This study will test the hypothesis that a novel combination of three drugs (sorafenib, sonidegib, and irinotecan), in conjunction with individually optimized doses, can be safely administered and lead to improved clinical outcomes in patients with hepatocellular carcinoma compared to standard of care. The main objective of this study is to establish safe dose ranges for the coadministration of sorafenib, sonidegib, and irinotecan in patients with hepatocellular carcinoma. Furthermore, we will collect data to inform the application of an artificial intelligence/computational approach to individual dosing of combination chemotherapy. Individualization of dosing will be achieved by using Phenotypic Personalized Medicine (PPM) to maximize treatment efficacy in patients with hepatocellular carcinoma, while minimizing toxicity. Drug efficacy will be assessed by measuring plasma circulating tumor DNA (ctDNA). Toxicity will be assessed by quantitating organ injury and patient tolerability. Recommended dosing for future studies will be based on the totality of the data.

开始日期2024-12-02

申办/合作机构

University of Florida

[+1]

ChiCTR2400081793 / RecruitingN/AIIT

Sonidegib for Acute ischemic patients with large VEssel occlusion combined with Revascularization (SAVER), a multi-center, prospective, randomized trial

开始日期2024-03-12

申办/合作机构

中国人民解放军第二军医大学

ACTRN12623001216606 / Recruiting临床2期IIT

Single-institution, single-arm, open-label phase II basket study investigating the effect of mutation and/or elevated hedgehog (Hh) expression-directed smoothened inhibitor sonidegib in patients with advanced solid malignancies

开始日期2023-12-12

申办/合作机构

Northern Sydney Local Health District

100 项与磷酸索立德吉相关的临床结果

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100 项与磷酸索立德吉相关的转化医学

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100 项与磷酸索立德吉相关的专利（医药）

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项与磷酸索立德吉相关的文献（医药）

2025-02-01·TISSUE & CELL

The Shh-p38-NFATc1 signaling pathway is essential for osteoclastogenesis during tooth eruption

Article

作者: Huang, Xiaofeng ; Wang, Jiran ; Liu, Jinan ; Jia, Xueting ; Huang, Rui

Tooth eruption, a critical stage in tooth development, is related to osteoclastogenesis. Intraperitoneal injection of Shh agonists into neonatal mice promoted tooth eruption at postnatal day (PN) 15, whereas treatment with the Shh inhibitor (LDE225) suppressed this process. When RAW264.7 osteoclast precursor cells were treated with RANKL, NFATc1 translocated from the cytoplasm to the nucleus and induced cell differentiation into TRAP⁺ osteoclasts; this process was activated by Shh but inhibited by LDE225. Treating RAW264.7 cells with the p38 inhibitor, BIRB796, also inhibited NFATc1 nuclear localization. p-p38 expression in the alveolar bone of PN3 and PN5 mice was decreased by treatment with LDE225, and RAW264.7 cell differentiation was reduced by BIRB796, regardless of treatment with Shh. Furthermore, Shh activated p38 signaling pathway in RAW264.7 cells, while p38 phosphorylation was reduced by LDE225, which ultimately inhibited osteoclast precursor differentiation. Therefore, we concluded that Shh promotes osteoclast precursor differentiation via the p38-NFATc1 signaling pathway.

2024-12-18·Journal of the American Chemical Society

Catalytic Intermolecular Asymmetric [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes: Practical Synthesis of Enantioenriched Highly Substituted Bicyclo[2.1.1]hexanes

Article

作者: Fan, Tingting ; Wu, Lihong ; Liu, Xin-Yuan ; Gu, Qiang-Shuai ; Fu, Fang-Lei ; Peng, Ai-Ting ; Lin, Jin-Shun ; Wu, Zhi-Long ; Wang, Yu-Tao ; Li, Ying-Jie ; Wu, Ji-Peng ; Sang, Fan ; Jiang, Yuyang ; Duan, Ming-Hao

