Phase Ib IIT of Heat Shock Protein 90 Inhibitor TAS-116 Combined with Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Advanced Breast Cancer Progressing on Palbociclib & Treatment-refractory Solid Tumors with Retinoblastoma Deficiency

The purpose of this study is to evaluate the safety and efficacy of TAS-116 with palbociclib in two groups of patients:
* Patients with advanced breast cancer that has become worse after taking palbociclib alone
* Patients with cancers that have an abnormality in a gene called the "retinoblastoma gene".

开始日期2023-09-12

申办/合作机构

Brown University

CTR20232143 / Recruiting临床1期

一项TAS-116(pimitespib)联合伊马替尼治疗晚期胃肠道间质瘤患者的Ⅰ期研究

这是一项I期、开放性、多国、多中心研究。在中国患者剂量递增部分，将在中国患者中评估pimitespib单药治疗以及与伊马替尼联合治疗的安全性和耐受性。

开始日期2023-09-04

申办/合作机构

Bushu Pharmaceuticals Ltd.

[+2]

JPRN-jRCT2031230263 / Recruiting临床2期

Phase 2 platform study evaluating combination therapy with TAS-116 (pimitespib) in patients with malignant tumors - CHAPTER-Platform-201

开始日期2023-08-25

申办/合作机构

Sato Atsushi

100 项与 Pimitespib 相关的临床结果

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100 项与 Pimitespib 相关的转化医学

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100 项与 Pimitespib 相关的专利（医药）

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项与 Pimitespib 相关的文献（医药）

2024-10-01·LIFE SCIENCES

Modulating the HSP90 control over NFκB/NLRP3/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: Insights into the role of TAS-116 (Pimitespib)

Article

作者: Hamad, Rabab S ; Khalifa, Amira Karam ; Elmorsy, Elsayed A ; Ahmed, Syed Suhail ; AlSalloom, A A ; Abdel-Reheim, Mustafa Ahmed ; Amer, Maha M ; Abdel-Hamed, Mohamed R ; Alibrahim, Alaa Oqalaa E ; Saber, Sameh ; Abozaid, Lobaina ; Taha, Hagir Hussein ; Alkhamiss, Abdullah S ; Mohamed, Nahla B ; Nadwa, Eman Hassan ; Nour-El-Din, M ; Mostafa-Hedeab, Gomaa ; Mohamed, Enas A

Aberrant activation of the NLRP3 inflammasome is recognized to induce a chronic inflammatory response in the liver, ultimately leading to hepatic fibrosis. HSP90 is suggested to regulate NLRP3 activation and its downstream signaling. This study is the first to explore the potential therapeutic role of pimitespib in mitigating liver fibrosis in rats. The results of the study revealed that pimitespib effectively suppressed hepatic inflammation and fibrogenesis by modulating HSP90's control over the NFκB/NLRP3/caspase-1 axis. In vitro experiments demonstrated that pimitespib reduced LDH levels and increased hepatocyte survival, whereas in vivo, it prolonged the survival of rats with hepatic fibrosis. Additionally, pimitespib exhibited improvements in the function and microscopic characteristics of rat livers. Pimitespib effectively inhibited NFκB, which serves as the priming signal for NLRP3 activation. Pimitespib's inhibitory effect on NLRP3, identified as an HSP90 client protein, plays a central role in the observed anti-fibrotic effect. The simultaneous inhibition of both priming and activation signals of NLRP3 by pimitespib led to a reduction in caspase-1 activity and subsequent suppression of the N-terminal fragment of gasdermin D, ultimately constraining hepatocyte pyroptotic cell death. These diverse effects were associated with a decrease in the transcription of inflammatory mediators IL-1β, IL-18, and TNF-α, as well as the fibrogenic mediators TGF-β, TIMP-1, PDGF-BB, and Col1a1. Moreover, pimitespib induced the expression of HSP70, which could further contribute to the repression of fibrosis development. In summary, our findings provide an evolutionary perspective on managing liver fibrosis, positioning pimitespib as a promising candidate for anti-inflammatory and antifibrotic therapy.

2024-09-26·JOURNAL OF MEDICINAL CHEMISTRY

Targeting HSP90 for Cancer Therapy: Current Progress and Emerging Prospects

Review

作者: Chen, Ruixian ; Wang, Chengdi ; Wang, Yuxi ; Zhang, Jifa ; Liang, Xinqi

Heat shock protein 90 (HSP90), a highly conserved member of the heat shock protein family, regulates various proteins and signaling pathways involved in cancer, making it a promising target for cancer therapy. Traditional HSP90 inhibitors have demonstrated significant antitumor potential in preclinical trials, with over 20 compounds advancing to clinical trials and showing promising results. However, the limited clinical efficacy and shared toxicity of these inhibitors restrict their further clinical use. Encouragingly, developing novel inhibitors using conventional medicinal chemistry approaches─such as selective inhibitors, dual inhibitors, protein-protein interaction inhibitors, and proteolysis-targeting chimeras─is expected to address these challenges. Notably, the selective inhibitor TAS-116 has already been successfully marketed. In this Perspective, we summarize the structure, biological functions, and roles of HSP90 in cancer, analyze the clinical status of HSP90 inhibitors, and highlight the latest advancements in novel strategies, offering insights into their future development.

