Limonoid 7-Deacetoxy-7-oxogedunin from Andiroba, Carapa guianensis, Meliaceae, Decreased Body Weight Gain, Improved Insulin Sensitivity, and Activated Brown Adipose Tissue in High-Fat-Diet-Fed Mice

1区 · 农林科学

Article

作者: Tanaka, Reiko ; Maehara, Toko ; Matsumoto, Chihiro ; Fujimori, Ko

We examined the antiobesity effect of a limonoid 7-deacetoxy-7-oxogedunin, named CG-1, purified from the seeds of Carapa guianensis, Meliaceae, known as andiroba in high-fat-diet (HFD)-fed mice. C57BL/6 mice were fed a low-fat diet or an HFD and orally administered CG-1 (20 mg/kg) for 7 weeks. CG-1 lowered the body weight gain and improved the serum triglyceride level and insulin sensitivity in HFD-fed mice. The expression level of the adipogenesis-related genes was lowered by CG-1 in the visceral white adipose tissue (vWAT). The mRNA expression level of the macrophage-related genes decreased in vWAT following the administration of CG-1 to HFD-fed mice. It is noteworthy that CG-1 activated the brown adipose tissue (BAT) with enhanced expression of uncoupling protein 1 and increased the rectal temperature in HFD-fed mice. These results indicate that the limonoid CG-1 decreased body weight gain and ameliorated hypertriglyceridemia and insulin resistance with the activation of BAT in HFD-fed mice.

2018-05-01·Bioorganic & medicinal chemistry letters4区 · 医学

Structural analysis and antioxidant activity of the glycoside from Imperial Chrysanthemum

4区 · 医学

Article

作者: Zhang, Yong-Min ; Pan, Li-Chao ; Zhu, Zhen-Yuan ; Yun-Tang

A new glycoside, named as CG-1, was separated from Imperial Chrysanthemum with silica gel column chromatography. The purity was detected by TLC and HPLC. The crystal shape of CG-1 was consisting of a quadrangular and two rectangular pyramids. The analysis of DSC and TGA showed that the melting point of CG-1 crystal was 150.22 °C and had good thermal stability. The monosaccharide conformation analysis showed that it was d-glucose. The structure characteristics were compared by FT-IR, NMR spectroscopy and LC-MS and a molecular structure has been deduced which consistent with spectroscopic results. In vitro antioxidant results suggested that the glycoside extracted from Imperial Chrysanthemum could be effectively employed as natural antioxidant in health or functional food. This work is of significance to keep the antioxidant activity in the processing and application of Imperial Chrysanthemum.

2016-04-01·European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V2区 · 医学

Co-milling of telmisartan with poly(vinyl alcohol) – An alkalinizer free green approach to ensure its bioavailability

2区 · 医学

Article

作者: Isaac, Jinu ; Ganguly, Swastika ; Ghosh, Animesh

The aim of this study was to enhance the dissolution and bioavailability of telmisartan (TLM), a poorly water soluble drug by co-milling approach. Physical mixtures of TLM and poly(vinyl alcohol) (PVA) were co-milled in a planetary micro mill in a dry condition by varying process parameters such as drug to polymer weight ratio, ball-to-powder weight ratio, and rotational speed. The co-milled products offered cumulative percentage dissolution of TLM above 75% in 30 min (CG 1 and CG2). These samples were characterized using field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Raman spectra analysis. Well-dispersed acicular shaped particles of TLM were observed in co-milled products. A mixture of crystalline and amorphous TLM with a particle size less than 1 μm was present in CG1. The particle size of TLM observed in CG2 was less than 2 μm. In addition to crystalline and amorphous form of TLM, defective/disordered crystals of TLM were also present in CG 2. Therefore, CG2 tablets exhibited poor stability. CG 1 tablets were found to be stable under accelerated stability test conditions. The relative bioavailability of TLM of CG 1 containing tablets in comparison with Micardis® was 93.92±12.84% (in rabbits). Thus, co-milling of TLM with PVA proves to be a promising "alkalinizer free green approach" to ensure the dissolution and bioavailability of poorly water soluble TLM.