The high percentage of sp³-hybridized carbons and the presence of chiral carbon centers could contribute to increased molecular complexity, enhancing the likelihood of clinical success of drug candidates. Three-dimensional (3D) bridged motifs have recently garnered significant interest in medicinal chemistry. Bicyclo[2.1.1]hexanes (BCHs) are emerging 3D benzene bioisosteres, but the synthesis of chiral, highly substituted BCHs has been underexplored. Herein, we disclose the Lewis acid-catalyzed asymmetric intermolecular [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes with coumarins, 2-pyrone, or chromenes to access diverse enantioenriched 1,2,3,4-tetrasubstituted BCHs bearing vicinal tertiary-quaternary stereocenters. The key to success is the introduction of chiral bisoxazoline ligands to effectively suppress the side reactions, inhibit significant racemic background reactions, and fine-tune the reactivity and regio-, enantio-, and diastereoselectivities of the reactions. The resulting BCHs hold significant potential as benzene bioisosteres in the synthesis of chiral BCHex-Sonidegib and BCHex-BMS-202, mimicking the anticancer drug Sonidegib and the PD-1/PD-L1 inhibitor BMS-202, respectively. The outcome highlights the positive impact of bioisosteric replacement on physicochemical properties, while maintaining comparable antitumor activity to their aryl-containing counterparts.

2024-12-01·AUSTRALASIAN JOURNAL OF DERMATOLOGY

Real‐world data on the efficacy and safety of hedgehog pathway inhibitors in patients with basal cell carcinoma: Experience of a tertiary Australian centre

Article

作者: Liu, R. ; Peera, M. ; Truong, K. ; Wijaya, M. ; Fernandez‐Penas, P. ; Jones‐Caballero, M. ; Araujo, R. Ruiz

Abstract:

Background:

Basal cell carcinomas (BCCs) are the most common cancers worldwide. Although most BCCs are amenable to local treatment, there are limited therapeutic options for surgically unresectable locally advanced and metastatic BCCs. Activation of the sonic hedgehog signalling pathway plays a significant role in the development of most BCCs. Hedgehog pathway inhibitors (HPIs) can be used to inhibit this pathway. Efficacy and safety data on HPI use in Australia is scarce.

Objectives:

This study aims to present the effectiveness and safety of HPI at a tertiary dermatology referral centre.

Methods:

We conducted a retrospective analysis of the clinical charts of all patients with BCC treated with an HPI at a tertiary Dermatology referral centre in New South Wales, Australia from 1 January 2016 to 1 July 2023.

Results:

Twenty‐three patients with BCCs were treated with an HPI; 11 locally advanced, 8 multiple, 3 basal cell naevus syndrome and 1 metastatic. All patients were of Caucasian background, with a median age of 56. Across 41 treatment cycles, the median treatment duration was 4 months. The overall response rate (ORR) was 20/23 (87%) and complete response (CR) rate was 9/23 (39%); patients treated with sonidegib achieved an ORR of 11/12 (92%) and CR of 4/12 (33%), and vismodegib‐treated patients achieved an ORR of 9/11 (82%) and CR of 5/11 (45%). Patients who responded to HPI treatment also responded to a subsequent HPI rechallenge. Common treatment emergent adverse events (TEAEs) included muscle spasms, dysgeusia and alopecia. Dysgeusia was more frequent with vismodegib than sonidegib (p = 0.0001). There was no evidence to suggest a difference in other TEAEs between the two HPIs. Four treatment cycles were stopped due to grade 3 muscle spasm.

Conclusions:

In our cohort of 23 patients being treated with HPI, the ORR was 87% and CR was 39%. All patients who experienced TEAEs and had a drug holiday successfully responded to HPI rechallenge. TEAEs, particularly muscle spasms, are common reasons for treatment cessation. Clinicians should implement strategies to mitigate TEAE to improve drug survivability.

