diazepinomicin (AMO-01) / AMO Pharma, GSK - LARVOL DELTA

An integrated theoretical study on natural alkaloids as SARS-CoV-2 main protease inhibitors: a step toward discovery of potential drug candidates with anti-COVID-19 activity. (PubMed, RSC Adv) - "Docking experiments were then performed on the selected compounds, and the top three compounds with the highest docking scores were identified as diazepinomicin, (+)-N-methylisococlaurine, and hymenocardine-H...MD simulations were also performed to check the flexibility, stability and compactness of these complexes for revalidation of docking scores. finally, ADMET experiments revealed that (+)-N-methylisococlaurine exhibited the most favourable properties among these three compounds."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

An open-label study evaluating the safety and efficacy of AMO-01 for the treatment of seizures in Phelan-McDermid syndrome. (PubMed, HGG Adv) - "These results provide preliminary support for the safety of AMO-01 and its efficacy in reducing seizures in adults with PMS. Future placebo-controlled studies with larger sample sizes and repeated dosing are warranted."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Psychiatry

Bioinsecticidal activity of actinomycete secondary metabolites against the acetylcholinesterase of the legume's insect pest Acyrthosiphon pisum: a computational study. (PubMed, J Genet Eng Biotechnol) - "In addition to its favorable pharmacokinetic properties, the special chemical structure of diazepinomicin allows this molecule to interact intensely with AChE notably through the involvement of its two groups farnesyl diphosphate and dibenzodiazepinone which ensure several hydrogen and hydrophobic interactions, that offers very high stability to the complex AChE diazepinomicin. In conclusion, diazepinomicin can be suggested as a potential bioinsecticidal agent against the pest A. pisum."

Journal • Pain

Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study. (PubMed, Metabolites) - "The results indicated that four compounds, Phenalinolactones A-D, BU-4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the agr quorum sensing system and hemolytic activity of S. aureus...Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of S. aureus AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors."

Journal • Preclinical • Infectious Disease

Synthesis and biological evaluation of BU-4664L derivatives as potential anticancer agents. (PubMed, Bioorg Med Chem Lett) - "All of the derivatives displayed micromolar activity against the human prostate cancer PC-3 cells, while lower or no activity against the human lung H460 cells. The most active derivatives were 10a and 16c which exerted antiproliferative activity against PC-3 cells with GI values of 5.66 and 5.94 μM, respectively, and thus represent promising lead compounds for further development."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[VIRTUAL] AMO Pharma (BIO 2021) - "3 clinical stage assets: AMO-02 in Phase III in Myotonic Dystrophy AMO-01 in Phelan McDermid Syndrome AMO-06 in Rett syndrome and Combat PTSD"

CNS Disorders • Developmental Disorders • Genetic Disorders • Movement Disorders • Muscular Dystrophy • Myotonic Dystrophy • Post-traumatic Stress Disorder

AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy (clinicaltrials.gov) - P2; N=6; Completed; Sponsor: Alexander Kolevzon; Recruiting ➔ Completed; N=10 ➔ 6

Enrollment change • Trial completion • CNS Disorders • Epilepsy

AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy (clinicaltrials.gov) - P2; N=10; Recruiting; Sponsor: Alexander Kolevzon; Trial completion date: Jul 2020 ➔ Jul 2021; Trial primary completion date: Jul 2020 ➔ Jul 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential of a Lake Michigan Actinomycete. (PubMed, J Nat Prod) - "Five known BGCs were identified encoding desferrioxamine, alkyl- O-dihydrogeranylmethoxyhydroquinone, a spore pigment, sioxanthin, and diazepinomicin, which is currently in phase II clinical trials to treat Phelan-McDermid syndrome and co-morbid epilepsy...B006 that will contribute to deorphaning BGCs in the future. This study is one of the few attempts to report the biosynthetic capacity of a freshwater-derived actinomycete and highlights this resource as a potential reservoir for new natural products."

Journal

AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy (clinicaltrials.gov) - P2; N=10; Recruiting; Sponsor: Alexander Kolevzon; Trial completion date: Jul 2019 ➔ Jul 2020; Trial primary completion date: Jul 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date

Whole Genome Sequencing and Metabolomic Study of Cave Streptomyces Isolates ICC1 and ICC4. (PubMed, Front Microbiol) - "...Spectral analysis clearly identified a number of diketopiperazine products through matched reference spectra for cyclo (Leu-Pro), cyclo (Pro-Val) and cyclo [(4-hydroxyPro)-Leu]. One of the terpenes gene clusters predicted by antiSMASH possesses a seven-gene pathway consistent with diazepinomicin biosynthesis...The predicted similarities in molecule production and genome shared by these two strains could be an indicative of a cooperative mode of living in extreme habitats instead of a competitive one. This secondary metabolite potential may contribute to the fitness of ICC1 and ICC4 in the Iron Curtain Cave."

Journal

AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy (clinicaltrials.gov) - P2; N=10; Recruiting; Sponsor: Alexander Kolevzon; Trial completion date: Mar 2019 ➔ Jul 2019; Trial primary completion date: Mar 2019 ➔ Jul 2019

Clinical • Trial completion date • Trial primary completion date