项与 CG-01 相关的新闻（医药）

2024-10-28

·Endpoints

Biogen's full Ph2 data for IgA nephropathy drug; Sanofi invests in obesity biotech

Plus, news about Novartis, CombiGene, ProQR and Aardvark Therapeutics: Biogen presents full Phase 2 data for felzartamab: The drug, which was acquired in Biogen’s $1.15 billion buyout of HI-Bio earlier this year, showed patients with IgA nephropathy maintaining a 50% average reduction in a measurement of kidney stabilization after two years. Biogen expects to take the drug into a Phase 3 study but exact details have not yet been disclosed. — Max Gelman Sanofi snags equity in Resalis Therapeutics for undisclosed amount: The new tranche of cash will help the biotech pay for a Phase 2 proof-of-concept study of its lead obesity medicine, called RES-010. Resalis raised €10 million ($10.8 million) in early 2024 to afford the drug’s first obesity trial. — Max Bayer Novartis shares one-year data for Fabhalta in ultra-rare kidney disease: For patients with C3 glomerulopathy, Fabhalta at 12 months sustained reductions in proteinuria that had been seen at six months, when the study reported a 35.1% reduction in protein buildup in the urine compared to placebo. At six months, patients who received placebo in the Phase 3 study were switched over to iptacopan, which Novartis markets as Fabhalta for a rare blood disorder and an autoimmune kidney disease. Novartis submitted the drug for approval in C3G in the EU, China and Japan, and it expects to be in the US by the end of this year. — Lei Lei Wu CombiGene trims pipeline, headcount: The Swedish drugmaker is ending work on its gene therapy candidate for epilepsy, called CG01, and instead prioritizing its chronic pain program, dubbed COZY. CombiGene is also reducing the number of its employees and external consultants by 45% in a bid to extend its cash runway through the second quarter of 2026. It had 11 employees, as of December 2023. — Ayisha Sharma Eli Lilly invests in ProQR as it nabs $75.3M: The company is selling shares for $3.50 apiece, getting $63 million. In addition, the funding includes a private placement from Eli Lilly that totals $12.3 million. — Max Gelman Aardvark Therapeutics buys MEI Pharma’s solid tumor drug: The San Diego-based biotech paid $500,000 upfront for the rights to MEI’s ME-344, an inhibitor of mitochondrial oxidative phosphorylation. MEI is eligible for up to $62 million in milestones. — Ayisha Sharma