项与磷酸索立德吉相关的新闻（医药）

2024-12-11

·Business Wire

Genesis Therapeutics Expands Leadership Team with Appointments of Chief Scientific Officer, SVP of Engineering, and Board Chairman

BURLINGAME, Calif.--( BUSINESS WIRE )-- Genesis Therapeutics , a company pioneering artificial intelligence (AI) technologies to create breakthrough medicines for patients, today announced the appointments of three key members during 2024 to its senior leadership team and Board of Directors: Shifeng Pan, Ph.D., as Chief Scientific Officer; Alla Ivanova as Senior Vice President of Engineering; and Paul A. Friedman, M.D., as Chairman of the Board. “ We are thrilled to welcome to our team these exceptional leaders who share belief in our mission and approach to transforming drug discovery with groundbreaking predictive and generative AI technologies,” said Evan Feinberg, Ph.D., founder and CEO of Genesis. “ Their industrial expertise across technology and drug discovery will enable us to further advance our GEMS (Genesis Exploration of Molecular Space) AI platform, expand our therapeutic pipeline, and ultimately create breakthrough treatments for patients suffering from severe diseases.” Shifeng Pan, Ph.D., Chief Scientific Officer: Dr. Pan joined Genesis in April 2024 and oversees R&D activities for Genesis’ pipeline of AI-enabled therapeutics. He brings more than two decades of experience in medicinal chemistry and biopharmaceutical research, including a 22-year career at Novartis, where he served as Head of Discovery Chemistry at the Genomics Institute of the Novartis Research Foundation. At Novartis, he led the discovery of FDA-approved drugs ODOMZO ® , BRAFTOVI ® , and MAYZENT ® , as well as numerous other programs across several therapeutic areas. Dr. Pan joins Genesis from Odyssey Therapeutics, where he was Executive Vice President and Head of Discovery. He earned a doctorate in organic chemistry from New York University. “ Genesis’ AI capabilities enable the discovery of novel and breakthrough molecules, making its platform well-suited to address challenging or historically undruggable targets,” said Dr. Pan. “ It’s an exciting time for the field of AI-enabled drug discovery and our premier team of engineers, chemists, and biologists who are leveraging the GEMS platform to rapidly advance our broad therapeutic pipeline.” Alla Ivanova, Senior Vice President of Engineering: Ms. Ivanova joined Genesis in November 2024 and brings over 25 years of experience driving innovation in software development; spanning data center management, large-scale infrastructure, and high-traffic web applications to cutting-edge AI/ML solutions. She has held executive leadership roles at notable tech companies including Head of Looker Engineering at Google Cloud, VP of Cloud & Data Infrastructure at Atlassian, Head of Core Infrastructure at Uber, Senior Director of Data Platform at Groupon, and Software Engineering Manager at Netflix. Ms. Ivanova earned her master's degree in applied mathematics and computer science from Kazan Federal University. “ At a time when AI is redefining the boundaries of what’s possible in drug discovery, I’m honored to be joining the Genesis team,” said Ms. Ivanova. “ The company’s AI platform, GEMS, has the potential to unlock the promise of computational drug design and discover life-changing medicines for patients. I’m excited to continue advancing transformational AI work, not just for innovation’s sake but to make a meaningful difference in human health – a mission that resonates deeply with me and the future I envision for AI.” Paul A. Friedman, M.D., Chairman of the Board of Directors: Dr. Friedman has served as Chairman of the company’s Board of Directors since April 2024. With decades of experience in biotechnology and drug development, he has held senior leadership roles at notable pharmaceutical companies, including CEO of Madrigal Pharmaceuticals (2016–2023), CEO of Incyte (2001–2014), President of Research and Development at DuPont-Merck Pharmaceutical, President of DuPont Pharmaceuticals Research Laboratories, and Senior Vice President of Merck Research Laboratories. He has also served as a board member for several publicly held pharmaceutical companies, including Incyte and Alexion. A diplomate of the American Board of Internal Medicine and member of the American Society of Clinical Investigation, Dr. Friedman earned his medical degree from Harvard Medical School. " Genesis is in an exciting period of growth following an outstanding Series B fundraise last year and recent collaboration with Gilead, positioning the company well to advance and expand its AI-enabled pipeline to develop breakthrough therapies for patients,” said Dr. Friedman. This expansion of Genesis’ senior leadership team follows the company’s appointments of two industry veterans to its Board of Directors: Vijay Pande, Ph.D., Founding General Partner at Andreessen Horowitz’s (a16z) Bio + Health fund, joined as a Director in 2023, and Mohamed “Sid” Siddeek, Vice President and Head of NVentures, NVIDIA’s venture capital arm, joined as an observer in 2024. About Genesis Therapeutics Genesis Therapeutics is pioneering AI for biotechnology by leveraging its generative and predictive AI platform called GEMS (Genesis Exploration of Molecular Space) for small molecule drug discovery. GEMS synthesizes proprietary AI methods, including language models, diffusion models, and physical ML simulations, to generate and optimize molecules for complex targets. Genesis has raised over $300 million from leading life science, tech, and AI-focused investors, and is building a therapeutic pipeline for a variety of high-impact targets. Genesis is headquartered in Burlingame, CA, with a fully integrated laboratory in San Diego. For more information on Genesis, please visit the company’s website at www.genesistherapeutics.ai .

