R 348 / Rigel Pharmaceuticals - LARVOL DELTA

Cancer Patient Experience of Uncertainty While Waiting for Genome Sequencing Results. (PubMed, Front Psychol) - "Greater perceived susceptibility for cancer [r(348) = 0.14, p < 0.01], fear of cancer recurrence [r(348) = 0.19, p < 0.01], perceived importance of genome sequencing [r(350) = 0.24, p < 0.01], intention to change behavior if a gene variant indicating risk is found [r(349) = 0.29, p < 0.01], perceived ability to cope with results [r(349) = 0.36, p < 0.01], and satisfaction with decision to have genome sequencing [r(350) = 0.52, p < 0.01] were significantly correlated with negative attitudes towards uncertainty at baseline...This study demonstrates the complexity of uncertainty generated by genome sequencing for cancer patients and provides further support for the inter-relationship between uncertainty and anxiety. Helping patients manage their uncertainty may ameliorate psychological morbidity."

Clinical • Journal • Mood Disorders • Oncology • Psychiatry

Characterizing an allosteric inhibitor-induced inactive state in with-no-lysine kinase 1 using Gaussian accelerated molecular dynamics simulations. (PubMed, Phys Chem Chem Phys) - "The outward movement of the αC-helix breaks the salt-bridge between Glu268 and R348 and renders the kinase domain inactive. Overall, our study provides detailed insights into the inhibitor-induced allosteric mechanisms and may help design specific allosteric inhibitors against WNK1 for treating hypertension."

Journal • Hypertension

Novel Splicing Variant in the PMM2 Gene in a Patient With PMM2-CDG Syndrome Presenting With Pericardial Effusion: A Case Report. (PubMed, Front Genet) - "The novel variant was predicted to result in loss of donor splice site, and the analysis at mRNA level confirmed that it leads to exon five skipping (r.348_447del) and causes premature termination of translation to the protein (p.G117Kfs4), therefore is classified as likely pathogenic. Although there is no curative therapy for the PMM2-CDG at the moment, the other supportive care options are available to be offered. The definite diagnosis of PMM2-CDG can also assist in the process of genetic counseling, family planning, and preimplantation genetic diagnosis."

Clinical • Journal • Cardiovascular • Hematological Disorders

Colistin Resistance in Environmental Isolates of Acinetobacter baumannii. (PubMed, Microb Drug Resist) - "In silico genome analysis revealed nucleotide variations resulting in amino acid changes in LpxC (N286D), LpxD (E117K), PmrB (A138T, R263S, L267W, Q309P, and A444V), and EptA (F166L, I228V, R348K, A370S, and K531T)...Isolates expressed low hydrophobicity, biofilm, and pellicle formation, but showed excellent survival in river water during 50 days of monitoring. Colistin- and pandrug-resistant A. baumannii disseminated in the environment could represent the source for the occurrence of serious community-acquired infections."

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Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy. (PubMed) - Genet Test Mol Biomarkers - "Our findings expand the mutational spectrum of FEVR in the Indian population and provide some guidelines in clinical diagnosis."

Journal • Biosimilar

Rigel to focus on ITP, DLE and dry eye (Rigel Press Release) - P2, N=54; Sponsor: Rigel; SKINDLE (NCT01597050); P2, N=210; Sponsor: Rigel; DROPS (NCT01900249); "Rigel's other two lead programs, R333, a topical dermatological JAK/SYK inhibitor for discoid lupus erythematosus, and R348, a topical ophthalmic JAK/SYK inhibitor for dry eye, are presently in Phase 2 studies, with results expected in Q4 2013 and Q2 2014, respectively. Rigel expects to advance one of these two molecules into a Phase 3 clinical program by 2014/15."

