Six undescribed bicyclic sesquiterpene coumarins, kuhistanin A, ferukrin isovalerate, 9'β,12'α - ferukrin isovalerate, (17'E)- 9'α, 12'β - isomarcandin, (17'Z)- 9'α, 12'β - isomarcandin and (17'E) - isomarcandin, together with nine known ones were isolated from the roots of Ferula kuhistanica Korovin. The structures of them were elucidated using NMR and HRESIMS data analysis. The relative configurations of the isolates were confirmed by NOE correlations and NMR calculation. The absolute configurations of them were confirmed by X-ray diffraction analysis and ECD calculation. Anti-vitiligo, anti-inflammatory and cytotoxicity of the isolates were tested. Acetyl feselol, feselol, ferusingensine I and farnesiferol A significantly increased the melanin content at the concentration of 10 μM. (17'E) - 9'α, 12'β - isomarcandin exhibited strong cytotoxicity against HT-29 cell line with IC₅₀ values of 8.94 ± 0.47 μM, and (17'E) - isomarcandin demonstrated strong cytotoxicity against Hela, A549 and HT-29 cell lines with IC₅₀ values of 5.29 ± 0.25, 4.01 ± 0.20, and 4.16 ± 0.21 μM, respectively. This study concluded that, isolated compounds from F. kuhistanica demonstrated strong bioactivity towards anti-vitiligo and cytotoxicity and active compounds are suggested as anti-vitiligo and cytotoxicity agent for future drug development.

2023-03-01·Acta Crystallographica Section E Crystallographic Communications

Crystal structures of two 1,2,3,4-tetrahydronaphthalenes obtained during efforts towards the total synthesis of elisabethin A

Article

作者: Enev, Valentin ; Weil, Matthias ; Kaiser, Maximilian ; Gärtner, Peter

The two substituted 1,2,3,4-tetrahydronaphthalenes, methyl (R)-3-{(1R,4S)-6-methoxy-4,7-dimethyl-5,8-bis[(triisopropylsilyl)oxy]-1,2,3,4-tetrahydronaphthalen-1-yl}butanoate, C36H66O5Si2, (2), and methyl (E)-3-{(1R,4S)-8-hydroxy-6-methoxy-4,7-dimethyl-5-[(triisopropylsilyl)oxy]-1,2,3,4-tetrahydronaphthalen-1-yl}acrylate, C26H42O5Si, (8), crystallize in the Sohncke space groups P212121 and P21, respectively, with the absolute structure determined on the basis of anomalous dispersion effects. The configurations of the stereo centres in the 1,2,3,4-tetrahydronaphthalene moiety of (2) and (8) are the same, and the conformation of the non-aromatic part of the ring system is nearly identical. In the crystal of (2), weak non-classical C—H...O interactions consolidate the packing, whereas in (8), intermolecular O—H...O hydrogen-bonding interactions of medium-to-weak strength direct the molecules into Z-shaped strands extending parallel to [010].

2022-06-28·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Tas2R activation relaxes airway smooth muscle by release of Gα _t targeting on AChR signaling

1区 · 综合性期刊

Article

作者: Sun, Jie ; Jiang, Zhi-Hui ; Ma, Ming ; Tao, Tao ; Wang, Ye ; Wang, Han ; Yang, Li-Yuan ; Chen, Cai-Ping ; Zhang, Zhong-Liang ; Zhang, Jian ; Li, Ye-Qiong ; Zhu, Min-Sheng ; Wang, Pei ; Chen, Xin ; Zhang, Xue-Na ; Chen, Hua-Qun ; Pan, Yang ; Zhou, Yu-Wei ; Qiu, Tian-Tian

Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor–mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gα t proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gα t released by Tas2R activation complexes with AChR and blocks the Gα q cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gα q -associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD.

项与苦丁皂苷A 相关的新闻（医药）

2024-01-26

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【瞩目】正大天晴1类新药来袭，瞄准210亿市场

精彩内容1月26日，CDE官网显示，正大天晴的1类新药TQC3927吸入粉雾剂临床试验申请获得承办。米内网数据显示，2022年中国公立医疗机构终端吸入剂销售额超过210亿元。1类新药TQC3927吸入粉雾剂属于吸入制剂创新药。吸入制剂是指利用吸入装置将药物递送进入呼吸道发挥局部或全身治疗作用的制剂，具有起效快、药量小、药品不良反应少、使用方便等特点。米内网数据显示，2022年中国城市公立医院、县级公立医院、城市社区中心及乡镇卫生院（简称中国公立医疗机构）终端吸入剂销售额超过210亿元；2023年上半年其销售额超过120亿元，同比增长9.85%。中国公立医疗机构终端吸入剂销售情况（单位：万元）来源：米内网中国公立医疗机构药品终端竞争格局TQC3927吸入粉雾剂是正大天晴第2款吸入制剂创新药，公司首款吸入制剂创新药——吸入用TQC3721混悬液已处于Ⅱ期临床阶段，用于中重度慢性阻塞性肺病。在吸入制剂仿制药方面，正大天晴已有4款产品富马酸福莫特罗粉吸入剂、噻托溴铵粉雾剂、吸入用布地奈德混悬液、吸入用氯醋甲胆碱获批上市，且均为国内首仿。正大天晴获批吸入制剂来源：米内网中国上市药品（MID）数据库国内布局吸入制剂创新药的企业并不多见，但呈上升趋势。2021年国内仅有正大天晴的吸入用TQC3721混悬液、上海凯屹医药的吸入用苦丁皂苷A溶液获批临床；2022年有安徽柏拉阿图的PA9159吸入气雾剂、恒瑞医药的HRS-9821吸入混悬液、鲁抗医药的TRN-157雾化吸入剂获批临床。2023年国内有5款吸入制剂创新药获批临床，包括循曜生物的重组抗PEAR1单克隆抗体雾化吸入溶液、惠泰生物的吸入用HTPEP-001、上洛启生物的LQ036单域抗体吸入用粉末、吉锐生物的GB002重组多肽吸入溶液、硕佰医药的DBM-1152A吸入溶液。值得一提的是，2024年伊始，正大天晴已有2款1类新药TQB3006片、TQC3927吸入粉雾剂申报IND，7款1类新药获得临床试验默示许可，公司创新研发的步伐持续加快。资料来源：米内网数据库、CDE注：米内网《中国公立医疗机构药品终端竞争格局》，统计范围是：中国城市公立医院、县级公立医院、城市社区中心以及乡镇卫生院，不含民营医院、私人诊所、村卫生室；上述销售额以产品在终端的平均零售价计算。本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092●温馨提示●因为微信公众号修改了推送规则，最近很多读者反映没有及时看到推文。把米内网设为“星标”，就能每天与我们不见不散啦，具体操作如下：【分享、点赞、在看】点一点不失联哦

临床申请抗体药物偶联物信使RNA

100 项与苦丁皂苷A 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
哮喘	临床2期	中国	上海凯屹医药科技有限公司	2024-04-16
慢性阻塞性肺疾病	临床1期	中国	上海凯屹医药科技有限公司	2022-12-14
支气管扩张	临床1期	中国	浙江我武生物科技股份有限公司	2022-01-30

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


CTR20211313 (NEWS) 人工标引	临床1期	慢性阻塞性肺疾病 \| 哮喘	-	Kubutin A	(選窪選觸範願顧糧膚觸) = 網襯願構遞夢廠繭鏇鑰鏇夢觸淵繭築餘簾鏇鬱 (壓膚範鹹蓋糧憲夢艱壓 ) 更多	积极	2022-08-19