高管变更

2024-10-25

·PRNewswire

Sun Pharma Announces Multiple Data Presentations Highlighting its Dermatology Portfolio to be Featured at the 2024 Fall Clinical Dermatology Conference

Data from a wide range of the Sun Pharma dermatology portfolio, including data on alopecia areata, psoriasis, acne and actinic keratosis products, will be highlighted during the meeting. MUMBAI, India and PRINCETON, N.J., Oct. 25, 2024 /PRNewswire/ -- Sun Pharmaceutical Industries Limited (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715 (together with its subsidiaries and/or affiliated companies, "Sun Pharma") today announced it will present more than a dozen posters at the 44th Annual Fall Clinical Dermatology Conference, being held October 24-27, 2024, in Las Vegas, Nevada. The presentations will include data from across the Sun Pharma dermatology portfolio, including study results for LEQSELVI™ (deuruxolitinib), WINLEVI® (clascoterone), ILUMYA® (tildrakizumab-asmn), ODOMZO® (sonidegib) and LEVULAN® KERASTICK® (aminolevulinic acid HCl) + BLU-U® (blue light photodynamic therapy). "As an organization dedicated to supporting the dermatology community, the Fall Clinical Dermatology Conference offers a vitally important forum to present new data and highlight how Sun's innovative dermatology portfolio can support those living with alopecia areata, psoriasis, acne and other skin-related diseases," said Marek Honczarenko, MD, PhD, Senior Vice President and Head of Global Development at Sun Pharma. "We look forward to sharing data from across our portfolio with the dermatology research community and our esteemed industry colleagues." Six abstracts, accepted for poster presentations, will highlight clinical efficacy and safety data of LEQSELVI™ (deuruxolitinib). Approved earlier this year by the U.S. Food and Drug Administration for the treatment of adults with severe alopecia areata, LEQSELVI™ is an oral JAK inhibitor that interrupts the pathways thought to contribute to hair loss in severe AA and delivered statistically significant efficacy at 24 weeks across two Phase 3 clinical trials. LEQSELVI™ data being presented at Fall Clinical showcase pooled long-term results for ongoing clinically meaningful improvements in scalp hair regrowth in adults with alopecia areata. Additionally, two posters will present patient and clinician preferences for the treatment of alopecia areata. The WINLEVI® poster presentations will include new data showing significant reductions in casual facial sebum levels from baseline, stability in the presence of other commonly prescribed acne medications, and efficacy and safety from a pilot study in patients with skin of color. The conference will also feature data from three additional WINLEVI® studies. Sun Pharma will present the following posters at the 2024 Fall Clinical Dermatology Conference: LEQSELVI™ Presentations: Deuruxolitinib results in ongoing clinically meaningful improvements in scalp hair regrowth in adults with alopecia areata: Pooled long-term efficacy and safety data from the open-label extension studies Patient Preferences for the Treatment of Alopecia Areata A Discrete Choice Experiment to Assess Clinician Preferences for the Treatment of Alopecia Optimization of deuruxolitinib dosing in