2024-08-01·ANTICANCER RESEARCH

Pimitespib, a Novel Heat Shock Protein 90 Inhibitor, Is Effective in Treating Renal Cell Carcinoma by Anti-angiogenetic Signaling

Article

作者: Makino, Tomoki ; Takahashi, Tsuyoshi ; Yamamoto, Kazuyoshi ; Momose, Kota ; Teranishi, Ryugo ; Eguchi, Hidetoshi ; Yamashita, Kotaro ; Doki, Yuichiro ; Kurokawa, Yukinori ; Nakajima, Kiyokazu ; Saito, Takuro ; Tanaka, Koji

BACKGROUND/AIM:

Most clear cell renal cell carcinomas (ccRCCs) have a dysfunctional von Hippel-Lindau tumor suppressor protein (VHL). Hypoxia-inducible factors 1 and 2 alpha (HIF1α and HIF2α) accumulate in ccRCC with dysfunctional VHL and up-regulate the vascular endothelial growth factor (VEGF) pathway and tumor angiogenesis. Recently, pimitespib (PIM), a potent ATP-competitive inhibitor of heat shock protein 90 (HSP90), was developed. PIM down-regulates the expression of HIF, a key protein in ccRCC progression, with anti-angiogenic effects. This study aimed to examine the effectiveness of PIM in ccRCC and the underlying mechanisms.

MATERIALS AND METHODS:

The efficacy and mechanism of PIM against ccRCCs was evaluated using ccRCC cell lines.

RESULTS:

PIM inhibited the VEGFR pathway by down-regulating VEGFR 2, phosphorylated VEGFR 2, and protein levels in downstream signaling pathways. The growth of ccRCC cell lines was inhibited by PIM. Furthermore, PIM inhibits HIF1α, HIF2α, and VEGF expression, suggesting that PIM may suppress angiogenesis in addition to the VEGFR pathway.

CONCLUSION:

PIM provides a novel approach for treating ccRCC and holds promise for future clinical strategies. Further in vivo and clinical research is required to elucidate the detailed relationship between the effects of PIM and ccRCC.