临床3期并购上市批准临床2期基因疗法

2021-10-18

·E药经理人

前沿技术新动向 - 武田36亿美元加注基因疗法；通用型CAR-T疗法I期临床试验结果积极

在过去的一周，全球医药前沿技术又有了新动向：武田36亿美元加注基因疗法 CRISPR Therapeutics通用型CAR-T疗法I期临床试验结果积极超9亿美元布局B细胞疗法，Immusoft和武田达成合作 Spark Therapeutics近4亿美元开发治疗癫痫基因疗法 Intellia Therapeutics与SparingVision共同研发新型基因编辑疗法 CureVac放弃第一代新冠mRNA疫苗豪森药业超5亿美元引进siRNA疗法重大事件武田36亿美元加注基因疗法 10月12日，致力于研究下一代细胞与基因疗法的公司Poseida Therapeutics宣布与武田就新型非病毒体内基因疗法达成研究合作和独家许可协议。武田将使用Poseida的piggyBac、Cas-CLOVER、DNA和RNA纳米颗粒递送技术以及其他专有基因工程平台，用于研发多达8种基因疗法。根据协议条款，Poseida将收到4500万美元的预付款和超过1.25亿美元的临床前里程碑付款。如果Poseida实现了6个项目的里程碑事件，将获得最高27亿美元的付款；如果Poseida将8个项目的里程碑事件均实现了，将获得最高36亿美元的付款。细胞与基因疗法 CRISPR Therapeutics通用型CAR-T疗法I期临床试验结果积极 10月12日，专注于研发细胞与基因疗法的公司CRISPR Therapeutics宣布了通用型CAR-T细胞疗法CTX110的I期临床试验最新结果：试验结果积极，安全性与有效性均良好。 CTX110是一款针对CD19+B细胞恶性肿瘤的同种异体CAR-T细胞疗法。在大B细胞淋巴瘤(LBCL)中，单剂量CTX110的剂量水平2(DL2)及以上的意向治疗可实现了58%的总体缓解率(ORR)和38%的完全缓解率(CR)；在LBCL中获得持久反应，6个月CR率为21%，最长反应持续时间在初始输注后超过18个月；没有3级或更高级别的细胞因子释放综合征(CRS)和低感染率和免疫效应细胞相关神经毒性综合征(ICANS)。超9亿美元布局B细胞疗法，Immusoft和武田达成合作 10月13日，致力于改善罕见病患者生活的细胞治疗公司Immusoft宣布与武田签署研究合作和许可选择协议，以发现、开发和商业化治疗罕见病的B细胞疗法。双方将使用Immusoft的免疫系统编程技术平台来研发治疗患者的B细胞疗法。根据协议条款，Immusoft将获得一笔未公开的预付款和研究资金支持。如果在合作过程中行使所有期权并实现所有里程碑，该公司还有资格获得总潜在价值超过9亿美元的未来期权费和里程碑付款。武田可以选择这些临床前的项目并进一步进行临床开发以及商业化。 Spark Therapeutics近4亿美元开发治疗癫痫基因疗法 10月12日，罗氏旗下子公司Spark Therapeutics宣布与专注于研发基因疗法的公司CombiGene AB达成合作。双方针对CombiGene的CG01项目达成独家合作和许可协议。CG01是一款由CombiGene、Cobra Biologics和Viralgen共同开发治疗癫痫的基因治疗候选药物。根据协议，Spark有开发、制造和商业化CG01的独家全球许可。CombiGene将获得850万美元的前期付款和5000万美元的临床前和临床期里程碑付款，其能获得的里程碑付款最高可达3.285亿美元。 Intellia Therapeutics与SparingVision共同研发新型基因编辑疗法 10月13日，基因编辑公司Intellia Therapeutics宣布与开发治疗眼部疾病药物的公司SparingVision达成合作。双方将利用CRISPR/Cas9技术开发治疗眼部疾病的新型基因编辑疗法。根据协议，Intellia将授予SparingVision对CRISPR/Cas9基因编辑技术的独家权利，用于最多三个眼部项目。SparingVision将负责并资助基因编辑产品候选物的临床前和临床开发。Intellia将获得SparingVision 10%的股权，还将有资格获得开发和商业里程碑付款（每个产品大约2亿美元）以及合作产生的产品未来潜在销售的分成。核酸药物 CureVac放弃第一代新冠mRNA疫苗 10月12日，CureVac宣布，将其第一代新冠候选疫苗CVnCoV从欧洲药品管理局(EMA)的当前批准程序中撤回。CureVac表示第一代新冠mRNA疫苗最快在明年第二季才能获得EMA的使用授权，届时与葛兰素史克合作研发的第二代候选疫苗将进入后期临床试验，因此决定撤回申请，将新冠疫苗的开发重点放在与GSK合作上。CureVac表示，期望在2022年上半年将二代新冠疫苗推进到后期临床，并在同一年争取获得监管部门的批准。但CureVac的这一决定也意味着其此前与欧盟委员会此前达成的4.05亿剂疫苗预采购协议也将告终止。豪森药业超5亿美元引进siRNA疗法 10月12日，翰森制药宣布与OliX制药公司达成合作，签署签署许可和合作协议，在中国发现、开发和商业化针对关键靶向适应症的siRNA疗法。根据协议条款，OliX制药公司将利用GalNAc-asiRNA技术平台发现先导药物并保障针对特定靶点的候选药物的开发，涉及领域包括心血管、代谢疾病及其他肝脏相关疾病。翰森制药将拥有这些疗法在中国的独家商业权益，OliX制药将拥有中国以外其他地区的权益，且将收到650万美元的首付款及最高超过4.5亿美元基于重要里程碑的特许权许可分成。