adult patients with alopecia area: Results from a randomized, parallel-group, multicenter Phase 2 trial Change in patient-reported hair satisfaction during deuruxolitinib treatment of severe alopecia areata: Pooled data from the Phase 3 THRIVE-AA1 and THRIVE-AA2 trials Improvement in anxiety and depression in adult patients with severe alopecia areata treated with deuruxolitinib: Pooled data from the THRIVE-AA1 and THRIVE-AA2 Phase 3 trials WINLEVI® Presentations: Clinical evaluation of the sebum reduction induced by clascoterone cream 1%: Week 12 interim analysis Assessment of clascoterone cream 1% levels when layered with other topical acne medications Efficacy and safety of clascoterone cream 1% in patients with acne with skin of color: 16-week interim analysis The efficacy and safety of clascoterone cream 1% for the treatment of acne vulgaris are not dependent on patient age and sex: Results of a post hoc analysis Improvement in skin moisturization and lack of barrier damage with clascoterone cream 1% treatment: Results of a randomized, single-blind, split-face study in acne-prone individuals Comparison of the efficacy of clascoterone vs trifarotene and tazarotene for the treatment of acne vulgaris at Week 12: A systematic review and meta-analysis ILUMYA® Presentation: A systematic literature review and meta-analysis of the real-world effectiveness, quality of life, and safety of tildrakizumab for moderate-to-severe plaque psoriasis ODOMZO® Presentation: Lower rate of discontinuation of sonidegib compared to vismodegib in a real-world analysis of patients with basal cell carcinoma LEVULAN® KERASTICK® + BLU-U® Presentation: Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ About Sun Pharmaceutical Industries Limited. (CIN – L24230GJ1993PLC019050) Sun Pharma is the world's leading specialty generics company with a presence in Specialty, Generics and Consumer Healthcare products. It is the largest pharmaceutical company in India and is a leading generic company in the US as well as Global Emerging Markets. Sun's high growth Global Specialty portfolio spans innovative products in dermatology, ophthalmology, and onco-dermatology and accounts for over 18% of company sales. The company's vertically integrated operations deliver high-quality medicines, trusted by physicians and consumers in over 100 countries. Its manufacturing facilities are spread across six continents. Sun Pharma is proud of its multi-cultural workforce drawn from over 50 nations. For further information, please visit and follow us on LinkedIn & X (Formerly Twitter). Disclaimer: Statements in this "document" describing Sun Pharma's objectives, projections, estimates, expectations, plans or predictions, industry conditions, or events may be "forward-looking statements" within the meaning of applicable securities laws and regulations. Actual results, performance, or achievements could differ materially from those expressed or implied. Sun Pharma does not undertake any obligation to update or revise forward-looking statements to reflect developments or circumstances that arise or to reflect the occurrence of unanticipated developments/circumstances after the date hereof. SOURCE Sun Pharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期临床结果临床2期

