets in S. pombe and may also be useful for studying Ksg1 orthologs in other organisms.
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
An Orally Active Pan-BCR::ABL1 Degrader Tgrx-3247 Potently Targets a Wide Spectrum of Orthosteric, Allosteric and Compound Mutations Resistant to TKI Therapies (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5251;
With such potent and continuous depletion of the oncogenic signaling, coupled with a wide range of mutant coverage, TGRX-3247, as a targeted protein degrader, may potentially bring clinical benefits that are unseen with previous TKIs, including improved DMR, TFR rates, and even the possibility of functional cure. Its potential clinical application for CML patients is worth further investigation.
- |||||||||| Journal: IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat. (Pubmed Central) - Nov 4, 2024
In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.
- |||||||||| macozinone (PBTZ169) / Innovative Medicines for Tuberculosis, Nearmedic, Bill & Melinda Gates Foundation
Review, Journal: Advances in antibacterial agents for Mycobacterium fortuitum. (Pubmed Central) - Nov 4, 2024
Most compounds effective against M. fortuitum are synthetic, with macozinone, featuring a 2-piperazine-benzothiazinone framework, standing out as a notable drug candidate...Some compounds' mechanisms of action on M. fortuitum have been studied, including NITD-916, which acts as an enoyl-acyl carrier protein reductase inhibitor, and TBAJ-5307, which inhibits F-ATP synthase. Moreover, this review discusses the pathogenic molecular mechanisms and potential therapeutic targets within this mycobacterium.
- |||||||||| liproxstatin-1 / Jilin University
Journal: Inhibition of calpain reduces oxidative stress and attenuates pyroptosis and ferroptosis in Clostridium perfringens Beta-1 toxin-induced macrophages. (Pubmed Central) - Oct 31, 2024
In addition, the inhibition of ferroptosis using liproxstatin-1 inhibited the shriveled mitochondrial morphology, increased the expression of glutathione peroxidase 4, nicotinamide adenine dinucleotide (phosphate) hydrogen: quinone oxidoreductase 1 and cysteine/glutamic acid reverse transport solute carrier family 7 members 11, decreased the expression of heme oxygenase 1, nuclear receptor coactivator 4 and transferrin receptor proteins, reduced malondialdehyde and lipid peroxidation levels, and increased intracellular L-glutathione levels in cells treated with rCPB1...We showed that PD151746 inhibited ATP and ROS production, reversed the representative pyroptosis/ferroptosis indicators and subsequently reduced inflammation. The above findings indicate that rCPB1 might lead to macrophage pyroptosis and ferroptosis through the large and sustained increase in intracellular calpain and oxidative stress, further lead to inflammation.
- |||||||||| DCC-3116 / Ono Pharma
Review, Journal: A patent review of UNC-51-like kinase 1/2 inhibitors (2019-present). (Pubmed Central) - Oct 29, 2024
Despite the great success of ULK1/2 inhibitors development, ULK1/2 inhibitors are ATP competitive inhibitors of aminopyrimidines currently, and most ULK1/2 inhibitors are still in the preclinical research stage, with only DCC-3116 entered clinical research. Therefore, developing highly selective ULK1/2 inhibitors with low side effects and high bioavailability remains a challenging and promising research direction.
- |||||||||| Journal: Adenosine Triphosphate Inhibits Cold-Responsive Aggregation. (Pubmed Central) - Oct 15, 2024
A thorough comparison of ATP's cryoprotective activity with traditionally known biological cryoprotectants (glycine and betaine) reveals ATP's greater efficiency. In retrospect, our findings highlight ATP's additional biological role in cryopreservation, expanding its potential biomedical applications by offering effective protection of cells from cryoinjuries and avoiding the significant challenges associated with the toxicity of organic cryoprotectants.
- |||||||||| colistin sulphate / Generic mfg.
Journal: Inhibition of the ATP synthase increases sensitivity of Escherichia coli carrying mcr-1 to polymyxin B. (Pubmed Central) - Sep 26, 2024
Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments...In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection.
- |||||||||| Sirturo (bedaquiline) / J&J, Pharmstandard
Journal: Innovative Bedaquiline-Based Delivery Systems for Multidrug-Resistant Tuberculosis Treatment. (Pubmed Central) - Sep 21, 2024
However, the cost of the drug remains a concern, and efforts are underway to make bedaquiline more accessible and affordable to patients in resource-limited settings. Nevertheless, the development of bedaquiline nanofor-mulations represents a significant step forward in the fight against TB and offers hope to millions of patients across the globe.