免疫疗法合作基因疗法细胞疗法信使RNA

2021-10-12

·Endpoints

Inhibrx shares rise on PhI trial results; Braglia's Helsinn enters partnership with Fosun

California biotech Inhibrx released interim results today from a Phase I trial looking at a recombinant fusion protein program, INBRX-101. The study looked at patients with alpha-1 antitrypsin deficiency, or AATD. The study revealed interim pharmacokinetic data from 21 patients with AATD, all with the ZZ mutation of the SERPINA1 gene, and interim safety data are from 24 patients with AATD. There were no drug-related severe or serious adverse events at doses up to and including 120 mg/kg single dose, and 80mg/kg multi-dose, according to a company release. Adverse events were predominantly mild with a few moderate events. More results regarding patients’ functional AAT and bronchoalveolar lavage data are expected in the first half of next year, looking at three INBRX-101 doses of 80 or 120 mg/kg IV administered every three weeks. Share prices $INBX went on a high after the announcement, increasing over 25% before the market open and hovering up 20% to 25% after the opening bell. “These initial data demonstrate the potential of INBRX-101 to significantly improve treatment for patients with AATD by maintaining them in the normal range of functional AAT and reducing infusions from 52 annually to possibly as few as 12 annually,” said Inhibrx CEO Mark Lappe. Swiss biotech Helsinn announced today a new licensing and distribution partnership with Shanghai-based Fosun, effective October 1 . This partnership with Fosun grants the Chinese biotech license to commercialize and sell three Helsinn drugs in China, Hong Kong and Macau — anti-nausea and anti-vomiting drugs Aloxi and Akynzeo, along with anorexia and malignancy-associated weight loss treatment anamorelin for patients with NSCLC. Additionally, Helsinn’s Chinese subsidiary will provide a Fosun subsidiary with certain medical, marketing and commercial services, including co-promotion services in Shanghai. Wu Yifang, Chairman and CEO of Fosun Pharma, commented: “We are looking forward to working with Helsinn and to making these therapies available to patients in these territories as soon as possible.” In another Asia-focused collaboration, China’s Hansoh Pharma and South Korea RNA biotech OliX Pharmaceuticals are teaming up in a new licensing and collaboration agreement. The deal will be to discover, develop and commercialize siRNA therapeutics for certain indications in China, Taiwan, Hong Kong and Macau, according to a company statement . While OliX will use its platform to discover and develop candidates for targets in cardiovascular, metabolic, and other diseases associated with the liver, Hansoh will have exclusive commercial rights to these candidates in the four Asian markets. OliX will receive an initial upfront payment of $6.5 million, with up to $450 million in milestones plus royalties, along with rights to the therapeutic candidates in the rest of the world. “We are thrilled to partner with OliX Pharmaceuticals, a leader in siRNA development with an established clinical stage portfolio, and look forward to utilizing their technology platform in our development process,” said Hansoh board executive director Eliza Sun. In yet another collaboration announced today , CombiGene and Spark signed an agreement to exclusively collaborate on the former’s focal epilepsy gene therapy — with a $300M+ licensing deal to boot. The agreement gives Roche-owned Spark the worldwide license to develop, manufacture and commercialize CG01 while CombiGene continues parts of the preclinical program in tandem with the company. CombiGene will get $8.5 million upfront from Spark as part of the arrangement — with an additional $50 million in milestones and a potential grand total of $328.5 million. And that does not include royalties, either. Once the gene therapy is commercialized, CombiGene is eligible for tiered royalties based on net sales. “We look forward to advancing this potentially transformative therapy together with Spark for the benefit of a patient group in need of better treatments,” said CombiGene CEO Jan Nilsson.

合作基因疗法财报引进/卖出siRNA

100 项与 CG-01 相关的药物交易

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