A Randomized, Double-Blind, Two Treatment, Two Period, Chronic Dosing (2 Weeks), Cross-Over, Multi-Center Study to Evaluate the Effects of PT001 and PT005 on Specific Image Based Airway Volumes and Resistance in Subjects With Moderate to Severe COPD.

开始日期2016-10-31

申办/合作机构

Pearl Therapeutics, Inc.

JPRN-JapicCTI-184077 / Unknown status临床3期

A Randomized, Double-Blind, Chronic Dosing (24 Weeks), Placebo-Controlled, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo (PT003014)

开始日期-

申办/合作机构

Pearl Therapeutics, Inc.

100 项与 PT001 相关的临床结果

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100 项与 PT001 相关的转化医学

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100 项与 PT001 相关的专利（医药）

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项与 PT001 相关的文献（医药）

2024-09-12·ACS Medicinal Chemistry Letters

Analysis of Antiangiogenic Potential and Cell Death Mechanism of a Kinetically Inert Platinum Antitumor Agent

Article

作者: Patra, Malay ; Dey, Saurabh ; Panda, Tushar Ranjan ; Ray, Pritha ; M, Manikandan ; Chhatar, Sushanta ; Chakraborty, Sourav ; Patra, Chinmoy

Cancer is a multifaceted disease involving various pathological processes, including uncontrolled proliferation, development of resistance, angiogenesis, metastasis, etc. Therefore, chemotherapeutic agents capable of simultaneously inhibiting proliferation, circumventing chemoresistance, and inhibiting angiogenesis can address multiple aspects of cancer progression. We recently identified a highly promising kinetically inert platinum antitumor agent, namely, Pt-1, that can circumvent cisplatin resistance and showed negligible nephrotoxicity. In this study, we explored the antiangiogenic potential and elucidated the detailed mechanism of cell death through which it exerts its antitumor activity. Pt-1 strongly inhibited angiogenesis in a zebrafish in vivo model at its therapeutically relevant nontoxic dose. Further, Pt-1 exerted antitumor activity through necroptosis- and paraptosis-mediated cell death. Taken together, the combination of antitumor activity with antiangiogenic property in Pt-1 makes it a highly promising antitumor candidate.

2024-02-12·Angewandte Chemie (International ed. in English)

Narrowband Near‐Infrared Multiple‐Resonance Thermally Activated Delayed Fluorescence Emitters towards High‐Performance and Stable Organic Light‐Emitting Diodes

Article

作者: Hua, Tao ; Huang, Zhongyan ; Yang, Chuluo ; Miao, Jingsheng ; Cao, Xiaosong ; Wang, Xinzhong ; Zhang, Youming ; Wang, Lian ; Li, Nengquan ; Chen, Zhanxiang

Abstract:

Multiple‐resonance thermally activated delayed fluorescence (MR‐TADF) materials are highly coveted for their high efficiency and narrowband emission in organic light‐emitting diodes (OLEDs). Nevertheless, the development of near‐infrared (NIR) MR‐TADF emitters remains a formidable challenge. In this study, we design two new NIR MR‐TADF emitters, PXZ−R−BN and BCz−R−BN, by embedding 10H‐phenoxazine (PXZ) and 7H‐dibenzo[c,g]carbazole (BCz) fragments to increase the electron‐donating ability or extending π‐conjugation on the framework of para‐boron fusing polycyclic aromatic hydrocarbons (PAHs). Both compounds emit in the NIR region, with a full‐width at half‐maximum (FWHM) of 49 nm (0.13 eV) for PXZ−R−BN and 43 nm (0.11 eV) for BCz−R−BN in toluene. To sensitize the two NIR MR‐TADF emitters in OLEDs, a new platinum complex, Pt‐1, is designed as a sensitizer. The PXZ−R−BN‐based sensitized OLEDs achieve a maximum external quantum efficiency (EQEmax) of nearly 30 % with an emission band at 693 nm, and exceptional long operational stability with an LT97 (time to 97 % of the initial luminance) value of 39084 h at an initial radiance of 1000 mW sr−1 m−2. The BCz−R−BN‐based OLEDs reach EQEmax values of 24.2 % with an emission band at 713 nm, which sets a record value for NIR OLEDs with emission bands beyond 700 nm.