- |||||||||| Journal: Dual feedback inhibition of ATP-dependent caffeate activation economizes ATP in caffeate-dependent electron bifurcation. (Pubmed Central) - Sep 18, 2024
This newly discovered mechanism contributes to our current understanding of ATP conservation during the caffeate-dependent electron-bifurcating pathway in the ecologically important acetogen Acetobacterium woodii. Bioinformatic mining of microbial genomes revealed contiguous genes homologous to carABC within the genomes of other anaerobes from various environments, suggesting this mechanism may be widely used in other CoA-dependent electron-bifurcating pathways.
- |||||||||| quemliclustat (AB680) / Arcus Biosci, Gilead
Journal, Immunogenic cell death: Interference of ATP-Adenosine Axis by Engineered Biohybrid for Amplifying Immunogenic Cell Death-Mediated Antitumor Immunotherapy. (Pubmed Central) - Sep 18, 2024
Particularly, the designed Bc@AZTF can actively enrich in tumor sites and respond to the acidic tumor microenvironment to offload AZTF nanoparticles, which can consume intracellular ATP (iATP) content and simultaneously inhibit the ATP-adenosine axis to reduce the accumulation of adenosine, thereby alleviating adenosine-mediated immunosuppression and strikingly amplifying ICD effect. Importantly, the synergy of anti-PD-1 (?PD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism.
- |||||||||| Journal: Conserved gatekeeper methionine regulates the binding and access of kinase inhibitors to ATP sites of MAP2K1, 4, and 7: Clues for developing selective inhibitors. (Pubmed Central) - Sep 15, 2024
These structural features provide clues for developing highly potent and selective inhibitors against MAP2Ks. Abbreviations: ATP, adenosine triphosphate; FDA, Food and Drug Administration; MAP2Ks, mitogen-activated protein kinase kinases; MD, molecular dynamics; NSCLC, non-small cell lung cancer; 5Z7O, 5Z-7-oxozeaenol; PDB, protein data bank; RMSD, root-mean-square deviation.
- |||||||||| Journal: Effects of polystyrene microplastic composite with florfenicol on photosynthetic carbon assimilation of rice (Oryza sativa L.) seedlings: Light reactions, carbon reactions, and molecular metabolism. (Pubmed Central) - Sep 7, 2024
The key enzymes involved in photorespiration, glycolate oxidase (GO) and catalase (CAT), responded positively, photosynthetic phosphorylation was inhibited, and ATP content and H+-ATPase activity were suppressed, nutrient content (K, P, N, Ca, Mg, Fe, Cu, Zn, Mn, and Ni) significantly affected. Transcriptomic analysis showed that FF and PS-MPs severely affected the photosynthetic capacity of rice seedlings, including photosystem I, photosystem II, non-photochemical quenching coefficients, and photosynthetic electron transport.
- |||||||||| Journal: The novel family of Warbicin (Pubmed Central) - Sep 6, 2024
cells and cancer cells reversibility is compromised, causing constitutively hyperactive glucose uptake and phosphorylation. Based on their chemical structure and properties, we suggest that Warbicin
- |||||||||| glibenclamide / Generic mfg.
Journal: Live Cell Monitoring of Phosphodiesterase Inhibition by Sulfonylurea Drugs. (Pubmed Central) - Aug 31, 2024
Using biochemical assays, we could also show that tolbutamide can inhibit PDE activity through an allosteric mechanism. Therefore, the cAMP-elevating capacity due to allosteric PDE inhibition in addition to direct Epac activation may contribute to the therapeutic effects of SU drugs.
- |||||||||| Journal: Structural basis for allosteric regulation of human phosphofructokinase-1. (Pubmed Central) - Aug 26, 2024
The T-state structure reveals conformational differences between the bacterial and eukaryotic enzyme, the mechanisms of allosteric inhibition by ATP binding at multiple sites, and an autoinhibitory role of the C-terminus in stabilizing the T-state. We also determine structures of PFKL filaments that define the mechanism of higher-order assembly and demonstrate that these structures are necessary for higher-order assembly of PFKL in cells.
