DO-2(DO-2) - 药物靶点：c-Met_在研适应症：肺癌，晚期恶性实体瘤，非小细胞肺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

DO 2、DO2

靶点

c-Met

作用机制

c-Met抑制剂(肝细胞生长因子受体抑制剂)

治疗领域

肿瘤呼吸系统疾病

在研适应症

肺癌晚期恶性实体瘤非小细胞肺癌+ [2]

非在研适应症-

原研机构

DeuterOncology SA初创企业

在研机构

DeuterOncology SA初创企业

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

2

项与 DO-2 相关的临床试验

CTIS2023-504897-39-00 / Recruiting

- DO2.22.01

开始日期2023-04-13

申办/合作机构

DeuterOncology SA初创企业

[+1]

CTIS2024-518581-27-00 / Not yet recruiting

A Study to evaluate the effect of a high-fat meal on the Pharmacokinetics of the Selective MET kinase Inhibitor DO-2 in subjects in good health

开始日期-

申办/合作机构

DeuterOncology SA初创企业

100 项与 DO-2 相关的临床结果

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100 项与 DO-2 相关的转化医学

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100 项与 DO-2 相关的专利（医药）

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14

项与 DO-2 相关的文献（医药）

2022-02-18·European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery2区 · 医学

Critical oxygen delivery threshold during cardiopulmonary bypass in older cardiac surgery patients with increased frailty risk

2区 · 医学

Article

作者: Schreurs, Inge A A M ; Vernooij, Lisette M ; Noordzij, Peter G ; van Dongen, Eric P A ; Smoor, Rosa M ; Verwijmeren, Lisa ; van Klei, Wilton A

Abstract:

:

OBJECTIVES:

Older patients have a higher cardiac surgery-associated acute kidney injury (CSA-AKI) related mortality. Low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) is a risk factor for CSA-AKI, but critical DO2 thresholds for older patients are unknown. This study investigated critical DO2 thresholds for CSA-AKI in patients ≥70 years undergoing on-pump cardiac surgery.

METHODS:

Patients were enrolled from July 2015 until August 2017. CPB data from 432 patients were collected, and DO2 values were calculated per minute. The primary outcome was CSA-AKI. The association between DO2 and CSA-AKI was analysed with multivariable regression analysis. Multiple DO2 thresholds were analysed. The association between CSA-AKI and the area below the DO2 thresholds (DO2 deficit) was evaluated, as was the association between frailty and CSA-AKI.

RESULTS:

CSA-AKI occurred in 63 (14.6%) patients. Mean and nadir (lowest) DO2 values were lower in patients with CSA-AKI (283 vs 312 ml/min/m2; P-value <0.001 and 238 vs 270 ml/min/m2; P-value <0.001, respectively). The adjusted relative risk for CSA-AKI was 1.006 [99% confidence interval (CI) 1.001–1.012] per ml/min/m2 nadir DO2 decrease. The critical DO2 threshold was 270 ml/min/m2 [adjusted relative risk 2.06 (99% CI 1.33–2.80)]. The DO2 deficit below 270 ml/min/m2 was associated with CSA-AKI [adjusted relative risk 2.84 (99% CI 1.87–3.81)]. No association between frailty and CSA-AKI was found (P = 0.82).

CONCLUSIONS:

Low DO2 increased the risk for CSA-AKI in older patients who had cardiac surgery. A critical DO2 threshold of 270 ml/min/m2 was applicable for frail and non-frail patients. The efficacy of a DO2 >270 ml/min/m2 to reduce CSA-AKI in older patients needs further evaluation.

2019-07-25·Investigative ophthalmology & visual science2区 · 医学

Alterations in Retinal Oxygen Delivery, Metabolism, and Extraction Fraction During Bilateral Common Carotid Artery Occlusion in Rats

2区 · 医学

ArticleOA

作者: Shahidi, Mahnaz ; Blair, Norman P. ; Farzad, Shayan ; Burford, James ; Karamian, Preny

Purpose:

The purpose of the current study was to investigate alterations in retinal oxygen delivery, metabolism, and extraction fraction and elucidate their relationships in an experimental model of retinal ischemia.

Methods:

We subjected 14 rats to permanent bilateral common carotid artery occlusion using clamp or suture ligation, or they underwent sham procedure. Within 30 minutes of the procedure, phosphorescence lifetime imaging was performed to measure retinal vascular oxygen tension and derive arterial and venous oxygen contents, and arteriovenous oxygen content difference. Fluorescent microsphere and red-free retinal imaging were performed to measure total retinal blood flow. Retinal oxygen delivery rate (DO2), oxygen metabolism rate (MO2), and oxygen extraction fraction (OEF) were calculated.

Results:

DO2 and MO2 were lower in ligation and clamp groups compared to the sham group, and also lower in the ligation group compared to the clamp group (P ≤ 0.05). OEF was higher in the ligation group compared to clamp and sham groups (P ≤ 0.03). The relationships of MO2 and OEF with DO2 were mathematically modeled by exponential functions. With moderate DO2 reductions, OEF increased while MO2 minimally decreased. Under severe DO2 reductions, OEF reached a maximum value and subsequently MO2 decreased with DO2.

Conclusions:

The findings improve knowledge of mechanisms that can maintain MO2 and may clarify the pathophysiology of retinal ischemic injury.

2014-02-13·The journal of physical chemistry. A3区 · 化学

Direct Kinetic Study of OH and O₃ Formation in the Reaction of CH₃C(O)O₂ with HO₂

3区 · 化学

Article

作者: Lelieveld, J. ; Groß, C. B. M. ; Schuster, G. ; Crowley, J. N. ; Dillon, T. J.

