R 343 / Rigel - LARVOL DELTA

Unnatural Amino Acid Photo-Crosslinking Sheds Light on Gating of the Mechanosensitive Ion Channel OSCA1.2. (PubMed, Int J Mol Sci) - "Targeted UV-induced crosslinking at positions F22, H236, and R343 locked the channel in a non-conducting state, indicating their functional relevance...Together, these results support a model in which mechanical gating involves a distributed network of residues across multiple channel regions, allosterically converging on the activation gate. This study expands our understanding of mechanotransduction by revealing how distant structural elements contribute to force sensing in OSCA channels."

Journal

THE EFFECTS OF GLYCYRRHIZA GLABRA EXTRACT IN HIGH-FAT DIET-INDUCED OBESE MALE MICE: A CONTROLLED EXPERIMENTAL STUDY (ASPIRE 2024) - "Then, we divided mice into 4 groups (NFD, HFD, RG343, RG686) with 12 mice/group... Following the intervention, mice exhibited reduced weight, weight gain, BMI, and waist circumference. However, there was no difference between the 2 doses. Moreover, blood glucose, visceral fat mass, total cholesterol, and LDL-c levels of mice after the intervention were lower."

Preclinical • Genetic Disorders • Obesity

Loop 6 and the β-hairpin flap are structural hotspots that determine cofactor specificity in the FMN-dependent family of ene-reductases. (PubMed, FEBS J) - "Initial docking results indicated that the arginine triad R283, R343, and R366 residing on and close to a critical loop at the active site (loop 6) are the main contributors to NADPH binding...We postulate that cofactor specificity is determined by the arginine triad/loop 6 and the residue(s) controlling access to a hydrophobic cleft formed by the β-hairpin flap. Thus, NADPH preference depends on a properly positioned arginine triad, whereas granting access to the hydrophobic cleft at the β-hairpin flap favors NADH binding."

Journal

High-quality genomes of Paenibacillus spp. RC334 and RC343, isolated from a long-term forest soil warming experiment. (PubMed, Microbiol Resour Announc) - "Both genomes were 5.98 Mb and assembled as a single contig. We describe the assembly and annotation of the two high-quality draft genomes for these isolates here."

Journal

The crystal structure of a simian Foamy Virus receptor binding domain provides clues about entry into host cells. (PubMed, Nat Commun) - "In this work we present the X-ray structure of the receptor binding domain (RBD) of a simian FV Env at 2.57 Å resolution, revealing two subdomains and an unprecedented fold. We have generated a model for the organization of the RBDs within the trimeric Env, which indicates that the upper subdomains form a cage-like structure at the apex of the Env, and identified residues K342, R343, R359 and R369 in the lower subdomain as key players for the interaction of the RBD and viral particles with heparan sulfate."

Journal • Human Immunodeficiency Virus • Infectious Disease

Probiotics Exhibit Strain-Specific Protective Effects in T84 Cells Challenged With Clostridioides difficile-Infected Fecal Water. (PubMed, Front Microbiol) - "ProtecFlor™, Lactobacillus helveticus R0052, and Bifidobacterium longum R0175 showed moderate effectiveness, and L. rhamnosus GG R0343 along with the two other multi-strain combinations were the least effective. Overall, the findings showed that probiotic strains possess the capability to modulate the CDI-mediated inflammatory response in the gut lumen."

Journal • Gastroenterology • Gastrointestinal Disorder • Immune Modulation • Immunology • Infectious Disease • Inflammation • Oncology • CXCL5 • IL32 • TNFA

Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases. (PubMed, Expert Opin Investig Drugs) - "The search terms used were SYK inhibitors, R406, fostamatinib (R788), P505-15 (PRT062607), entospletinib (GS-9973), R112, lanraplenib (GS-9876), cerdulatinib, R343, BAY-61-3606, GSK compound 143 (GSK143), R211, SKI-G-618, SKI-O-85, ER-27319, YM193306, RO9021 in conjunction with autoimmune disease using electronic databases including PubMed, EMBASE, MEDLINE and Google Scholar. However, the difficulties in developing highly selective SYK inhibitors and the unknown effects are challenges. Long term and real-world data are essential to determine the risk-benefit ratio and true role of SYK inhibitors in the therapy of ADs."

Journal • Immunology • Inflammation • SYK

Insights into the roles of charged residues in substrate binding and mode of action of mannuronan C-5 epimerase AlgE4. (PubMed, Glycobiology) - "Our results indicate that the charge pair R343-D345 might be directly involved in conformational changes of a loop that can be important for binding and dissociation. The computational and experimental approaches used in this study complement each other, allowing for a better understanding of individual residues' roles in binding and movement along the alginate chains."

Journal

Cowen Global Annual Healthcare Conference (Rigel) - Rigel anticipates inititiation of P2 trial in allergic asthma in 2012 and completion by 2013

Anticipated P2 trial completion • Anticipated P2 trial initiation • Immunology

Rigel announces fourth quarter and year end 2011 financial results (Rigel) - Rigel resumed responsibility for R343 following closure of Pfizer's allergy & respiratory development programs in 2011; Based on its MOA, this inhaled SYK inhibitor is expected to provide a new treatment paradigm for largest group of patients with allergic asthma whose symptoms range from acute to chronic phases of disease; Rigel expects to initiate a P2 clinical study with R343 for the treatment of allergic asthma in summer 2012

Anticipated P2 study • Immunology

Jefferies Global Healthcare Conference (Rigel) - P1b data

P1b data • Asthma

Rigel announces first quarter 2012 financial results (Rigel) - Rigel reported financial results for Q1 2012; Rigel reported total operating expenses of $24.1M in Q1 2012 vs. $20.9M in Q1 2011; increase in operating expenses was primarily due to the increase in research and development expenses in Rigel's clinical research programs; Largest increase was related to R343, an inhaled SYK inhibitor for asthma, that is expected to commence a P2 clinical trial this summer

Anticipated P2 trial initiation • Immunology

Microsecond molecular dynamics simulations and dynamic network analysis provide understanding of the allosteric inactivation of GSK3β induced by the L343R mutation. (PubMed, J Mol Model) - "Furthermore, network analysis identified the allosteric pathway from R343 to the primed phosphate binding site in the L343R mutant. Collectively, the results of this study provide a mechanistic explanation of how the L343R mutation allosterically affects the functional activity of GSK3β, which contributes to our understanding of GSK3β biology."

Journal

Functional Analysis of VDR Gene Mutation R343H in A Child with Vitamin D-Resistant Rickets with Alopecia. (PubMed, Sci Rep) - "Simulation models revealed the vanished interaction between guanidinium group of R343 and carboxyl group of E269. Without affecting the expression, conformation, nuclear location of VDR or heteridimerization with RXR, VDR-R343H impairs the transactivation activity of VDR on downstream transcription, accounting for HVDRR features with alopecia."

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