项与 Pimitespib 相关的新闻（医药）

2024-11-14

·ioncology

2024 ESMO ASIA丨一文纵览上消化道肿瘤领域精彩壁报！

编者按 2024年欧洲肿瘤内科学会亚洲年会（ESMO ASIA 2024）将于当地时间12月6~8日在新加坡召开，届时将公布多项全球及亚太地区的最新科研和临床进展，进一步推动领域内的学术交流。目前大会官网已披露了摘要标题，《肿瘤瞭望消化时讯》特此整理了食管癌、胃癌、胰腺癌等上消化道肿瘤领域的摘要标题，带您快速浏览大会的精彩资讯！胃癌 183P-HER2过表达或无过表达时胃腺癌对新辅助化疗的反应：一项前瞻性观察研究作者：Pratap K.Deb（印第安纳州加尔各答） 157P-腹膜转移胃癌分化轨迹和耐药特征的单细胞表征作者：Haoxin Peng（中国北京） 158P-SOX方案联合伊尼妥单抗一线治疗HER2阳性晚期胃癌的最新疗效与安全性作者：Ying Kong（中国济南） 159P-B细胞的空间组织在胃癌预测和预后中的作用作者：Ryan Tay（新加坡） 160P-胃癌腹膜转移的腹膜生态位进化和微环境重塑作者：Joseph J.Zhao（新加坡） 161P-评估口服维生素B12治疗胃癌患者全胃切除术后维生素B12缺乏症的多中心随机对照试验的Ⅱ期研究作者：Three Aoyama（日本横滨） 162P-围手术期FLOT治疗胃癌和胃食管交界处癌实现PCR的疗效：单机构经验的回顾性分析作者：Xue Ru Ting（乔治市，MY） 163P-腹腔镜辅助胃切除术和常规胃切除术胃癌患者术后饮食摄入量的比较作者：Junya Morita（日本横滨） 164P-一项评估安罗替尼联合特瑞普利单抗作为一线方案治疗PS 2晚期胃癌患者的疗效和安全性的开放标签、单臂、Ⅱ期试验作者：刘可（中国上海） 165P-局部晚期胃癌新辅助治疗后病理完全缓解的预后分析：一项全国性、多中心、回顾性研究作者：Jie Chen（中国上海） 166P-幽门螺杆菌感染胃癌样本中CHOP、GRP94和干性状态之间的相互作用作者：Fatemeh Alizadeh（马什哈德，爱尔兰） 167P-与老年Ⅱ/Ⅲ期胃癌患者早期复发相关的因素：一项回顾性队列研究作者：Yu-Hsuan Shih（台中市） 168P-肌肉减少症作为接受手术和辅助化疗的Ⅱ~Ⅲ期胃癌患者的预后指标作者：Jeong Eun Kim（韩国光明） 169P-真实世界研究中PD-1抑制剂、曲妥珠单抗和一线化疗治疗HER-2阳性晚期胃癌的疗效和预后作者：刘宝瑞（中国南京） 170P-通过多模式血浆游离DNA分析鉴别恶性和良性胃病变作者：Ho D.Vo（越南胡志明市） 171P-一项关于80岁及以上Ⅱ/Ⅲ期胃癌患者辅助S-1化疗的多中心调查作者：Ai Harinauchi（日本） 172P-环状RNA谱确定circATXN1失调可作为胃癌的一个增殖因子和预后标志物作者：Jie Chen（中国上海） 173P-胃腺癌位置重要吗？来自单个肿瘤中心的回顾性研究作者：Alaaeldin Shablak（英国南安普敦） 175P-副干酪乳杆菌ZJUZ2-3通过3-IAA抑制NF-κB通路来抑制胃肿瘤发生作者：Rui Yang（中国杭州） 176P-DHX9及其靶基因AURKA通过PI3K/AKT和TNF信号通路在胃癌中的功能和机制作者：Zuhua Chen（中国武汉） 177P-HGF介导的MAP17在胃癌细胞增殖和转移中的重要作用作者：ByeongIl Jang（韩国大邱）食管癌 178P-KEYNOTE-859研究更新：帕博利珠单抗+化疗治疗晚期HER2阴性胃癌或胃食管结合部（G/GEJ）癌作者：Lina Yin（美国凯尼尔沃思） 179P-个性化微小残留病分析可预测接受根治性放疗的食管癌的预后作者：Lin-Rui Gao（中国北京） 180P-微创海绵细胞学检查在食管鳞状细胞癌和胃贲门腺癌筛查中的应用评估作者：Zhiyuan Fang（中国北京） 181P-围手术期亚叶酸、奥沙利铂、多西紫杉醇和S-1（LOTS）治疗局部晚期胃癌或胃食管结合部腺癌的疗效、安全性及游离DNA分析：一项前瞻性Ⅱ期试验作者：Chih Chieh Yen（台南市中环） 182P-东亚地区HER2阳性局部晚期或转移性胃或胃食管结合部腺癌患者的真实世界治疗模式作者：Do-Youn Oh（韩国首尔） 144P-辅助放化疗在食管角化鳞状细胞癌治疗中的作用作者：Mohamed Z.Elkarany（亚历山大市，EG） 186P-每周对比每月新辅助顺铂和氟尿嘧啶放化疗方案在局部区域食管鳞状细胞癌中的疗效和安全性作者：Cheng-Lun Lai（台湾台中市） 