- |||||||||| usnoflast (ZYIL1) / Zydus Lifesci
Preclinical, Journal: A novel selective NLRP3 inhibitor shows disease-modifying potential in animal models of Parkinson's disease. (Pubmed Central) - Aug 26, 2024
There were positive changes in the genes related to walking, locomotor activity, neurogenesis, neuroblast proliferation and neuronal differentiation in the PD brain indicating improvement in neural health which translated into improved mobility. These findings clearly indicate that selective NLRP3 inhibitor ZYIL1, ameliorates neuroinflammation and appears to have the potential for disease modification and progression associated with PD.
- |||||||||| cisplatin / Generic mfg.
Biomarker, Journal, Tumor microenvironment: Tumor microenvironment activation amplify oxidative stress promoting tumor energy remodeling for mild photothermal therapy and cuproptosis. (Pubmed Central) - Aug 21, 2024
Here, an H2S-responsive mesoporous Cu2Cl(OH)3-loading chemotherapeutic cisplatin (CDDP) was synthesized, and the final nanoparticle, CDDP@Cu2Cl(OH)3-CDs (CDCuCDs), was encapsulated by electrostatic action with carbon dots (CDs)...Down-regulated ATP inhibits heat shock protein expression, which promotes the therapeutic effect of mild photothermal therapy and reduces the efflux of intracellular copper ions, thus improving the therapeutic effect of cuproptosis. Our research provides a potential therapeutic strategy using overproduction H2S responses in tumors, allowing tumor microenvironment-activated
- |||||||||| Journal: Molecular basis of Gabija anti-phage supramolecular assemblies. (Pubmed Central) - Aug 15, 2024
Unexpectedly, the GajAB displays enhanced activity for plasmid DNA, suggesting a role of substrate selection by GajB. Together, our study defines a framework for understanding anti-phage immune defense by the GajAB complex.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: Ginsenoside Rg3 combined with near-infrared photothermal reversal of multidrug resistance in breast cancer MCF-7/ADR cells. (Pubmed Central) - Aug 14, 2024
Adriamycin (ADR) is a frequently employed chemotherapeutic agent for the management of breast cancer...This was achieved by reversing the expression of drug resistance-associated proteins, while also inhibiting cell proliferation, migration, and epithelial-mesenchymal transition (EMT) processes via attenuation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway transduction. Ginsenoside Rg3 combined with near-infrared photothermal therapy (NIR) effectively reverses multidrug resistance in breast cancer MCF-7/ADR cells, providing a new therapeutic strategy for breast cancer drug resistance.
- |||||||||| Journal: A novel ABCC9 variant in a Greek family with Cantu syndrome affecting multiple generations highlights the functional role of the SUR2B NBD1. (Pubmed Central) - Jul 20, 2024
The membrane potential in cells stably expressing hKir6.1 and hSUR2B with p.Gly814Trp was hyperpolarized compared to cells expressing WT channels, and inside-out patch-clamp assays of KATP channels formed with hSUR2B p.Gly814Trp demonstrated a decreased sensitivity to ATP inhibition, confirming a relatively mild GOF effect of this variant. The specific location of the variant reveals an unrecognized functional role of the first glycine in the signature motif of the nucleotide binding domains in ATP-binding cassette (ABC) protein ion channels.
- |||||||||| Xalkori (crizotinib) / Pfizer
Review, Journal, BRCA Biomarker, PARP Biomarker: Overcoming Chemoresistance in Cancer: The Promise of Crizotinib. (Pubmed Central) - Jul 13, 2024
In summary, crizotinib exerts anti-tumor effects through several mechanisms, including the inhibition of kinases and the restoration of drug sensitivity. The potential of crizotinib in combination therapies is emphasized, particularly in cancers with a high prevalence of the p53 mutant, such as triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC).
- |||||||||| Review, Journal: Mechanisms and Functions of Sweet Reception in Oral and Extraoral Organs. (Pubmed Central) - Jul 13, 2024
Additionally, sweet receptors may have unique roles in certain organs like the trachea and bone. This review summarizes past and recent studies on sweet receptor systems, exploring the molecular mechanisms and physiological functions of sweet (sugar) detection in both oral and extraoral organs.
- |||||||||| bedaquiline analogue (TBAJ-587) / Global Alliance for TB Drug Development
Journal: Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587. (Pubmed Central) - Jul 10, 2024
The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase
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