A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of a 12-week Administration of OATD-01, an Oral Inhibitor of Chitinase-1 (CHIT1), for the Treatment of Active Pulmonary Sarcoidosis (the KITE Study)

This is a Phase 2, randomized, double-blind, placebo-controlled, adaptive, multicenter study to evaluate the efficacy, safety, tolerability, Pharmacodynamics (PD), and Pharmacokinetics (PK) of OATD-01 in the treatment of subjects with active pulmonary sarcoidosis.

开始日期2024-03-21

申办/合作机构

Molecure SA

NCT05030857 / Completed临床1期

An Open-label, Fixed Sequence, Drug-drug Interaction Study in Healthy Subjects to Evaluate the Effect of GLPG4716 on the Pharmacokinetics of Midazolam, a Sensitive Index Substrate of CYP3A4, and to Assess the Effect of Food on the Pharmacokinetics of GLPG4716

The purpose of this study is to determine the effect of the administration of multiple doses of GLPG4716 on the amount of midazolam (MDZ) that gets into the blood when the two drugs are administered together compared to when midazolam is administered alone. Other objectives of this study are to evaluate the safety and tolerability of GLPG4716 when administered with midazolam and assess the amount of GLPG4716 that gets into the blood when administered with midazolam. This study will also assess the effect of food on the amount of GLPG4716 that gets into the blood.

开始日期2021-09-08

申办/合作机构

Galapagos NV

100 项与 Chitinases x AMCase 相关的临床结果

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100 项与 Chitinases x AMCase 相关的转化医学

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0 项与 Chitinases x AMCase 相关的专利（医药）

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项与 Chitinases x AMCase 相关的文献（医药）

2024-12-31·Gut Microbes

ChiA: a major player in the virulence of Crohn’s disease-associated adherent and invasive Escherichia coli (AIEC)

Article

作者: Denizot, Jérémy ; Rodrigues, Michael ; Faure, Frederic ; Fargeas, Margot ; Barnich, Nicolas ; Billard, Elisabeth ; Chevarin, Caroline ; Douadi, Clara ; Birer, Aurélien ; Buisson, Anthony ; Sivignon, Adeline

We investigated the role of ChiA and its associated polymorphisms in the interaction between Crohn's disease (CD)-associated adherent-invasive Escherichia coli (AIEC) and intestinal mucosa. We observed a higher abundance of chiA among the metagenome of CD patients compared to healthy subjects. In dextran sulfate sodium-induced colitis mice model, AIEC-LF82∆chiA colonization was reduced in ileal, colonic and fecal samples compared to wild-type LF82. The binding of ChiA to recombinant human CHI3L1 or mucus was higher with the pathogenic polymorphism. The strength of ChiA-mucin interaction was 300-fold stronger than ChiA-rhCHI3L1. ChiA was able to degrade mucin to promote its growth and enabled LF82 to get closer to epithelial cells. The pathogenic polymorphism of ChiA had a stronger impact on mucus degradation than on the binding capability of AIEC to adhere to the intestinal epithelium. We observed that ChiA could favor an efficient bacterial invasion of intestinal crypts, and that ChiA, especially its pathogenic polymorphism, gives LF82 an advantage to uptake within Peyer's patches, macrophages and mesenteric lymph nodes. All together, these data support the role of ChiA in the virulence of AIEC and show that it could be a promising target to reduce AIEC colonization in patients with CD.

2024-12-01·Journal of Hazardous Materials

PBAT biodegradable microplastics enhanced organic matter decomposition capacity and CO2 emission in soils with and without straw residue

Article

作者: He, Huan ; Li, Shiyin ; Zhou, Aoyu ; Zhu, Fengxiao ; Chen, Chao ; Fu, Qing-Long ; Chang, Sha ; Hua, Zhuyao

Recent studies show that biodegradable microplastics (BMPs) could increase soil CO₂ emission, but whether altered carbon emission results from modified soil organic matter (SOM) decomposition remains underexplored. In this study, the effect and mechanisms of BMPs on CO₂ emission from soil were investigated, using poly(butylene adipate-co-terephthalate) (PBAT, the main component of agricultural film) as an example. Considering that straw returning is a common agronomic measure which may interact with microplastics through affecting microbial activity, both soils with and without wheat straw were included. After 120 d, 1 % (w/w) PBAT BMPs ificantly increased cumulative CO₂ emission by 1605.6 and 1827.7 mg C kg^-1 in soils without and with straw, respectively. Cracks occurred on the surface of microplastics, indicating that CO₂ was partly originated from plastic degradation. Soil dissolved organic matter (DOM) content, carbon degradation gene abundance (such as abfA, xylA and manB for hemicellulose, mnp, glx and lig for lignin, and chiA for chitin) and enzyme activities increased, which significantly positively correlated with CO₂ emission rate (p < 0.05), suggesting that PBAT enhanced carbon emission by stimulating the decomposition of SOM (and possibly the newly added straw) via co-metabolism and nitrogen mining. This is supported by DOM molecular composition analysis which also demonstrated stimulated turnover of carbohydrates, amino sugars and lignin following PBAT addition. The findings highlight the potential of BMPs to affect SOM stability and carbon emission.