The reaction between HO2 and CH3C(O)O2 has three exothermic product channels, forming OH (R3a), peracetic acid (R3b), and acetic acid plus O3 (R3c). The branching ratios of the OH- and ozone-forming reaction channels were determined using a combination of laser-induced fluorescence (LIF, for time-resolved OH concentration measurement) and transient absorption spectroscopy (TAS, for time-resolved O3 concentration measurement) following pulsed laser generation of HO2 and CH3C(O)O2 from suitable precursors. TAS was also used to determine the initial concentration of the reactant peroxy radicals. The data were evaluated by numerical simulation using kinetic models of the measured concentration profiles; a Monte Carlo approach was used to estimate the uncertainties of the rate constants (k3) and branching ratios (α) thus obtained. The reaction channel forming OH (R3a) was found to be the most important with α3a = 0.61 ± 0.09 and α3c = 0.16 ± 0.08. The overall rate coefficient of the title reaction was found to be k3 = (2.1 ± 0.4) × 10(-11) cm(3) molecule(-1) s(-1) for both HO2 and DO2. Use of DO2 resulted in an increase in α3a to 0.80 ± 0.14. Comparison with former studies shows that OH formation via (R3) has been underestimated significantly to date. Possible reasons for these discrepancies and atmospheric implications are discussed.

1

项与 DO-2 相关的新闻（医药）

2021-02-24

·BioSpace

Newton Biocapital invests in Flemish startup DeuterOncology

Brussels, Belgium, 24 February 2021 – Newton Biocapital I (“Newton Biocapital”), a life sciences investment fund active in Europe and Japan focused on chronic diseases, has announced investment in DeuterOncology. Newton Biocapital’s second investment in Flanders, DeuterOncology is a preclinical-stage biotech company focusing on the development of a first-in-class dual MET and RAS pathway inhibitor for targeted cancer therapies. Recently MET inhibitors have been approved, yet they all suffer from the same issue: resistance is quick to arise. As the RAS pathway is located downstream of MET, RAS pathway inhibitors represent a promising new target for overcoming or delaying these resistance issues. DeuterOncology’s lead compound DO-2 is a dual MET and RAS pathway inhibitor under pre-clinical investigation as a targeted therapy for lung cancer, as well as potential broader oncology applications when used in combination with EGFR inhibitors. Timothy Perera, founder and CEO of DeuterOncology: “We are grateful for the financial support of Newton Biocapital, which will help us to advance the development of our lead program DO-2 towards Phase I clinical trials. Our compounds have the potential to overcome resistance to MET inhibitors, and we are excited that this funding brings us a step closer to offering our cancer solutions to clinicians and patients.” Els Hubloux, partner at Newton Biocapital Partners: “DeuterOncology brings a wealth of experience in pre-clinical and clinical research, for kinase inhibitors in general and particularly for MET inhibitors. Newton Biocapital is proud to take DeuterOncology into its portfolio, with the ambition to bring novel treatment approaches for cancer patients closer to market.” About DeuterOncology DeuterOncology was founded in September 2020 by Timothy Perera in Flanders, Belgium. The company is focused on the pre-clinical validation and development of DO-2, a novel MET and RAS pathway inhibitor sublicensed (worldwide rights outside of greater China) from OCTIMET Oncology NV and originally licensed from Janssen Pharmaceutica in 2017. DeuterOncology’s portfolio contains a sublicense to the all OCTIMET compounds, includes a clinical-stage MET kinase inhibitor that has been evaluated in both a monotherapy and combination therapy setting in cancer patients in Europe. DeuterOncology works together with a broad established network of collaborators across the world to try to bring new solutions to cancer patients. About Newton Biocapital Newton Biocapital I is a Venture Capital Firm incorporated in Belgium, focused on financing biotech and life science projects in Europe and Japan for the prevention and treatment of chronic diseases. The fund’s approach as lead investor is to support promising start-up projects as well as neglected or undervalued late-stage projects, in order to mitigate the risks and to create investor value. The leadership team consists of specialists with long-standing management and investor experience who coach bio-entrepreneurs through the development stages of their projects. Newton Biocapital’s mission is to generate substantial financial and societal value by providing innovative, breakthrough, and affordable solutions to patients.

合作First in Class引进/卖出

100 项与 DO-2 相关的药物交易

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研发状态

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
肺癌	临床1期	-	DeuterOncology SA初创企业	2023-06-07
晚期恶性实体瘤	临床1期	比利时	DeuterOncology SA初创企业	2022-12-20
晚期恶性实体瘤	临床1期	法国	DeuterOncology SA初创企业	2022-12-20
晚期恶性实体瘤	临床1期	荷兰	DeuterOncology SA初创企业	2022-12-20
非小细胞肺癌	临床1期	比利时	DeuterOncology SA初创企业	2022-12-20
非小细胞肺癌	临床1期	法国	DeuterOncology SA初创企业	2022-12-20
非小细胞肺癌	临床1期	荷兰	DeuterOncology SA初创企业	2022-12-20
难治恶性实体肿瘤	临床1期	比利时	DeuterOncology SA初创企业	2022-12-20
难治恶性实体肿瘤	临床1期	法国	DeuterOncology SA初创企业	2022-12-20
难治恶性实体肿瘤	临床1期	荷兰	DeuterOncology SA初创企业	2022-12-20