187P-卡瑞利珠单抗在晚期食管癌中的有效性、安全性和使用模式：基于来自三项前瞻性观察性队列研究的987例患者的个体病例数据（IPD）汇总分析作者：鲁智豪（中国北京） 188P-原发肿瘤和淋巴结病理消退对新辅助化疗免疫治疗后局部晚期食管鳞状细胞癌患者复发和生存率的影响作者：Yixin Li（中国南京） 189P-NC18（一种新型HER2靶向ADC）对Enhertu耐药CDX模型的优越的抗肿瘤活性作者：Zhi Li（中国北京） 190P-替雷利珠单抗治疗食管癌的系统评价和荟萃分析作者：Hashim Talib Hashim（Karbala） 191P-来自印度南部的资源有限环境中接受多模式治疗的非转移性癌食管患者的真实世界数据作者：Ravi Teja R.Matta（印第安纳州拉贾蒙德里） 192P-探索氯硝柳胺在食管鳞状细胞癌中对EHMT2的调节作用作者：I-Chen Wu（台湾高雄市） 193P-DCLK1的激酶活性驱动其在食管鳞状细胞癌中的促干性作用作者：Yuping Yang（中国福州） 194P-呋喹替尼联合S-1治疗一线免疫治疗失败后ESCC患者的剂量探索结果更新作者：Ningning Li（中国北京） 195P-miR-10a-5p靶向TFAP2C促进食管癌的顺铂耐药作者：Kiran Pasbola（印第安纳州新德里） 196P-可切除胃和胃食管结合部癌的围手术期FLOT+免疫治疗的系统评价和荟萃分析作者：Lorenz Fort E.Revillas（奎松市，菲律宾） 198P-新辅助多西他赛加顺铂、5-FU治疗可切除局部晚期食管鳞状细胞癌后，辅助纳武利尤单抗治疗的疗效和安全性作者：Nozomu Ogura（日本） 244P-基因组分析检测对胃肠道神经内分泌癌治疗结果的影响作者：Toshiki Ozato（日本冈山） 263TiP-TroFuse-015：TROP2定向抗体-药物偶联物sac-TMT对比医生选择的方案治疗经治转移性胃食管腺癌的Ⅲ期研究作者：Kohei Shitara（日本） 264TiP-一项评估德曲妥珠单抗（trastuzumab deruxtecan，T-DXd）联合rilvegostomig和化疗治疗HER2阳性（HER2+）和HER2低表达的胃或胃食管结合部腺癌（GEJA）患者的Ⅰb/Ⅱ期开放标签研究：DESTINY-Gastric03研究第4部分作者：Yelena Y.Janjigian（美国纽约） 265TiP-Ⅰ/Ⅱ期开放标签、伞式平台设计的研究药物联合或不联合pembrolizumab和/或化疗对既往接受过PD-（L）1抑制剂治疗的晚期食管癌患者的研究：KEYMAKER-U06子研究作者：Sean Kato（日本） 266TiP-替雷利珠单抗联合S-1对于新辅助免疫化疗后根治性切除术后残留原发病灶和淋巴结阴性食管鳞状细胞癌患者的疗效：一项Ⅱ期多中心试验（PPIO-008）作者：Yingjian Wang（中国重庆） 267TiP-CHAPTER-GIST-101：pimitespib联合伊马替尼治疗伊马替尼难治性胃肠道间质瘤患者的Ⅰ期研究作者：WeiPeng Yong（新加坡）胰腺癌 250P-评估液体活检衍生的循环肿瘤DNA（ctDNA）作为预测生物标志物对早期胰腺癌治疗反应的影响作者：Hashim Talib Hashim（Karbala） 252P-XELOXIRI方案在不可切除胰腺导管腺癌患者中的安全性和有效性作者：Biyang Cao（中国北京） 253P-预后营养指数是接受新辅助化疗和手术切除的胰腺癌患者继续S-1辅助化疗的独立危险因素作者：Shinnosuke Kawahara（日本横滨） 255P-NALLONG研究的亚洲队列中既往接受过脂质体伊立替康治疗的转移性胰腺导管腺癌长期幸存者的真实世界结果作者：Chang hoon Yoo（韩国首尔） 256P-胰腺导管腺癌中的PIK3CA突变作者：Omali Pitiyarachchi（澳大利亚兰德威克） 257P-“H”至“H”精准新辅助化疗可提高胰腺癌的可切除率作者：Yonggang He（中国重庆） 258P-真实世界背景下晚期胰腺癌患者治疗方案和总生存期的当前趋势作者：Hiroshi Imaoka（日本） 259P-伊立替康脂质体为基础的方案在中国晚期胰腺癌患者中的应用：一项前瞻性、多中心、观察性真实世界研究作者：Jin Xu（中国上海） 260P-NALIRIFOX作为基于吉西他滨的化疗后转移性胰腺癌的后续治疗：单中心真实世界经验作者：Hisn-Chen Lin（台湾嘉义市）（来源：肿瘤瞭望消化时讯）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床2期放射疗法