2022-12-01·Journal of nanobiotechnology

Light triggered release of a triple action porphyrin-cisplatin conjugate evokes stronger immunogenic cell death for chemotherapy, photodynamic therapy and cancer immunotherapy

Article

作者: Xiao, Haihua ; Li, Juyi ; Cai, Zhenghao ; Qi, Ruogu ; Song, Haiqin ; Zheng, Minhua

Abstract:

Photodynamic therapy (PDT) has emerged as an attractive therapeutic approach which can elicit immunogenic cell death (ICD). However, current ICD inducers are still very limited as the representative ICD induces of photosensitizers can only evoke insufficient ICD to achieve unsatisfactory cancer immunotherapy. Herein, we demonstrated the use of a triple action cationic porphyrin-cisplatin conjugate (Pt-1) for drug delivery by a reactive oxygen species (ROS) sensitive polymer as nanoparticles (NP@Pt-1) for combined chemotherapy, PDT and immunotherapy. This unique triple action Pt-1 contains both chemotherapeutic Pt drugs and Porphyrin as a photosensitizer to generate ROS for PDT. Moreover, the ROS generated by Pt-1 can on the one hand degrade polymer carriers to release Pt-1 for chemotherapy and PDT. On the other hand, the ROS generated by Pt-1 subsequently triggered the ICD cascade for immunotherapy. Taken together, we demonstrated that NP@Pt-1 were the most effective and worked in a triple way. This study could provide us with new insight into the development of nanomedicine for chemotherapy, PDT as well as cancer immunotherapy.

项与 PT001 相关的新闻（医药）

2023-05-27

·生物制药小编

硬币的另一面：PD-1激动剂来了

对于PD-1这个靶点，想必大家都不陌生。过去十年来，PD-1带来的惊喜已经远远超过其他靶点。PD-1作为抑制剂用于肿瘤的免疫治疗大放异彩，但在自免领域其潜力并未完全发掘。其实早在20年前，就有药企开始用PD-1来治疗自身免疫疾病的这个思路开始研发。机缘巧合、鬼使神差之下，PD-1 激动剂没研发成，反而意外获得了一款PD-1抑制剂。这也是第一款PD-1抑制剂O药的前身。大幅领先的礼来上周，礼来的在研PD-1激动剂获得了新的进展，同时也验证了PD-1作为激动剂的可行性。其PD-1激动剂peresolimab治疗难治性类风湿关节炎（RA）的2a期研究的详细结果，试验达到了主要疗效终点。在这项随机、双盲、安慰剂对照的IIa期临床研究中，98例患有活动性中重度类风湿性关节炎且对改善病情抗风湿药（DMARDs）应答不足的受试者以2:1:1随机接受每4周1次 700mg peresolimab（n=49）、300mg peresolimab（n=25）或安慰剂（n=24）。试验主要终点为基于 C 反应蛋白水平的 28 个关节疾病活动评分（DAS28-CRP）从基线至第 12 周的变化，主要比较 700 mg 组与安慰剂组之间的差异；次要终点则包括较基线实现 20%、50%、70% 缓解（即 ACR20、50、70）的患者比例等指标。结果显示，与安慰剂相比，第12周，每4周静脉注射1次peresolimab 700mg剂量组DAS28-CRP评分较基线变化值显著高于安慰剂组（P<0.001）。次要终点方面，700mg 组 ACR20 应答优于安慰剂。安全性方面，peresolimab 耐受性良好，治疗组与安慰剂组副作用发生率相当。此次2期临床试验成功验证了PD-1激动剂所具备的潜力。礼来也表示 peresolimab 会在风湿性疾病中的进一步开发，同时也将考虑将该药应用于其他自身免疫疾病。不过对于礼来的PD-1激动剂成功同样收到了反对的声音。《新英格兰医学杂志》的一篇文章讨论了关于礼来的PD-1激动剂可能存在的潜在问题，文章提到：“因为PD-1激动剂这种治疗方法不是抗原特异性的，所以有可能造成癌症的发展，并且这种风险可能在短时间内无法确定。”其他追赶者在PD-1激动剂这一领域中追赶礼来最紧的是Anaptys Bio公司。Anaptys Bio公司开发的rosnilimab（曾用名ANB030）是一种PD-1激动剂单克隆抗体，用于治疗斑秃。目前该药物已经启动了一项随治疗中度至重度斑秃的2期试验，预计在今年下半年获得临床结果。除此之外Anaptys Bio还有一款PD-1激动剂资产CC-90006，最初与新基合作，但百时美施贵宝收购新基后似乎在1期临床后停止了这条管线。默沙东在PD-1激动剂上也拥有两条管线。此前默沙东以19亿美元收购了Pandion，后者带来了PD-1激动剂PT627和PT001。前者具有全身活性，而后者携带MAdCAM，用于肠道和肝脏靶向。尽管默沙东对Pandion的资产没有透露太多，但它已将PT101(现在称为MK-6194)推进至1期临床阶段。另外，去年8月，吉利德(Gilead)以4.05亿美元收购Microbio，收购了MB151，获得了PD-1激动剂。而Ibio以100万美元收购Rubryc，获得了RTX-002的权利;两款PD-1激动剂都处于临床前阶段。在国内，PD-1激动剂的市场仍处于相对空白地带，研发的企业较少，目前仅明治医药拥有一条相应管线。天境生物则拥有一条PD-L1激动剂管线，针对类风湿关节炎与红斑狼疮。两款药物同样处于临床前阶段。小结现如今，有着巨大容量的自免市场，PD-1同样蕴藏着巨大机会。礼来、默沙东等海外药企纷纷在激动剂上投入，研发用于自身免疫治疗的PD-1激动剂。PD-1激动剂的不断推进，或许未来不久，我们就能见到PD-1激动剂能够有效应用于类风湿性关节炎、银屑病、系统性红斑狼疮等自免疾病。参考资料：1.https://mp.weixin.qq.com/s/9Na92pafT_jZ7AKk7Vi5jQ

