主要目的：（1）定量分析健康受试者口服[14C] KL590586后排泄物中的总放射性，获得人体放射性回收率和主要排泄途径；（2）考察健康受试者口服[14C] KL590586后全血与血浆总放射性的分配比，以及全血和血浆中总放射性的药代动力学特征；（3）鉴定健康受试者口服[14C] KL590586后在血浆、尿液和粪便中的主要代谢产物，确定主要生物转化途径。次要目的：（1）采用已验证的LC-MS/MS方法定量分析血浆中KL590586及其代谢产物（如适用）的浓度，获得血浆中KL590586及其代谢产物（如适用）的药动学参数；（2）观察健康受试者单次口服[14C] KL590586后的安全性。

开始日期2023-08-29

申办/合作机构

四川科伦博泰生物医药股份有限公司

ChiCTR2300074552 / Suspended临床1期IIT

To evaluate the randomized, open-label, two-cycle, double-cross food effects of KL590586 capsules in healthy subjects in a phase I clinical trial

开始日期2023-08-21

申办/合作机构-

100 项与 Lunbotinib 相关的临床结果

登录后查看更多信息

100 项与 Lunbotinib 相关的转化医学

登录后查看更多信息

100 项与 Lunbotinib 相关的专利（医药）

登录后查看更多信息

166

项与 Lunbotinib 相关的文献（医药）

2024-12-01·Journal of computer-aided molecular design

Identifying and characterising promising small molecule inhibitors of kinesin spindle protein using ligand-based virtual screening, molecular docking, molecular dynamics and MM‑GBSA calculations

Article

作者: Elseginy, Samia A

Abstract:

The kinesin spindle protein (Eg5) is a mitotic protein that plays an essential role in the formation of the bipolar spindles during the mitotic phase. Eg5 protein controls the segregation of the chromosomes in mitosis which renders it a vital target for cancer treatment. In this study our approach to identifying novel scaffold for Eg5 inhibitors is based on targeting the novel allosteric pocket (α4/α6/L11). Extensive computational techniques were applied using ligand-based virtual screening and molecular docking by two approaches, MOE and AutoDock, to screen a library of commercial compounds. We identified compound 8-(3-(1H-imidazol-1-ylpropylamino)-3-methyl-7-((naphthalen-3-yl)methyl)-1H-purine-2, 6 (3H,7H)-dione (compound 5) as a novel scaffold for Eg5 inhibitors. This compound inhibited cancer cell Eg5 ATPase at 2.37 ± 0.15 µM. The molecular dynamics simulations revealed that the identified compound formed stable interactions in the allosteric pocket (α4/α6/L11) of the receptor, indicating its potential as a novel Eg5 inhibitor.Graphical Abstract

2024-01-11·Journal of medicinal chemistry1区 · 医学

Discovery of (2S)-N-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-3-(6-(4-cyanophenyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-hydroxy-2-methylpropanamide as a Highly Potent and Selective Topical Androgen Receptor Antagonist for Androgenetic Alopecia Treatment

1区 · 医学

Article

作者: Peng, Shaoping ; Li, Hongmei ; Pei, Sheng ; Fan, Yawen ; Tang, Renhong ; Zhao, Siqi ; Zhang, Wenqiang ; Feng, Yunrui ; Zhou, Xiaoyu ; Fu, Lingsheng ; Luo, Yi ; Jiao, Yu ; Chen, Zhuolin ; Tang, Feng ; Xie, Shaofei ; Lai, Qianlong ; Chen, Yadong ; Zhang, Yan ; Lu, Tao

Androgenetic alopecia (AGA) is the most prevalent form of progressive hair loss disorder in both men and women, significantly impacting their appearance and overall quality of life. Overactivation of the AR signaling pathway in dermal papilla cells (DPCs) plays a crucial role in the development and progression of AGA. Considering the severe systemic side effects associated with oral AR antagonists, the idea of developing of topical AR antagonists with rapid metabolic deactivation properties emerged as a promising approach. Herein, through systematic structural optimization, we successfully identified compound 30a as a potent and selective AR antagonist with favorable pharmacokinetic properties, resulting in high skin exposure and low plasma exposure following topical administration. Importantly, in both hair-growth and AGA mouse models, compound 30a showed potent hair-growth-promoting effects without any noticeable toxicity. These findings suggest that compound 30a holds significant potential as a topical AR antagonist for treating AGA patients.