2024-10-30

·新药前沿

周围神经痛新靶点药物开发复苏

随着人口老龄化，以糖尿病性周围神经病理性疼痛（DPNP）、带状疱疹后神经痛（PHN）为代表的周围神经病理性疼痛（pNP）的发病率逐年增加。与此同时，过去20年对疼痛和痛觉的神经生物学研究也不断取得积极的进展，生物制药行业在探索不同机制pNP新药开发方面初见成效。尽管已获批上市超过20年，加巴喷丁、普瑞巴林仍旧是周围神经病理性疼痛临床治疗的金标准。普瑞巴林作为第二代钙离子通道调节剂，与加巴喷丁相比，增强了与α2-δ 亚基的亲和力，滴定和起效更快，但仍旧不可避免嗜睡、头晕、周围性水肿、视物模糊等不良反应的发生。第三代钙离子通道调节剂，通过提高对中枢神经系统α2δ亚基靶点亲和力，可进而提高疗效和降低不良反应发生率。2款第三代钙离子通道调节剂近年相续获得批准上市：第一三共开发的Tarlige（Mirogabalin/美洛加巴林）2019年1月首次在日本获批上市用于神经性疼痛治疗。2024年6月在我国获批进口上市用于DPNP（商品名德力静）。美洛加巴林对钙离子通道α2δ亚基具有较高的亲和力，且其与α2δ-1亚基解离缓慢，与α2δ-2亚基解离快速，该机制可能是其具有较好的镇痛治疗效果和较少不良反应的原因。海思科开发的思美宁（Crisugabalin/克利加巴林）于2024年5月在我国获批上市用于DPNP，并随后于7月获批PHN，克利加巴林（HSK16149 ）抑制[ 3H ]加巴喷丁与α2δ的结合亚单位与美洛加巴林相当，作用比普瑞巴林强23倍。克利加巴林是全球首个无需滴定的第三代中枢神经系统钙离子通道调节剂，也是国内首个获批DPNP适应症的药物。随着第三代钙离子通道调节剂在国内获批上市，我国DPNP临床治疗也正在迎来新格局。 2024年5月，我国发布的《国家基层糖尿病神经病变诊治指南（2024版）》就建议，对于DPNP，普瑞巴林或度洛西汀可作为首选，加巴喷丁、美洛加巴林、克利加巴林也可作为一种有效的初始治疗药物。衔接蛋白2相关激酶1（AAK1）是丝氨酸/苏氨酸激酶Ark1/Prk1家族成员，在调节受体内吞作用中发挥作用。 AAK1被确定为治疗神经性疼痛的潜在治疗靶点是基于2016年的一项研究结果：AAK1基因敲除（KO）小鼠对小鼠福尔马林模型的急性疼痛期（I期）反应正常，但对持续疼痛期（II期）反应减弱。AAK1基因敲除小鼠在脊神经结扎（SNL）手术后也没有出现触觉异常性疼痛。 AAK1抑制剂治疗神经性疼痛的机制（行为和电生理学）与α2肾上腺素能信号传导有关，α2肾上腺素能信号传导是人类已知的抗伤害性通路。 Lexicon与百时美施贵宝（BMS）合作开发的AAK1抑制剂LX9211（BMS-986176）具有治疗DPNP、PHN和神经性疼痛潜力。 2023年6月，LX9211治疗DPNP的疗效和安全性IIa期概念验证研究（RELIEF-DPN1）结果发表在《糖尿病护理》杂志：对于中度至重度DPNP患者，低剂量LX9211治疗6周后，与安慰剂相比，达到了主要疗效终点。虽然高剂量LX9211的结果也表明疼痛在数值上有所减轻，但并未达到预先规定的显著性水平，这可能是因为高剂量组TEAE发生率较高，导致治疗中断有关。尽管两种剂量的LX9211发生TEAE的几率都高于安慰剂，但低剂量LX9211组总体上耐受性良好。尽管II期概念验证研究存在治疗时间相对较短和仅在美国招募参与者限制，但主要疗效终点得到满足，支持将AAK1转化为治疗神经病理性疼痛的新型治疗靶点，如在动物模型中观察到的，使用AAKI抑制剂LX9211可缓解神经病理性疼痛。基于概念验证研究结果而正在开展的剂量范围探索IIb期PROGRESS试验预计于2025年第二季度公布结果。与此同时，Lexicon与百时美施贵宝也正在筹划LX9211治疗DPN推进到Ⅲ期临床试验。 LX9211的IIa期概念验证研究成功开始引起国内多家公司fast-follow布局，包括海思科、人福、扬子江药业旗下的上海海雁等。海思科开发的HSK36357用于周围神经病理性疼痛I期试验于今年5月结束，上海海雁的YZJ-1495盐酸盐胶囊正在进行神经病理性疼痛I期试验。尽管尚未公布研发项目信息，推测可能是AAK1抑制剂。 2022年1月，Biohaven公司（该公司已于2022年10月被辉瑞收购）与比利时天主教鲁汶大学（KU Leuven）药物设计和发现中心（CD3）与离子通道研究实验室（LICR）宣布，签署独家全球许可和研究协议，开发和商业化first-in-class的TRPM3拮抗剂，以解决全球越来越多的慢性疼痛患者问题。BHV-2100是基于天主教鲁汶大学研究平台开发的一种口服小分子TRPM3拮抗剂。 TRPM3是天主教鲁汶大学LICR发现的治疗疼痛的新靶点。 TRPM3是一种参与疼痛信号传导的Ca2+通透性非选择性阳离子通道，在背根神经节（DRG）和三叉神经节的痛觉神经元中高度表达，在疼痛感知中起关键作用，可能是内源性疼痛缓解途径的下游靶点。动物实验数据表明TRPM3在神经性疼痛的自发性疼痛和热痛觉过敏中发挥作用，而且位于脊髓、中枢突起或DRG神经元细胞体中的TRPM3在调节热敏感性方面也发挥着重要作用。与TRPM3在疼痛中的作用一致，天主教鲁汶大学的研究数据表明，BHV-2100可以减轻动物模型中的疼痛行为，而不会产生其他疼痛疗法和机制所见的严重不良反应。 2024年5月，Biohaven在公司2024年投资者研发日活动介绍了已完成的BHV-2100的I期研究药代动力学和安全性数据。结果表明，该药物吸收迅速，20分钟内即可达到治疗浓度。单剂量高达500mg时，耐受性良好，超过了预期的治疗剂量，远高于EC90浓度。这些发现为BHV-2100进入临床试验提供了有力的证据支持，可用于治疗急性偏头痛和疼痛，是一种对中枢神经系统副作用非常小的非阿片类药物疗法。 Biohaven计划于2024年下半年启动偏头痛急性治疗的II期研究和疼痛的概念验证研究（POC）。Biohaven也在筹备提交BHV-2100用于慢性疼痛IND 计划。在国内，深圳晶蛋生物医药已开始进行TRPM3靶点的抗体专利布局。热休克蛋白90（HSP90）是一种普遍存在的信号转导调节剂，Hsp90抑制剂作为癌症治疗药物已获得临床成功（全球首款HSP90抑制剂Jeselhy已于2022年在日本获批上市用于治疗癌症化疗后进展的胃肠道间质瘤）。然而，Reata Pharmaceuticals公司（该公司已于2023年9月被渤健收购）尝试把Hsp90抑制剂推进到疼痛领域。 Reata Pharmaceuticals开发（从堪萨斯大学获得授权）的Cemdomespib（RTA901）是一种高效、选择性口服小分子Hsp90 C端调节剂。Cemdomespib可与Hsp90的C端结合，从而增加细胞保护基因和分子伴侣基因（包括Hsp70）的转录和 Hsp70蛋白的表达。调节HSP90和诱导HSP70有可能减轻糖尿病神经痛。在过去十年中，大量研究证据表明，通过诱导Hsp70可改善糖尿病周围神经病变和快速发作的脱髓鞘性神经病变。Cemdomespib是一种进入临床研究的第二代新型药物，在人体研究中表现出了良好的药代动力学和安全性。Cemdomespib具有改善病因与蛋白聚集无关的周围神经病方面的疗效。 Cemdomespib对DNDP患者的安全性和有效性的II期研究目前正在研究中。内容来源于网络，如有侵权，请联系删除。

