Q301 / Qurient - LARVOL DELTA

Q301P mutant of Vibrio PR protease affects activities under low-temperature and high-pressure conditions. (PubMed, J Biosci Bioeng) - "The homology models of PR protease suggested that the side chain of Q301 was hydrogen-bonded with the carbonyl oxygen atom of the main chain of N234 in the wild-type enzyme, and P301 had no contact with N234 in 10C9. The break of the hydrogen bond in 10C9 might strengthen the increase of the flexibility of the β-sheet near the substrate binding pocket under high-temperature conditions, whereas the flexibility of the β-sheet in 10C9 might be moderately increased compared to that in the wild-type enzyme under high-pressure conditions."

Journal

The Interaction of Munc18-1 Helix 11 and 12 with the Central Region of the VAMP2 SNARE Motif Is Essential for SNARE Templating and Synaptic Transmission. (PubMed, eNeuro) - "Residue Q301 in helix 11 plays a pivotal role in VAMP2 binding and template complex formation...This requires the correct assembly of the molecular membrane fusion machinery, N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, by Sec1/Munc18 proteins. In this study, we establish a map with single amino acid precision of how Munc18-1 provides a template for the binding of the v-SNARE protein VAMP2 and demonstrate its relevance for synaptic function."

Journal

Pediatric Primary Adrenal Insufficiency: A 21-year Single Center Experience. (PubMed, J Clin Res Pediatr Endocrinol) - "We determined etiologies in 86.3% of children with non-CAH PAI through specific clinical and laboratory findings with/without molecular analysis of candidate genes. ALD was the most common etiology. Nowadays, advanced molecular analyse can be utilized to establish a specific genetic diagnosis of PAI for patients who have no specific diagnostic features."

Clinical • Journal • Cardiovascular • Endocrine Disorders • Fatigue • Heart Failure • Hypoglycemia • Immunology • Nephrology • Pediatrics • Renal Disease • CYP17A1

Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly. (PubMed, EMBO J) - "Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18-1/syntaxin-1 complex and the MUN domain...This interaction ensures Munc18-1 to persistently associate with syntaxin-1 during the conformational change of syntaxin-1 from closed to open, which reinforces the role of Munc18-1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly."

Journal

Safety and Efficacy Study of Q301 in Mild to Moderate Adolescents and Adults Atopic Dermatitis Patients (clinicaltrials.gov) - P2; N=258; Completed; Sponsor: Qurient Co., Ltd.; Recruiting ➔ Completed

Clinical • Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology • Inflammation

Safety and Efficacy Study of Q301 in Mild to Moderate Adolescents and Adults Atopic Dermatitis Patients (clinicaltrials.gov) - P2; N=240; Recruiting; Sponsor: Qurient Co., Ltd.; Trial primary completion date: Oct 2019 ➔ Feb 2020

Trial primary completion date

Q301 (Zileuton) Cream Demonstrates Superiority to Vehicle in Improving Atopic Dermatitis: Results From a Phase 2A Trial (AAD 2019) - "Zileuton is an inhibitor of 5-lipoxygenase, an enzyme that catalyzes the conversion of arachidonic acid to leukotrienes, which contribute to atopic inflammation. Local tolerability was generally good, with 3 subjects discontinuing treatment (one Q301 cream, two vehicle) with observed application site pain, pruritus and erythema. The results from this Phase 2A study suggest that Q301 Cream 1.0% appears to be a promising noncorticosteroidal topical agent that being developed for treating AD."

Head-to-Head • P2a data

Qurient unveils P2a trial results for atopic dermatitis treatment in US (Korea Biomedical Review) - P2a, N=57; NCT02426359; Sponsor: Qurient; "Phase 2a clinical trials, conducted in the United States, showed that 30 percent of patients receiving Q301 had their symptoms improve, compared to the 4 percent from the control group. Also, the treatment had similar side effects when compared with the control group."

P2a data

A Study To Evaluate the Long-Term Safety, Tolerability and Effect on Disease Course (clinicaltrials.gov) - P3; N=839; Terminated; Sponsor: Teva Pharmaceutical Industries, Ltd.; N=472 ➔ 839

Clinical • Enrollment change