2023-12-12·ACS omega

Efficient Protocol for Novel Hybrid Pyrimidines Synthesis: Antiproliferative Activity, DFT Analyses, and Molecular Docking Studies

Article

作者: Hussein, Modather F ; Ghoneim, Amira A ; Althobaiti, Ibrahim O ; Alserhani, Mjd Saleh Morezeq ; Ibrahim, Hamada Mohamed ; Arafa, Wael A A ; Mourad, Asmaa K

An efficient, microwave/ultrasound-irradiated synthesis of novel chromenopyrimidines has been established. 2-Amino-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (1) underwent cyclization reactions with various assorted reagents under sustainable conditions to afford a family of fused pyrimidine derivatives. The proposed structures of the designed fused pyrimidines were confirmed by several spectral techniques. Moreover, the targeted pyrimidines were estimated for their in vitro cytotoxic activities toward three carcinoma cell lines: breast (MCF7), hepatocyte (HepG2), and lung (A549) cancer cell lines, as well as one noncancerous cell line (MCF-10A). Structure-activity relationship (SAR) analyses revealed that derivatives 3 and 7 exhibited the highest potency in inhibiting the growth of cancer cells tested in vitro. Particularly, 3-amino-4-imino-5-(thiophen-2-yl)-3,4,5,7,8,9-hexahydro-6H-chromeno[2,3-d]pyrimidin-6-one (3) displayed a robust impact with IC₅₀ values ranging from 2.02 to 1.61 μM. Interestingly, compound 3 was observed to have low cytotoxicity toward noncancerous cell (MCF-10A) compared to the standard drug (Doxorubicin). Further, quantum chemical computations of the designed molecules utilizing density functional theory (DFT) were conducted and shown to be compatible with the observed antiproliferative properties. Thorough docking investigations revealed that the assembled compounds possess exceptionally low binding energies toward our three selected proteins: 4b3z-Lung, HepG2-2JW2, and 6ENV-MCV-7. Based on these intriguing results, compound 3 could be further evaluated for preclinical screening, potentially paving the way for its utilization as a promising cancer treatment.