2024-09-13

·精准药物

生物电子等排体不对称合成研究及在药物研发中应用

芳香环广泛存在于天然产物与生物活性化合物中，具有的限制分子构象，通过非共价相互作用增强对受体结合能力，通过交叉偶联反应构建丰富化合物库的特点。但同时富含π电子的芳环易氧化，严重降低代谢稳定性。此外，与C( sp3 )分子相比，芳香族分子的水溶性降低，log D增加 (导致脱靶概率增加)，阻碍了药物研发。基于 C( sp3 ) 的双环烃骨架作为芳香环的等排体，可以作为芳环的替代品。经过适当设计，这些分子骨架可以保留苯环的构象限制和生物活性，并增强生物物理性质。这种等排体取代方法具有两个重要特点。第一是保留现代催化交叉偶联方法所伴随的高效、可靠、模块化和可扩展的合成技术。第二是给予配体立体化学性质。由于大多数生物相关受体是手性的，非对称电子等排体的可能通过锁钥原理增强与其同源受体的结合。如MK-5108 与有丝分裂激酶 Aurora A 的非活性 DFG-out 状态结合时，如果它在受体上部区域占据的体积比下部区域更大，则预计结合效果更好。此外已证实随着化合物中手性中心数量的增加，配体混杂性会降低。目前缺乏从易得前体合成这种等排体的简单、可扩展以及催化对映选择性好的方法。来自美国波士顿大学的研究人员通过合成化学与计算技术交叉研究，描述了一种反应，它保留了当代交叉偶联的优势，并允许将简单的起始材料转化为对映体富集的3,5-二取代三环庚烷骨架，具有与间位二取代苯环相似的空间构象。该反应在低负载的手性钯配合物下发生，并产生可塑的含硼电子等排体，具有进一步改性的巨大潜力。双环庚二烯1在添加合适的亲电试剂后很容易转化为三环庚烷骨架2。双环有机金属化合物3的类似亲电活化可以导致闭环 C-C 键形成，从而转化为三环庚烷骨架。在此基础上，他们证明将合成2和4中的汞盐替换为钯配合物并与有机亲电试剂结合时，可以进行三环庚烷的催化合成，同时亲电试剂被添加到骨架中。在催化量的 Pd(OAc) 2和手性配体L1存在下，二硼底物5和有机亲电试剂参与催化对映选择性环合生成三环庚烷，具有高产率和对映选择性。缺电子和富电子亲电试剂都可以轻松获得产物，并可以扩展到杂环和非芳香族亲电试剂，未保护的苯胺和苯酚也不会干扰反应。化合物5可以直接由廉价的市售降双环庚二烯和B2(pin)2以多克规模制备。5的反应可以在5 mmol的规模上进行，仅需0.5 mol％的钯配合物，经过24小时的反应就可以以良好的产率完成。产物7中的硼酸酯可以通过交叉偶联进行烯丙基化、羧化、胺化和转化为衍生醇等，便于构建丰富的间位二取代苯等排体化合物库。接下来他们对反应的机理进行了研究，密度泛函理论计算用于确定GS0的反应路径的自由能曲线。在路径A中，TS1a的carbopalladation产生中间体GS1a，接下来有机硼作为亲核试剂同时排出和还原金属。在路径B中，TS1b通过nucleopalladation生成GS1b，然后直接进行还原消除得到产物。