Anticipated new P3 trial • Anticipated P2 data • Immunology • Lupus

R348 did not meet endpoints in phase 2 dry eye study (Rigel Press Release) - P2, N=206; Sponsor: Rigel  NCT01900249; "Rigel...announced that R348, its ophthalmic JAK/SYK inhibitor, did not meet the primary or secondary endpoints in a recently completed Phase 2 clinical study in patients with dry eye disease.  The endpoints were measured by changes in corneal fluorescein staining, conjunctival staining, tear production and dry eye symptom scores from baseline over 12 weeks of treatment versus placebo....Rigel has decided not to initiate any new studies of R348 for this indication..."

P2 data • Immunology

A Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-associated Ocular Surface Disease (ARVO 2017) - "Purpose:Janus Kinase (JAK) and Spleen Tyrosine Kinase (SYK) play critical functions in T cell activation and in inflammation. This Phase 2, randomized trial indicates that 0.5% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated and has some therapeutic efficacy in treating ocular GVHD. Larger trials are required to derive more definitive data."

Clinical • Biosimilar • Dry Eye Disease • Graft versus Host Disease • Immunology • Ophthalmology

Rigel: Investor Day (Rigel) - Anticipated P2 trial completion for dry eye disease in Q3 2014; Anticipated P2 trial completion for ocular GvHD in Q2 2016

Anticipated trial completion date • Immunology

Rigel: J.P.Morgan Healthcare Conference (Rigel) - Anticipated data from P2 trial (NCT02040623) for dry eye in GvHD in 2016

Anticipated P2 data • Immunology

Rigel announces fourth quarter and year end 2011 financial results (Rigel) - In Q4 2011, Rigel initiated P1 clinical studies of R548 with a focus on its potential to treat transplant rejection & other immune system disorders; R548 is expected to moderate the immune system's response to the allograft and improve patient outcomes; Rigel is developing R348 for topical ophthalmic use to treat Sjogren's syndrome; Sjogren's affects nearly four million Americans, & present therapies for this chronic & painful condition are only minimally effective; Rigel plans to initiate P1 clinical studies with R348 by end of 2012

Anticipated P1 trial initiation • Immunology

Rigel: Investor Day (Rigel) - Anticipated top-line results from P2 trial for dry eye disease in H2 2014

Anticipated P2 data • Immunology

Safety and Efficacy Study of R932348 Ophthalmic Solution in Chronic Ocular Graft Versus Host Disease Patients(DROPS-2) (clinicaltrials.gov) - P2; N=30; Completed; Sponsor: Rigel Pharmaceuticals; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Dry Eye Disease • Graft versus Host Disease • Immunology • Ocular Inflammation • Ophthalmology

A safety, tolerability and pharmacokinetics study of R932348 eye drops in patients with dry eye disease (clinicaltrials.gov) - P1, N=36; Sponsor: Rigel Pharmaceuticals; Recruiting; New P1 trial.

New P1 trial • Immunology

Novel haplotype combinations reveal enhanced seedling vigor traits in rice that can accurately predict dry biomass accumulation in seedlings. (PubMed, Breed Sci) - "One combination, haplotype II-1 (RM317 (I/II) and RM348 (1/2)), consistently produced superior values for seedling height, root length, and leaf length. The new prediction tool for seedling dry weight, namely the haplotype of RM317 and RM348, will have a wide range of applications in breeding strategies by using marker-assisted selection to produce elite lines that optimize genetic composition contributing to seedling vigor."

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Cloning and expression analysis of squalene epoxidase genes from Siraitia grosvenorii (PubMed, Zhongguo Zhong Yao Za Zhi) - "...The docking results showed that predicted proteins of SgSQE1 and SgSQE2 can interact with OS, with different contact sites (R348 for SgSQE1, H349 for SgSQE2)...However, all the results strongly suggested that SgSQEs were both involved in secondary metabolites biosynthesis in S. grosvenorii. SgSQE1 might be involved in mogrosides biosynthesis and SgSQE2 might participate in other cucurbitane-type triterpenes or phytosterols biosynthesis."

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