K-312 / Kowa - LARVOL DELTA

ASH2L-K312-Lac Stimulates Angiogenesis in Tumors to Expedite the Malignant Progression of Hepatocellular Carcinoma. (PubMed, Adv Sci (Weinh)) - "Finally, clinical sample analyses and robust in vivo preclinical experiments identify ASH2L-K312-lac as a promising therapeutic target for clinical application. These findings provide a theoretical foundation for the clinical translation of ASH2L-K312-lac-based treatment approaches, offering potential advancements in HCC diagnosis and treatment."

Journal • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Oncology • Solid Tumor • AARS1 • HDAC1

MECHANISMS OF ATP2B1 LACTYLATION AFFECTING CA2+ HOMEOSTASIS TO PROMOTE METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (DDW 2025) - "Treatment of cells with a targeted mutant ATP2B1 plasmid revealed that the K312 locus of ATP2B1 could ameliorate hepatic steatosis and hepatic lipid peroxidation by stabilizing Ca 2+ homeostasis in the PA-induced MASLD cell model...Conclusion Taken together, an imbalance of lactate metabolism affects the lactate modification of ATP2B1. This, in turn, affects Ca 2+ homeostatic remodeling to promote the progression of MASLD, providing a theoretical basis for targeting MASLD therapy to ATP2B1."

Hepatocellular Cancer • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor

Performance Correction and Parameters Identification Considering Non-Uniform Electric Field in Cantilevered Piezoelectric Energy Harvesters. (PubMed, Sensors (Basel)) - "It is found that the relative corrections to traditional model have nothing to do with the absolute dimensions of the harvesters, but only relate to three dimensionless parameters, i.e., the ratio of the elastic layer's to the piezoelectric layer's thickness; the ratio of the elastic modulus of the elastic layer to the piezoelectric layer; and the piezoelectric materials' electromechanical coupling coefficient squared, k312...An inverse problem to identify the material parameters based on experimentally obtained power output performance is also investigated. The results show that the accuracy of material parameters identification is improved when considering a non-uniform electric field."

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Functional Coupling of ANXA1 and KCa3.1 Attenuated Renal Tubulointerstitial Fibrosis in Diabetic Kidney Disease (KIDNEY WEEK 2023) - "SUMOylation sites were predicted by SUMOsp2.0, and ANXA1 lysine residues K113, K161, K185, K257 and K312 were mutated to test the relative site change. Our study suggests that ANXA1-KCa3.1 functional coupling may be a promising therapeutic strategy to mitigate DKD-induced TIF."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • ANXA1 • FN1 • KCNN4 • TGFB1

GATA-1 Acetylation Negatively Regulates Erythroid Differentiation (ASH 2022) - "Key GATA-1 acetylation sites at K245, K246, K312, K314, K315 were mutated to acetyl-mimicking glutamine (KQ), non-acetyl-mimicking arginine (KR) or mutated to nonpolar amino acid alanine (KA) in mouse erythroid progenitor G1E cells...Interestingly, KQ mutation also does not affect interaction with bromodomain proteins, including BRD3, BRD4 and BRD7, suggesting the acetylated epitope is not required for GATA-1 to interact with these bromodomain proteins. In summary, our study shows GATA-1 acetylation negatively regulates transcriptional activity that control erythroid commitment and differentiation."

Anemia • Hematological Disorders • Thrombocytopenia • BRD3 • BRD4 • DDX17 • GATA1 • HDAC1 • LMO2 • RUNX1

P301S-hTau acetylates KEAP1 to trigger synaptic toxicity via inhibiting NRF2/ARE pathway: A novel mechanism underlying hTau-induced synaptic toxicities. (PubMed, Clin Transl Med) - "P301S-hTau could acetylate KEAP1 to trigger synaptic toxicity via inhibiting the NRF2/ARE pathway. These findings provide a novel and potential target for the therapeutic intervention of tauopathies."

Journal • Mood Disorders • Psychiatry • Targeted Protein Degradation • KEAP1 • Napsin A

Protons in Gating the Kv1.2 Channel: A Calculated Set of Protonation States in Response to Polarization/Depolarization of the Channel, with the Complete Proposed Proton Path from Voltage Sensing Domain to Gate. (PubMed, Membranes (Basel)) - "In the deprotonated state for K312, a low energy state, our calculations come close to reproducing the X-ray structure...The coupling of the paths to the VSD, and to the PVPV section that essentially forms the gate, can be easily seen from the results of the calculation. The gate itself remains for further computations."

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Development of antiviral carbon quantum dots that target the Japanese Encephalitis Virus envelope protein. (PubMed, J Biol Chem) - "The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections."

Journal • CNS Disorders • Infectious Disease

Acetylation of ANXA1 reduces caspase-3 activation by enhancing the phosphorylation of caspase-9 under OGD/R conditions. (PubMed, Cell Signal) - "The lysine 312 residue (K312) was selected as the target site in ANXA1 because it is associated with SIRT2, and its mimic (K312Q) and silent (K312R) mutants were then established through site mutagenesis...In this process, K312Q ANXA1 was found to be directly associated with PRKAR2B, diminishing its restriction on the catalytic subunit of PKA. In conclusion, acetylated ANXA1 can promote the phosphorylation of caspase-9 to decrease the activation of caspase-3 by enhancing the expression of a kinase upstream of caspase-9 after the OGD/R stimulation."

Journal • ANXA1 • CASP3 • CASP9

Design of Bacillus fastidious Uricase Mutants Bearing Long Lagging Phases Before Exponential Decreases of Activities Under Physiological Conditions. (PubMed, Protein J) - "Within 1.5 nm from the α-carboxyl group of the last leucine (L322), E30, K26, D257, R258, E311, K312 and E318 from the same monomer plus D126 and K127 from a monomer of the other homodimer generate an electrostatic interaction network...Under physiological conditions, the mutant V144A/Y319R showed an approximately 4 week lagging phase before the exponential activity decrease, an apparent half-life of activity nearly three folds of mutant V144A, but comparable activity. The introduction of ionizable residues into the C-terminus contacting the other homodimer for additional and/or stronger electrostatic attractions between homodimers may be a universal approach to thermostable mutants of uricases."

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Rapid progressive lung cancers harbouring multiple clonal driver mutations with big bang evolution model. (PubMed, Cancer Genet) - "We should pay attention to clinical course of lung cancer patients harboring multiple clonal driver mutations in their primary lesions. Their punctuated and big bang evolutionary process could develop systemic clinically undetectable metastases with an unexpected speed."

Journal • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Positron Emission Tomography (PET) Imaging Study to Investigate the Biodistribution and Clearance of an Albumin Binding Domain Antibody (AlbudAb) GSK3128349 in Healthy Male Subjects (clinicaltrials.gov) - P1; N=6; Recruiting; Sponsor: GlaxoSmithKline; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar

A Monoclonal Antibody Specific for Japanese Encephalitis Virus with High Neutralizing Capability for Inclusion as a Positive Control in Diagnostic Neutralization Tests. (PubMed, Am J Trop Med Hyg) - "To develop a reproducible positive control antibody useable in diagnosis of JEV infections, murine hybridomas were developed from mice inoculated with a combination of IXIARO JEV vaccine and JEV domain III of the envelope protein (E-DIII). The functional epitopes were mapped using virus neutralization escape variants to amino acid residues S309, K312, and G333 in E-DIII. This MAb may be substituted for human immune sera used as a positive control in PRNT for distribution to public health laboratories worldwide in potential future outbreaks of JEV."

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