计算表明，carbopalladation的能量较低，烯烃迁移插入生成GS1a所需的能垒比nucleopalladation低得多 (0.7 kcal mol−1对18.7 kcal mol−1）。计算TS1a产生的13C动力学同位素效应 (KIE) 与通过 Singleton 方法实验确定的结果非常吻合。最值得注意的是5在C2处表现出可忽略不计的 KIE，这与carbopalladation机理一致。此外进行了计算研究以阐明对映体诱导的起源。计算出的导致次要产物立体异构体的过渡态结构将 CH 2双环庚烷结构单元的桥直接位于空间受阻的蒽环体系之下，而主要异构体的过渡态构象避免了这种相互作用。为了确定三环庚烷骨架是否适合用于生物活性分子，研究人员将33的两种对映体制备为脂肪酸酰胺水解酶(FAAH)抑制剂URB597的手性等排类似物，并进行分析。等排类似物具有与URB597相似的分子量，在水缓冲液中的溶解度增加10倍，同时保持了相当的亲脂性。此外，通过小鼠肝微粒体测定发现等排类似物相对URB597表现出明显增加的代谢稳定性。研究人员还通过定量基于活性的蛋白质分析实验比较了化合物 (R,S)-33和(S,R)-33。用不同浓度的每种化合物处理小鼠脑匀浆。标记的蛋白质在链霉亲和素珠上富集，并通过基于定量串联质谱标记的质谱法进行分析。等排类似物的效力不如URB597，但保留了抑制FAAH的能力。此外，电子等排体的加入不会改变URB597的蛋白质组范围选择性，这两种电子等排体对FAAH都保持了比其他23种检测到的丝氨酸水解酶更高的选择性。在第二个比较分析中，对映体三环烷(S,R)-34和(R,S)-34被制备为Hedgehog通路抑制剂sonidegib的类似物。等排体的溶解度具有较大的提升，尽管其代谢稳定性有所下降。他们使用双荧光素酶测定法在Shh-LIGHT2细胞中通过三次独立的 IC50测定对立体异构体等排体进行了比较，发现对映体 sonidegib 类似物以亚微摩尔效力抑制信号传导。总的来说，该研究提供了一种合成代替间位二取代苯的非芳香等排体的不对称催化反应。该反应在钯催化下将二环庚二烯转化为一种含有手性硼酸脂的三环庚烷，并且可以进一步利用硼基团发生交叉偶联生成更加丰富的化合物。反应路线简单廉价，具有很好的对映异构选择性和产率，也能够适应于多种类型的基团，同时具有改善物化性质的潜力，为药物开发提供新的策略。参考文献 1. Zhang, M., Chapman, M., Sarode, B.R. et al. Catalytic asymmetric synthesis of meta benzene isosteres. Nature (2024). 2. Wiesenfeldt, M.P., Rossi-Ashton, J.A., Perry, I.B. et al. General access to cubanes as benzene bioisosteres. Nature 618, 513–518 (2023). 声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