项与 Lunbotinib 相关的新闻（医药）

2024-09-19

·药渡

恒瑞、石药、科伦老牌药企押注创新，创新药将成增长新引擎

来源：药渡撰文：书本滑编辑：维他命近日，2024年（第41届）全国医药工业信息年会暨2023年度中国医药工业百强榜单发布会在成都盛大开幕，会上发布了备受行业关注的2023年度中国医药工业百强企业榜单及系列榜单。恒瑞荣膺“2024年中国医药研发产品线最佳工业企业”榜单榜首，科伦（NO.4）、石药（NO.10）入选该榜单Top10。 PART. 01 恒瑞：创新药营收占比超50% 恒瑞2024上半年营收、净利润、扣非后净利润分别为136亿元、34.3亿元、34.9亿元，同比分别增长21.78%、48.76%、55.58%。创新药方面，自2011年首个创新药艾瑞昔布上市以来，至报告期公司共已上市16款创新药，其中14款为自主研发，2款为引进（林普利塞、奥特康唑）。 2024 年上半年公司创新药收入达66.12亿元（含税，不含对外许可收入），创新药出海取得成效，成为业绩增长的第二引擎。报告期内，公司已将收到的Merck Healthcare 1.6亿欧元对外许可首付款确认为收入。加上许可收入，创新药营收占比已超50%，公司的创新转型已基本完成，根据创新药的上量特点，未来创新药占比会更大。在研品种方面公司持续加大创新力度，维持较高的研发投入，报告期内公司累计研发投入38.60亿元，其中费用化研发投入30.38亿元。至报告期内，2款品种申请NDA，10款品种进入临床III期，20款品种进入临床II期，19款品种进入临床I期。其中在ADC方面，有12个新型、具有差异化的ADC分子成功获批临床，HER2 ADC产品SHR-A1811、TROP2 ADC产品SHR-A1921及CLAUDIN18.2 ADC产品SHR-A1904快速进入临床Ⅲ期研究阶段。基于PROTAC技术平台，有2个PROTAC分子已处于临床研究阶段；PD-L1/TGFβ融合蛋白药物SHR-1701快速推进多个临床Ⅲ期研究。另外恒瑞也在积极布局PROTAC、单/双抗体、ADC、小核酸、核药、多特异性抗体、双抗ADC等前沿技术平台。 PART. 02 石药：押注创新约60项在研药物创新高石药2024年上半年营收162.84亿元，同比增长1.3%，股东应占溢利约30.2亿元，同比增长1.8%。石药按业务类别分为成药业务，原料业务及功能食品三大部分。分业务看，成药业务报告期内录得收入135.49亿元，同比增长4.8%，占总营收的83%。石药目前已上市创新药主要集中在中枢神经系统和抗肿瘤领域，中枢神经系统报告期内营收52.36亿元，肿瘤营收26.83亿元，分别占成药收入的38.6%、19.8%。公司的大单品恩必普（丁苯酞软胶囊、丁苯酞氯化钠注射液）为1类新药，用于脑卒中，2005年软胶囊剂型获批上市，2010年注射液上市。2020年至2023年，丁苯酞的销售额均超过60亿元大关。在肿瘤领域，上市的创新药有：津优力（聚乙二醇化重组人粒细胞刺激因子注射液）、多恩达（米托蒽醌脂质体注射液）、津立泰（纳鲁索拜单抗注射液）。津优力是中国首个自主研发的长效升白药物，用于预防和治疗化疗患者因中性粒细胞减少而引起的感染和发热，为治疗用生物制品1类新药；多恩达以2类开发，为全球首个上市的米托蒽醌脂质体；津立泰是首个IgG4 RANKL抑制剂，用于不可手术切除或手术切除可能导致严重功能障碍的骨巨细胞瘤成人患者，于2023年9月由NMPA批准。另外，公司仿制上市了多款脂质体和白蛋白品种，紫杉醇白蛋白、多柔比星脂质体、伊立替康脂质体等，可以说石药是脂质体领域当之无愧的一线梯队。在研品种方面 2024年上半年研发费用25.42亿元，同比增长10.3%，约占成药业务收入18.8%。目前逾60个重点在研药物已进入临床或申报阶段，其中7个已递交上市申请，19个产品（22个适应症）处于注册临床阶段。同时，公司积极布局纳米制剂、信使核酸(mRNA)、小干扰核酸（siRNA）、抗体/融合蛋白、细胞治疗、抗体药物偶联物（ADC）等八大技术创新研发平台，为创新药物的研发提供了强大的支持。目前在研项目约130项，其中大分子40余项、小分子40余项、新型制剂40余项。 PART. 03 科伦：重点布局合成生物学与ADC 2024年上半年营收118.27亿元、净利润为18亿元、扣非后净利润17.53亿元，同比分别增长9.52%、28.24%、29.78%。业务方面，公司形成科伦药业+川宁生物+科伦博泰+锐康生物的业务矩阵，川宁生物重点聚焦中间体和原料药等的生产业务，科伦博泰聚焦创新药的开发，瑞康生物负责合成生物学前期的研究开发，后期合成生物学的生产由川宁生物承接。合成生物学方面，锐康生物在前期已构建4类底盘菌和化合物等平台，目前锐康生物完成了化妆品活性原料RCB112角鲨烷、饲料添加剂RCB114肌醇、保健品原料 RCB108褪黑素等产品的菌种构建、小试发酵和提取工艺的优化，部分产品已经在川宁生物进行试生产。中长期主要聚焦在大宗或产值较高的二类产品的研发上。首个合成生物学产品红没药醇（舒瑞宁）荣获InnoCosme Awards美耀原料奖，这是化妆品行业的专业奖项，标志着公司合成生物学业务发展取得了重大成果。创新药方面，公司目前在研项目30余项，聚焦于肿瘤学与免疫领域，sacTMT、A166、SKB315、SKB410、A167、A140、A400等品种推进至临床阶段。 Sac-TMT是由科伦博泰开发的靶向TROP2的人源化单克隆抗体、可酶促裂解的Linker和新型拓扑异构酶 I 抑制剂组合而成的新一代抗体偶联药物（ADC），sac-TMT目前正在开展针对多个瘤种的单药/联用的2期和3期临床试验。sac-TMT大中华区以外的商业化权益已授权给默沙东，截至2024年6月30日，默沙东已启动十项sac-TMT作为单药疗法或联合帕博利珠单抗或其他药物用于多种适应症的全球3期临床研究。 A166已达到其针对三线及以上晚期HER2+BC的关键2期试验的主要终点，相关NDA已于2023年5月获NMPA受理。另外正在中国开展一项针对二线及以上晚期HER2+BC的3期试验。SKB315（CLDN18.2-ADC）已在中国开展了SKB315针对晚期实体瘤患者的1a期临床试验。 A167（塔戈利单抗）于2021年11月向NMPA递交NDA申请，以将A167作为复发或转移性鼻咽癌（RM-NPC）的三线及以上治疗药物上市。2024年5月，A167一线治疗NPC的注册性3期研究NDA已获NMPA受理。A140用于治疗RAS野生型转移性结直肠癌（mCRC）及头颈部鳞状细胞癌（HNSCC）的NDA已于2023年9月获得NMPA受理。科伦博泰在ADC领域可以说具有全球前沿水平的研发实力，科伦博泰的新型双抗ADC SKB571也已推进至临床阶段，SKB571是一款新型双抗ADC，主要针对肺癌、消化道肿瘤等多种实体瘤。通过科学的靶点组合选择和差异化的双抗分子设计，提升对肿瘤的靶向性，并有利于克服肿瘤异质性，提升疗效；通过搭配OptiDC™平台的高亲水性毒素－连接子策略，该产品不仅DAR值均一，并且展现了良好的体内药代动力学性质。临床前研究显示，该产品在多种人源肿瘤异种移植（PDX）模型和食蟹猴中，分别展现了良好的抗肿瘤效果及安全性。该产品将于近期递交IND申请。 PART. 04 小结对于老牌传统药企，过去十年是转型创新的重要阶段，恒瑞已出现创新药营收占比超50%的创新拐点，对于创新转型的传统药企，过去十年已完成最困难最昂贵的研发投入阶段，未来会不断兑现创新受益。对于老牌药企来说，下一阶段的挑战是成为具有国际竞争力的Big Pharma。 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！偶联不止ADC，浅谈新型偶联药物——AOC 一年两针超长效降脂药「英克司兰」：小核酸药物的璀璨新星 2024生物制药裁员潮：人数激增、肿瘤及神经病学成重灾区……