2024-11-01·Protein Expression and Purification

Identification of chitinase from Bacillus velezensis strain S161 and its antifungal activity against Penicillium digitatum

Article

作者: Liu, Feng ; Chen, Song ; Chen, Xingbang ; Yong, Bin ; He, Bing

Previous studies have demonstrated the presence of chitinase in Bacillus velezensis through extensive genomic sequencing and experimental analyses. However, the detailed structure, functional roles, and antifungal activity of these chitinases remain poorly characterized. In this study, genomic screening identified three genes-chiA, chiB, and lpmo10-associated with chitinase degradation in B. velezensis S161. These genes encode chitinases ChiA and ChiB, and lytic polysaccharide monooxygenase LPMO10. Both ChiA and ChiB contain two CBM50 binding domains and one catalytic domain, whereas LPMO10 includes a signal peptide and a single catalytic domain. The chitinases ChiA, its truncated variant ChiA2, and ChiB were heterologously expressed in Escherichia coli. The purified enzymes efficiently degraded colloidal chitin and inhibited the spore germination of Penicillium digitatum. Notably, even after losing one CBM50 domain, the resultant enzyme, consisting of the remaining CBM50 domain and the catalytic domain, maintained its colloidal chitin hydrolysis and antifungal activity, indicating commendable stability. These results underscore the role of B. velezensis chitinases in suppressing plant pathogenic fungi and provide a solid foundation for developing and applying chitinase-based biocontrol strategies.

项与 Chitinases x AMCase 相关的新闻（医药）

2022-06-24

·PRNewswire

Molecure to regain worldwide rights to dual chitinase inhibitor OATD-01

WARSAW, June 23, 2022 /PRNewswire/ -- Molecure S.A. ("Molecure": WSE: MOC) a clinical stage biotechnology company that uses its world leading medicinal capabilities to discover and develop first in class small molecule drug candidates that directly modulate RNA and unexplored protein targets to treat multiple incurable diseases, announces today that it has regained full rights to its dual chitinase inhibitor OATD-01 together with all the related IP and know-how, full drug substance and drug product inventory. This is the result of an ongoing corporate strategy and portfolio review by its partner Galapagos NV. Marcin Szumowski, Molecure CEO commented "We have enjoyed a very productive relationship with Galapagos and are pleased that we have been able to regain rights to OATD-01, which we believe holds great promise in several respiratory indications. Data generated to date reveal an attractive benefit-risk profile for this asset, and we look forward to revising our clinical strategy for the further development and subsequent partnering of this program in the near future." Andre Hoekema, Ph.D., Chief Business Officer of Galapagos added "We are grateful to have had the opportunity to partner with Molecure and to work on OATD-01. However, as part of an ongoing strategic exercise to renew and accelerate our portfolio, we decided to return all rights to OATD-01 to Molecure, with the confidence that they will progress this promising asset through the next stages of development." The return of OATD-01 and associated chitinase inhibitor programs provides Molecure with a renewed opportunity to generate value for its shareholders. Once the internal assessment of data, reports and information received from Galapagos is completed, Molecure considers to initially develop OATD-01 in sarcoidosis, its preferred and originally selected indication. The company will seek the optimum path forward in this indication, with the intention to conduct a Phase II proof-of-concept (PoC) study. This will likely be an international study recruiting patients in the United States and Europe, including Poland. Molecure has regained (at no cost) the full and exclusive rights to the results of all research, pre-clinical and clinical development performed by Galapagos with OATD-01 over the course of the last 18 months. The non-refundable Eur27 million received by Molecure in November 2020 as part of the original licensing deal and right of first negotiation of other molecules from its chitinase platform could support this important Phase II clinical study. Molecure believes that the studies performed by Galapagos together with the scientific advice received from the EMA are highly supportive of further progressing OATD-01 into phase II clinical trials in the near term. Molecure is confident that a positive result from the planned Phase II PoC study in sarcoidosis patients would open the possibility for the company to partner OATD-01 and its chitinase inhibitor IP for the second time. Molecure is committed to solving unmet medical needs of patients with interstitial lung diseases, inflammation driven fibrosis and cancer. The Company looks forward to further informing investors on the next steps in the planned clinical development for OATD-01 in the coming weeks. Dr Samson Fung, Molecure CMO, commented "Sarcoidosis is a systemic disease of unknown cause that is characterized by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Sarcoidosis is a global disease, affecting both men and women with a prevalence of about 5–50 in 100 000, with 70% of the patients aged between 25 and 45 years. The most severe and frequent complication of sarcoidosis is the occurrence of pulmonary fibrosis. This is usually associated with significant impairment of pulmonary function. Pulmonary fibrosis results in the majority of deaths related to sarcoidosis in western countries. There is currently no cure for sarcoidosis and treatments only modify the granulomatous process and its clinical consequences. During preclinical development, OATD-01 has been shown to significantly decrease the disease burden in the lungs of treated animals. In patients, the over-expression of CHIT1, the target of OATD-01 is both a marker of severity and disease progression."

限制授权使用First in Class小分子药物