上市批准

2023-05-10

·PRNewswire

Soft Tissue Sarcoma Pipeline Space Brims With Novel Emerging Therapies with Over 125 Key Companies Working in the Domain | DelveInsight

The prevalence of soft tissue sarcoma has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of soft tissue sarcoma and the growing research and development activities to develop novel therapies to treat soft tissue sarcoma to drive the market. The companies developing the potential therapies in the last stage of development include Advenchen Laboratories, Philogen, Nanobiotix, and several others. LAS VEGAS, May 10, 2023 /PRNewswire/ -- DelveInsight's ' Soft Tissue Sarcoma Pipeline Insight – 2023 ' report provides comprehensive global coverage of available, marketed, and pipeline soft tissue sarcoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the soft tissue sarcoma pipeline domain. Key Takeaways from the Soft Tissue Sarcoma Pipeline Report DelveInsight's soft tissue sarcoma pipeline report depicts a robust space with 125+ active players working to develop 130+ pipeline therapies for soft tissue sarcoma treatment. Key soft tissue sarcoma companies such as Advenchen Laboratories, Philogen, Gradalis, Epizyme, Chugai Pharma France, CytRx, Taiho Pharmaceuticals, KaryoPharm Therapeutics, Nanobiotix, Apexigen, Lytix Biopharma, Incyte Corporation, Iovance Biotherapeutics, Aadi Bioscience, Inc., AVEO Pharmaceuticals, Bayer, VasGene Therapeutics, Mirati Therapeutics, Novartis Pharmaceuticals, Incyte Corporation, Tracon Pharmaceuticals, Jiangsu Hengrui Medicine, Exelixis, Qbiotics, AstraZeneca, Loxo Oncology, ImmunityBio, Monopar Therapeutics, Chipscreen Biosciences, Ltd., Agenus, C4 Therapeutics, Inc., Noxopharm Limited, Moleculin Biotech, Inc., Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., Tracon Pharmaceuticals Inc., Guangdong Xiangxue Precision Medical Technology Co., Ltd., Cornerstone Pharmaceuticals, Takara Bio Inc., Jazz Pharmaceuticals, Lyell Immunopharma, Telix Pharmaceuticals, and others are evaluating new soft tissue sarcoma drugs to improve the treatment landscape. Promising soft tissue sarcoma pipeline therapies in various stages of development include AL-3818, Onfekafusp alfa, Vigil, Tazemetostat, Aldoxorubicin, TAS-116, Selinexor, NBTXR3, APX005M, GPX-150, LTX-315, Lenvatinib, Chiauranib, Zalifrelimab, INCB081776, LN-145-S1, ABI-009, Tivozanib, LOXO-101, sEphB4-HSA, Sitravatinib, Envafolimab, Camrelizumab, Tigilanol Tiglate, Durvalumab, Tremelimumab, CFT8634, NOX66, Liposomal Annamycin, 609A, YH001, TAEST16001, CPI-613+Hydroxychloroquine, TBI-1301, Lurbinectedin, LYL132, and others. In October 2022, LIXTE Biotechnology Holdings, Inc. announced that the Spanish Agency for Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) had authorized a Phase 1b/randomized Phase 2 study of LB-100, the Company's lead clinical compound, plus doxorubicin versus doxorubicin alone, the global standard for initial treatment of advanced soft tissue sarcomas (ASTS). In September 2022, Immutep Limited was pleased to announce it has signed a Material Transfer Agreement ("Agreement") with the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, to enable an investigator-initiated open-label Phase II clinical trial. The trial will evaluate Immutep's lead product candidate, efti in combination with pembrolizumab and radiotherapy in the neoadjuvant setting (prior to surgery) in up to 40 patients with select soft tissue sarcoma (STS). In September 2022, TRACON Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted fast-track designation for the development of envafolimab (KN035) for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy. In September 2022, Avacta Group plc announced that the US Food and Drug Administration (FDA) had granted Orphan Drug Designation (ODD) to the company's lead pre|CISION drug candidate, AVA6000, for treatment of soft tissue sarcoma.AVA6000 is a form of the generic chemotherapy doxorubicin that has been modified using the pre|CISION technology so that it is activated predominantly in the tumor with the aim of sparing healthy tissue from exposure and improving the safety, tolerability, and efficacy of the drug. In May 2022, Immix Biopharma, Inc., announced positive interim study data showing that after one cycle of treatment, ImmixBio's lead candidate IMX-110 produced 75% survival vs. 0% survival for Trabectedin (sold as YONDELIS ® by Janssen, a Johnson & Johnson Company, a U.S. FDA approved drug) in a connective tissue cancer Soft Tissue Sarcoma (STS) mice study. In this study, IMX-110 was compared against approved drugs used to treat STS. Trabectedin was dosed according to Meco et al., 2003 (trabectedin monotherapy treatment arm), and IMX-110 was administered at 2.0 mg/kg. In April 2022, Telix Pharmaceuticals Limited announced that it has entered into a license agreement with Eli Lilly and Company ("Lilly") under which Telix is granted exclusive worldwide rights to develop and commercialize radiolabelled forms of Lilly's olaratumab antibody for the diagnosis and treatment of human cancers. Telix's initial development focus will be on a rare type of cancer known as soft tissue sarcoma (STS). Request a sample and discover the recent advances in soft tissue sarcoma drug treatment @ Soft Tissue Sarcoma Pipeline Report The soft tissue sarcoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage soft tissue sarcoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the