临床3期抗体药物偶联物蛋白降解靶向嵌合体财报申请上市

2024-09-13

·Business Wire

Guardant Health to Share Data at ESMO 2024 Further Demonstrating Strong Performance of Its Precision Oncology Technology in Multiple Advanced Tumor Types

PALO ALTO, Calif.--( BUSINESS WIRE )--Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, today announced the company and its research collaborators will present data from several studies utilizing Guardant technology to advance precision oncology at the European Society for Medical Oncology Congress (ESMO) in Barcelona, Spain, Sept. 13-17, 2024. Data on the Guardant Reveal™ minimal residual disease test in locally advanced rectal cancer patients enrolled in the NO-CUT trial will be presented in a proffered paper session during Presidential Symposium III. Other presentations will include findings from studies evaluating Guardant360® for therapy selection in advanced breast cancer and other solid tumors, and the Guardant Infinity™ platform for response monitoring in advanced non-small cell lung cancer (NSCLC). “Our latest data featured at ESMO further highlight the value of Guardant’s technology in precision oncology and the critical role liquid biopsy can play in informing therapy selection and treatment management across multiple tumor types,” said Craig Eagle, M.D., chief medical officer at Guardant Health. “We look forward to sharing how Guardant tests can contribute to improved outcomes across all stages of cancer care.” Complete list of Guardant Health and collaborator presentations at ESMO 2024 Abstract Title (Hall 6, unless otherwise noted) Product Saturday, September 14 | 9:00 - 17:00 1295P EP0031 a next-generation selective RET inhibitor (SRI): Correlation of molecular and clinical responses in patients with RET alteration positive solid tumours naïve to or following prior SRI Guardant Infinity Sunday, September 15 | 9:00 - 17:00 127P Clinical utility of circulating tumor DNA (ctDNA) next generation sequencing (NGS) to inform treatment decisions for patients (pts) with advanced solid tumors Guardant 360 Monday, September 16 | 9:00 - 17:00 418P Concordance of PI3K-AKT pathway alterations between tumor and ctDNA in metastatic breast cancer Guardant 360 419P Prevalence of gene rearrangement on ctDNA NGS and its targetability in patients with advanced breast cancer Guardant 360 Monday, September 16 | 17:04 – 17:16 509O Total neoadjuvant treatment (TNT) with non-operative management (NOM) for proficient mismatch repair locally advanced rectal cancer (pMMR LARC): first results of NO-CUT Trial Proffered Paper Session: Presidential Symposium III: Eyes to the future, Barcelona Auditorium, Hall 2 Guardant Reveal The full abstracts for Guardant Health and a list of all abstracts being presented at the ESMO Congress can be found on the ESMO website . For information and updates from the conference, follow Guardant Health on LinkedIn , X (Twitter) and Facebook or visit Guardant on-site at booth #510. About Guardant Health Guardant Health is a leading precision oncology company focused on guarding wellness and giving every person more time free from cancer. Founded in 2012, Guardant is transforming patient care and accelerating new cancer therapies by providing critical insights into what drives disease through its advanced blood and tissue tests, real-world data and AI analytics. Guardant tests help improve outcomes across all stages of care, including screening to find cancer early, monitoring for recurrence in early-stage cancer, and treatment selection for patients with advanced cancer. For more information, visit guardanthealth.com and follow the company on LinkedIn , X (Twitter) and Facebook . Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential utilities, values, benefits and advantages of Guardant Health’s liquid biopsy tests or assays, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect Guardant Health’s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” and elsewhere in its Annual Report on Form 10-K for the year ended December 31, 2023, and in its other reports filed with or furnished to the Securities and Exchange Commission thereafter. The forward-looking statements in this press release are based on information available to Guardant Health as of the date hereof, and Guardant Health disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Health’s views as of any date subsequent to the date of this press release.

