Marine mangrove vegetation has been traditionally employed in folk medicine to address various ailments. Notably, Rhizophora apiculata Blume has exhibited noteworthy properties, demonstrating efficacy against cancer, viruses, and bacteria. The enzyme fatty acid synthase (FAS) plays a pivotal role in de novo fatty acid synthesis, making it a promising target for combating colon cancer. Our study focused on evaluating the FAS inhibitory effects of both the crude extract and three isolated compounds from R. apiculata. The n-butanol fraction of R. apiculata extract (BFR) demonstrated a significant inhibition of FAS, with an IC50 value of 93.0 µg/mL. For inhibition via lyoniresinol-3α-O-β-rhamnopyranoside (LR), the corresponding IC50 value was 20.1 µg/mL (35.5 µM). LR competitively inhibited the FAS reaction with acetyl-CoA, noncompetitively with malonyl-CoA, and in a mixed manner with NADPH. Our results also suggest that both BFR and LR reversibly bind to the KR domain of FAS, hindering the reduction of saturated acyl groups in fatty acid synthesis. Furthermore, BFR and LR displayed time-dependent inhibition for FAS, with kobs values of 0.0045 min−1 and 0.026 min−1, respectively. LR also exhibited time-dependent inhibition on the KR domain, with a kobs value of 0.019 min−1. In human colon cancer cells, LR demonstrated the ability to reduce viability and inhibit intracellular FAS activity. Notably, the effects of LR on human colon cancer cells could be reversed with the end product of FAS-catalyzed chemical reactions, affirming the specificity of LR on FAS. These findings underscore the potential of BFR and LR as potent FAS inhibitors, presenting novel avenues for the treatment of human colon cancer.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The Inhibitory Effects of Maclurin on Fatty Acid Synthase and Adipocyte Differentiation

Article

作者: Lee, Jiyun ; Lee, Bonggi ; Hwang, Ji Young ; Ryu, Heeyeon ; Baek, Jiwon ; Kim, Jae-Il ; Jeong, Hyeon Hak

Obesity is a complex health condition characterized by excessive adipose tissue accumulation, leading to significant metabolic disturbances such as insulin resistance and cardiovascular diseases. Fatty acid synthase (FAS), a key enzyme in lipogenesis, has been identified as a potential therapeutic target for obesity due to its role in adipocyte differentiation and lipid accumulation. This study employed a multidisciplinary approach involving in silico and in vitro analyses to investigate the anti-adipogenic properties of maclurin, a natural phenolic compound derived from Morus alba. Using SwissDock software (ChEMBL version 23), we predicted protein interactions and demonstrated a high probability (95.6%) of maclurin targeting FAS, surpassing the interaction rates of established inhibitors like cerulenin. Docking simulations revealed maclurin’s superior binding affinity to FAS, with a binding score of −7.3 kcal/mol compared to −6.7 kcal/mol for cerulenin. Subsequent in vitro assays confirmed these findings, with maclurin effectively inhibiting FAS activity in a concentration-dependent manner in 3T3-L1 adipocytes, without compromising cell viability. Furthermore, maclurin treatment resulted in significant reductions in lipid accumulation and the downregulated expression of critical adipogenic genes such as PPARγ, C/EBPα, and FAS, indicating the suppression of adipocyte differentiation. Maclurin shows potential as a novel FAS inhibitor with significant anti-adipogenic effects, offering a promising therapeutic avenue for the treatment and prevention of obesity.

项与 Gene Therapy Fas Inhibitor(ONL) 相关的新闻（医药）

2024-09-10

·GlobeNewswire-Health Care

ONL Therapeutics to Present at the 57th Annual Scientific Meeting of The Retina Society and EURETINA Innovation Spotlight

ANN ARBOR, Mich., Sept. 10, 2024 (GLOBE NEWSWIRE) -- ONL Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapies for protecting the vision of patients with retinal disease, today announced that the company plans to present clinical data at the upcoming 57th Annual Scientific Meeting of The Retina Society and EURETINA Innovation Spotlight (EIS). The Retina Society Meeting is scheduled for September 11-15, 2024, at the Four Seasons Hotel Ritz Lisbon in Lisbon, Portugal, while the EIS Meeting will take place September 18, 2024, at the International Barcelona Convention Center (CCIB) in Barcelona, Spain. Details of the Retina Society Meeting presentations are as follows: Title:Fas Inhibition with ONL1204 for the Treatment of Geographic Atrophy: Results from a Phase 1b StudyPresenter:Lejla Vajzovic, M.D.Associate Professor of OphthalmologyDuke University Eye CenterTime/Date:10:44 a.m. Western European Summer Time (WEST) on Saturday, September 14, 2024 Title:FAS Inhibition with Intravitreal ONL1204 for the Treatment of Macula-off Rhegmatogenous Retinal Detachment: Results from a Phase 2 StudyPresenter:Durga Borkar, M.D., MMCiAssociate Professor of OphthalmologyDuke University Eye CenterTime/Date:12:46 p.m. WEST on Saturday, September 14, 2024 Details of the EIS Meeting presentation are as follows: Title:Targeting Fas Pathway: ONL Therapeutics’ Approach to Dry AMD (as part of Session 1: Non-neovascular AMD and IRDs)Presenter:David N. Zacks, M.D., Ph.D.Professor, Ophthalmology and Visual Sciences, University of Michigan Chief Scientific Officer, ONL TherapeuticsTime/Date:1:05 – 1:40 p.m. Central European Summer Time (CEST) on Wednesday, September 18, 2024 About ONL1204 Ophthalmic SolutionONL1204 is a novel, first-in-class small molecule Fas inhibitor designed to protect key retinal cells, including photoreceptors, from cell death that occurs across a range of retinal diseases and conditions. Death of these retinal cells, through both direct and inflammatory signaling pathways, is the root cause of vision loss and the leading cause of blindness. The company’s later-stage clinical development program for ONL1204 includes a Phase 2 study in the U.S. for the treatment of macula-off retinal detachment (NCT05730218), a condition for which the compound has been granted orphan drug designation by the United States Food and Drug Administration (FDA). The company has also conducted a Phase 1b clinical trial in patients with geographic atrophy (GA) associated with age-related macular degeneration (AMD) (NCT04744662) and a Phase 1b clinical trial in patients with progressing open-angle glaucoma (NCT05160805) at sites in Australia and New Zealand. About ONL TherapeuticsONL Therapeutics (ONL) is a clinical-stage biopharmaceutical company committed to developing first-in-class therapeutics to protect and improve the vision of patients with retinal disease. By advancing a breakthrough technology designed to protect key retinal cells from Fas-mediated cell death, ONL is pioneering a new approach to preserving vision. For more information about ONL Therapeutics, please visit www.onltherapeutics.com.

临床1期临床2期孤儿药临床结果

100 项与 Gene Therapy Fas Inhibitor(ONL) 相关的药物交易

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