临床2期免疫疗法并购临床失败临床3期

2023-05-02

·Outsourcing Pharma

VeriSIM partners with Clarivate for early-stage drug development

VeriSIM Life, a developer of AI tools for drug development, partnered with Clarivate, an information services company, to provide pharma and biotech companies with R&D insights through their solutions. According to the companies, they will offer tools that are able to de-risk and accelerate drug discovery, as well as helping to avoid late-stage failures during clinical trials. The two solutions that will be combined are VeriSIM’s BIOiSIM platform, and Clarivate’s Cortellis Drug Discovery Intelligence. Clarivate’s tool provides preclinical drug intelligence, which involves access to a research database that has been manually curated, validated, and shared by scientists. Access to the database delivers companies data on pipelines, patents, literature, and conferences. In addition, it can be used to identify, validate and prioritize targets and biomarkers, as well as giving information on metabolic pathways and potential toxicity events. VeriSIM describes its own platform as a ‘virtual drug development engine’ that uses AI and machine learning to make early predictions about compound safety and efficacy. The solution also features a ‘Translational Index’ technology that is used to determine whether the strongest drug candidate to progress from a selection of options. The company also offers to partner with organizations to co-develop new drugs using the platform to determine the most likely drug candidate to succeed, with VeriSIM noting that this can shorten development time. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Gavin Coney, VP of partnerships at Clarivate, said, “Working with the combination of Clarivate and VeriSIM Life will allow companies to benefit by gaining additional and valuable insights that can reduce risk, provide them with information to make more informed decisions with extraordinary accuracy, and bridge the translational gap between pre-clinical and clinical research. Ultimately, this partnership can bring life-saving treatments to patients more quickly.” VeriSIM also owns a pharmaceutical subsidiary in the form of PulsoSIM Therapeutics. This company has been set up to target pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF), using BIOiSIM to deliver its preclinical pipeline. PulsoSIM has two assets in its pipeline, one for each of the mentioned conditions. PT001, which is currently in late preclinical studies for PAH, and PT002 for IPF, which is going through in-vitro studies. The company was launched in 2021, and shortly after in June 2021, PT001 was granted orphan drug designation by the US Food and Drug Administration.

孤儿药

100 项与 PT001 相关的药物交易

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