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外链

KEGG	Wiki	ATC	Drug Bank
D10729	磷酸索立德吉	L01XX48	DB09143

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适应症	国家/地区	公司	日期
转移性基底细胞癌	澳大利亚	Sun Pharma ANZ Pty Ltd.	2015-08-10
基底细胞癌	美国	Sun Pharmaceutical Industries Ltd.	2015-07-24

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适应症	最高研发状态	国家/地区	公司	日期
基底细胞痣综合征	临床3期	比利时	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	加拿大	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	捷克	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	芬兰	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	德国	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	希腊	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	意大利	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	西班牙	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	瑞士	Novartis Pharmaceuticals Corp.	2017-03-03
基底细胞痣综合征	临床3期	英国	Novartis Pharmaceuticals Corp.	2017-03-03

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临床结果

适应症

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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


NCT04066504 (NISSO, Pubmed \| BMC Cancer)	N/A	基底细胞癌	321	Sonidegib 200 mg	鑰鏇衊築簾壓襯選糧廠(齋鏇衊膚夢醖網蓋製廠) = Most TEAEs were ≤ grade 2 and the most common were muscle spasms (43.9%), dysgeusia (37.1%), and alopecia (30.2%) 製夢繭窪遞繭膚醖積廠 (簾艱艱壓願鏇構衊選艱 ) 更多	积极	2024-11-14
BOLT study (EADV2023)	临床2期	基底细胞癌	194	Sonidegib 200 mg daily	築顧構獵積齋選艱構築(憲鏇網顧簾鹹構遞網觸) = 餘積餘壓簾鑰繭觸餘遞顧繭衊鹹範願憲鏇壓壓 (構廠鬱膚網遞齋醖繭鑰, 15.1 ~ NE)	-	2023-10-11
WCD2023	N/A	-	-	Sonidegib	醖窪築襯淵糧範淵簾繭(鏇淵簾鏇範醖網憲廠顧) = 鏇鑰廠獵簾獵鏇憲鑰選襯築憲糧顧鹽窪遞壓觸 (齋壓淵鑰鏇憲選憲願憲 ) 更多	-	2023-07-05
NCT04007744 (ASCO 12023 \| ASCO 22023) 人工标引	临床1期	HR阳性/HER2低表达实体瘤 \| 非小细胞肺癌	33	Sonidegib Phosphate+Pembrolizumab	範醖膚鏇網膚衊壓構淵(繭獵齋繭積製窪觸選鬱) = 遞製繭餘網醖簾襯齋築簾願鹹遞築窪鏇壓願簾 (構憲遞網襯鏇廠鏇簾鏇 ) 更多	积极	2023-05-26
VISMONEO (EADV2022)	N/A	局部晚期鳞状细胞癌新辅助	13	Sonidegib	鑰積蓋範鹽顧範顧鑰簾(選壓網鑰築製襯繭構範) = 構鏇顧膚膚範壓觸願範蓋選壓鏇構觸遞齋醖鹹 (夢淵選艱遞醖選鏇鏇醖, 6.3 ~ 27.3) 更多	积极	2022-09-07
NCT01327053 (BOLT, Pubmed \| BMC Cancer)	临床2期	基底细胞癌	66	Sonidegib 200 mg	選廠構淵廠觸廠憲艱鏇(獵艱衊餘顧構選艱餘憲) = 壓築糧築築艱積壓鹽襯範餘齋齋鹽獵築膚鹽壓 (襯壓齋獵鑰襯遞鹽選糧 ) 更多	-	2021-11-19
NCT01327053 (BOLT, Pubmed \| Dermatol Ther (Heidelb))	临床2期	基底细胞癌	230	Sonidegib 200 mg	齋鏇選衊淵糧糧淵築鹹(餘夢壓憲齋衊網襯夢鑰) = 淵餘鏇壓選積醖製齋範壓艱鏇憲鏇鬱繭憲膚構 (簾願膚淵憲憲齋夢衊廠 )	-	2021-10-20
NCT01787552 (Pubmed \| Blood Adv) 人工标引	临床1/2期	原发性骨髓纤维化	50	sonidegib+ruxolitinib	範淵鏇醖淵淵襯艱鹽鹽(鬱範網鹽齋積積觸網鏇) = at level 2: increased blood creatine phosphokinase (grades 3 and 4, n = 1 each) 網獵獵鹹廠築蓋顧獵範 (鹹製窪遞網鑰選繭醖構 ) 更多	不佳	2020-07-14
NCT02086552 (CTgov)	临床2期	复发性浆细胞骨髓瘤 \| 难治性多发性骨髓瘤	28	Laboratory Biomarker Analysis+Lenalidomide+Sonidegib	鑰觸壓鹹淵窪網鏇壓願(築膚築鏇壓淵鏇獵顧觸) = 顧淵夢蓋膚夢網蓋繭選糧鹽獵鹽鹽觸憲顧齋選 (衊願獵積窪鑰遞醖夢窪, 遞願積鏇襯觸範糧積鏇 ~ 簾衊顧艱築願構餘選夢) 更多	-	2019-05-29
NCT02027376 (GEICAM/2012-12 (EDALINE), Pubmed \| Invest New Drugs) 人工标引	临床1期	晚期三阴性乳腺癌 triple negative	12	Docetaxel+Sonidegib Phosphate	憲鹽膚遞鹽淵夢鑰簾蓋(積鬱鬱艱廠顧艱遞憲蓋) = sonidegib 800 mg orally q.d. + docetaxel 75 mg/m2 given intravenously on day 1 of 21-day cycles 願糧積鏇齋鹹顧糧鹽襯 (繭醖艱壓顧鬱窪衊構構 ) 更多	积极	2019-02-01