soft tissue sarcoma clinical trial landscape. Soft Tissue Sarcoma Overview Soft-tissue sarcomas (STS) are rare neoplasms that can develop in supporting or connective tissue, such as muscle, nerves, tendons, blood vessels, and fatty and fibrous tissues. They commonly affect the arms, legs, and trunk. They can also be found in the stomach and intestines (GIST), behind the abdomen (retroperitoneal sarcomas), and in the female reproductive system (gynecological sarcomas). Soft tissue sarcomas are classified based on the cell type involved, the nature of the malignancy, and the clinical course of the disease. The signs and soft tissue sarcoma symptoms differ greatly between patients depending on the type of soft tissue sarcoma. It is not associated with any obvious symptoms early in the course of the disease, but affected individuals may notice a slow-growing, painless mass in the affected area. Find out more about drugs for soft tissue sarcoma @ New Soft Tissue Sarcoma Drugs A snapshot of the Soft Tissue Sarcoma Pipeline Drugs mentioned in the report: Learn more about the emerging soft tissue sarcoma pipeline therapies @ Soft Tissue Sarcoma Clinical Trials Soft Tissue Sarcoma Therapeutics Assessment The soft tissue sarcoma pipeline report proffers an integral view of soft tissue sarcoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Soft Tissue Sarcoma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Infusion, Intra-arterial, Intradermal, Intralesional, Intratumoral, Intravenous, Oral, Parenteral, Subcutaneous Therapeutics Assessment By Molecule Type: Antibody, Antibody-drug conjugate, Cell therapy, Gene therapy, Immunotherapy, Nanoparticle, Peptide, Recombinant fusion protein, Small molecule Therapeutics Assessment By Mechanism of Action: Fibroblast growth factor receptor antagonists, Platelet-derived growth factor beta receptor antagonists, Proto oncogene protein c-kit inhibitors, Vascular endothelial growth factor receptor 3 antagonists, Vascular endothelial growth factor receptor-1 antagonists, Vascular endothelial growth factor receptor-2 antagonists, Immunostimulants, Free radical stimulants, DNA intercalators, Type II DNA topoisomerase inhibitors, Cell membrane structure modulators, Antibody-dependent cell cytotoxicity, Programmed cell death-1 receptor antagonists, T lymphocyte stimulants, Type 1 fibroblast growth factor receptor antagonists, Type 3 fibroblast growth factor receptor antagonists, Type 4 fibroblast growth factor receptor antagonists, Type-2 fibroblast growth factor receptor antagonists, Fms-like tyrosine kinase 3 inhibitors, Lymphocyte specific protein tyrosine kinase p56(lck) inhibitors; Lyn protein-tyrosine kinase inhibitors, Src-Family kinase inhibitors Key Soft Tissue Sarcoma Companies: Advenchen Laboratories, Philogen, Gradalis, Epizyme, Chugai Pharma France, CytRx, Taiho Pharmaceuticals, KaryoPharm Therapeutics, Nanobiotix, Apexigen, Lytix Biopharma, Incyte Corporation, Iovance Biotherapeutics, Aadi Bioscience, Inc., AVEO Pharmaceuticals, Bayer, VasGene Therapeutics, Mirati Therapeutics, Novartis Pharmaceuticals, Incyte Corporation, Tracon Pharmaceuticals, Jiangsu Hengrui Medicine, Exelixis, Qbiotics, AstraZeneca, Loxo Oncology, ImmunityBio, Monopar Therapeutics, Chipscreen Biosciences, Ltd., Agenus, C4 Therapeutics, Inc., Noxopharm Limited, Moleculin Biotech, Inc., Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd., Tracon Pharmaceuticals Inc., Guangdong Xiangxue Precision Medical Technology Co., Ltd., Cornerstone Pharmaceuticals, Takara Bio Inc., Jazz Pharmaceuticals, Lyell Immunopharma, Telix Pharmaceuticals, and others. Key Soft Tissue Sarcoma Pipeline Therapies: AL-3818, Onfekafusp alfa, Vigil, Tazemetostat, Aldoxorubicin, TAS-116, Selinexor, NBTXR3, APX005M, GPX-150, LTX-315, Lenvatinib, Chiauranib, Zalifrelimab, INCB081776, LN-145-S1, ABI-009, Tivozanib, LOXO-101, sEphB4-HSA, Sitravatinib, Envafolimab, Camrelizumab, Tigilanol Tiglate, Durvalumab, Tremelimumab, CFT8634, NOX66, Liposomal Annamycin, 609A, YH001, TAEST16001, CPI-613+Hydroxychloroquine, TBI-1301, Lurbinectedin, LYL132, and others. Dive deep into rich insights for new drugs for soft tissue sarcoma treatment; visit @ Soft Tissue Sarcoma Medications Table of Contents For further information on the soft tissue sarcoma pipeline therapeutics, reach out @ Soft Tissue Sarcoma Drug Treatment Related Reports Soft Tissue Sarcoma Market Soft Tissue Sarcoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key soft tissue sarcoma companies, including Gem Pharmaceuticals, Lytix Biopharma, Incyte Corporation, Daiichi Sankyo, NantPharma, Iovance Biotherapeutics, Agenus, Eli Lilly and Company, Adaptimmune, Aadi, AVEO Pharmaceuticals, Amgen, among others. Soft Tissue Sarcoma Epidemiology Forecast Soft Tissue Sarcoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the soft tissue sarcoma epidemiology trends. Clear Cell Sarcoma Pipeline Clear Cell Sarcoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products and the key clear cell sarcoma companies, including Tesaro, NantPharma, Rafael Pharmaceuticals, Pfizer, among others. Ewing Sarcoma Pipeline Ewing Sarcoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key Ewing sarcoma companies, including Gradalis, Inc., Shanghai Pharmaceuticals Holding Co., Ltd, Tyme, Inc, Pfizer, Hutchison Medipharma Limited, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