ASCO会议临床研究

2024-06-18

·米内网

【重磅】科伦1类新药来袭，猛攻2200亿市场

精彩内容 6月18日，科伦药业发布公告称，注射用SKB518获批临床，该产品是公司今年首个获批临床的1类新药。在抗肿瘤和免疫调节剂这个千亿市场，科伦药业有3款1类新药正在冲刺上市，6款1类新药在开展临床。公告中提到，注射用SKB518是一款创新抗体偶联药物，在临床前展现了良好的有效性和安全窗，拟用于治疗晚期实体瘤。近几年，科伦药业的新药研发不断迎来好消息，目前3款生物药1类新药正在冲刺上市，均属于抗肿瘤和免疫调节剂。图1：科伦药业申报上市并在审的1类新药情况来源：米内网中国申报进度（MED）数据库塔戈利单抗注射液是一款PD-L1单抗，在2021年11月首次提交上市申请，用于治疗鼻咽癌，该新药有望成为公司首款获批的生物药1类新药。注射用A166是一款靶向HER2的创新抗体偶联药物，也是科伦药业首个提交上市申请的ADC药物。该新药在2023年5月提交了用于既往经二线及以上抗HER2治疗失败的HER2阳性不可切除的局部晚期、复发或转移性乳腺癌的上市申请。注射用SKB264是一款靶向TROP2的创新ADC，该新药在2023年12月提交了用于既往至少接受过2种系统治疗（其中至少1种治疗针对晚期或转移性阶段）的不可切除的局部晚期或转移性三阴性乳腺癌（TNBC）成人患者的上市申请。该新药有望成为中国首个获批上市的国产创新TROP2-ADC。图2：中国三大终端六大市场抗肿瘤和免疫调节剂的销售情况（单位：万元）来源：米内网格局数据库米内网数据显示，2023年在中国三大终端六大市场（统计范围见文末）抗肿瘤和免疫调节剂的合计市场规模已超过了2200亿元，近三年保持正增长态势，潜力不容小觑。表1：科伦药业已开展临床的1类新药情况注：已终止项目不纳入统计来源：米内网中国临床试验数据库目前，科伦药业在研的1类新药中有多个涉及抗肿瘤领域，包括了化药1类新药KL590586胶囊和KL340399注射液，生物药1类新药注射用SKB410、注射用SKB315、SKB337注射液、KL-A289注射液，上述新药均在I期临床阶段，后续有望为公司抢攻千亿市场添新动力。资料来源：公司公告、米内网数据库注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至6月18日，如有疏漏，欢迎指正！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 【分享、点赞、在看】点一点不失联哦

抗体药物偶联物申请上市临床1期引进/卖出上市批准

100 项与 Lunbotinib 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床2期	中国	四川科伦药物研究院有限公司	2021-06-01
RET突变阳性甲状腺髓样癌	临床申请批准	中国	四川科伦博泰生物医药股份有限公司	2023-07-24

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05443126 (Phase-1 dose escalation and expansion study of EP0031, ASCO2024)	临床1/2期	非小细胞肺癌	27	EP0031 60mg QD	艱獵遞艱艱繭網窪壓鏇(鹽遞繭窪淵網壓遞網網) = No DLTs were observed 網願夢鑰觸廠範艱構鏇 (艱壓醖築願選鹽觸獵淵 ) 更多	积极	2024-05-24
	临床1/2期	非小细胞肺癌	27	EP0031 90mg QD		积极	2024-05-24
NCT05265091 (KL400-I/Ⅱ-01, ASCO2023) 人工标引	临床1期	RET突变实体瘤 RET Fusion	87	KL590586	餘鑰襯餘願簾淵憲顧製(繭醖顧淵蓋壓獵簾鏇鏇) = Not reached 餘願襯齋襯製繭鹹齋簾 (鹽鏇構簾夢糧蓋鹹顧蓋 ) 更多	积极	2023-05-31