引进/卖出孤儿药快速通道临床2期

100 项与 Pimitespib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14876

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
胃肠道间质瘤	日本	Taiho Pharmaceutical Co., Ltd.	2022-06-20

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10 条进展最快的记录,

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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1期	美国	Taiho Oncology, Inc.	2017-07-10
晚期恶性实体瘤	临床1期	意大利	Taiho Oncology, Inc.	2017-07-10
晚期恶性实体瘤	临床1期	英国	Taiho Oncology, Inc.	2017-07-10

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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


NCT05245968 (CHAPTER-GIST-101, ESMO2023) 人工标引	临床1期	胃肠道间质瘤二线	12	Pimitespib + Imatinib	齋鬱鏇製艱構膚鹽觸遞(鹹製艱窪範鑰淵淵繭夢) = 憲廠積獵顧糧窪淵醖廠糧鹹願網鏇製鹹艱繭遞 (廠襯艱願觸繭廠製憲構 ) 更多	积极	2023-10-21
ERS2022	N/A	肺纤维化 HSP90	-	TAS-116	繭醖觸壓築構憲廠艱鏇(蓋遞繭廠遞製鑰蓋淵餘) = Mice treated with TAS-116, starting either 24h or 96h after HCl exposure, demonstrated downregulation of TGFβ signaling 觸製蓋簾構選鬱網獵鬱 (簾壓選廠遞齋廠構網積 ) 更多	-	2022-09-04
JPRN-JapicCTI-184094 (ASCO2021)	临床3期	胃肠道间质瘤	86	Pimitespib 160 mg	憲憲鑰範鏇觸鹹艱膚壓(糧壓製糧壓齋繭簾鏇選) = 衊壓範憲淵醖簾獵觸餘選憲鏇鏇夢鏇蓋齋憲壓 (鹹鏇憲鬱膚觸獵憲鬱鑰, 9.2–not reached) 更多	积极	2021-05-28
JPRN-JapicCTI-184094 (ASCO2021)	临床3期	胃肠道间质瘤	86	Placebo	憲憲鑰範鏇觸鹹艱膚壓(糧壓製糧壓齋繭簾鏇選) = 獵壓顧繭構觸顧蓋蓋襯選憲鏇鏇夢鏇蓋齋憲壓 (鹹鏇憲鬱膚觸獵憲鬱鑰, 5.5–not reached) 更多	积极	2021-05-28
JPRN-UMIN000032801 (EPOC1704, ASCO2020)	临床1期	实体瘤 \| 结直肠癌	44	TAS-116 plus nivolumab	憲壓構廠壓網醖鑰顧鑰(膚糧願鹹築積壓壓襯獵) = 鹽鹽膚艱積鑰構鑰齋範壓繭顧壓獵選積糧憲糧 (獵構願網構網鏇衊鑰觸 ) 更多	积极	2020-05-25
NCT02965885 (ASCO2017) 人工标引	临床1期	晚期恶性实体瘤	52	Pimitespib	淵願繭簾築蓋製蓋膚窪(膚膚願鑰鹽廠選顧構醖) = gastrointestinal disorders and increased creatinine 製願積鑰簾範淵鏇築窪 (襯網艱築獵製構壓醖範 )	积极	2017-06-05
NCT02965885 (ASCO2017) 人工标引	临床1期	晚期恶性实体瘤	52	Pimitespib (QD)		积极	2017-06-05