Manganese butoxyethyl pyridyl porphyrin

藻胆体（phycobilisome）是蓝细菌和红藻光合系统的关键结构，通过蛋白骨架定位色素团分子（bilins）高效捕获光能并传递到光系统I/II及反应中心，进而实现光能到化学能转化。 藻胆体（phycobilisome）是蓝细菌和红藻光合系统的关键结构，通过蛋白骨架定位色素团分子（bilins）高效捕获光能并传递到光系统I/II及反应中心，进而实现光能到化学能转化。利用超分子组装策略模拟光合细菌或藻类的光捕获及反应中心结构，对探索新型人工光合系统具有重要意义，其核心是构建人工骨架来模拟载脂蛋白控制色素分子的空间排列，进而实现光捕获和光反应的高效耦合。藻胆体是典型的天然光合组装结构，为新型超分子人工光合系统的构筑提供了重要思路。中国科学院上海有机化学研究所研究员田佳致力于构建人工光合组装体系统以实现光能向化学能的高效转化与储存，于2023年报道了首例仿光合紫菌色素体构筑的有机超分子人工光合组装体用于水相常温高效CO2还原。  近日，田佳及合作者在仿藻胆体构建水相人工光合组装体用于光催化产H2研究中取得了进展。相关研究成果以Bioinspired Self-Assembly of Metalloporphyrins and Polyelectrolytes into Hierarchical Supramolecular Nanostructures for Enhanced Photocatalytic H2 Production in Water为题，在线发表在《德国应用化学》上。  该工作受蓝细菌藻胆体启发，人工组装体结构通过聚电解质PDDA模拟蛋白质骨架的同时利用金属卟啉模拟色素团分子得以实现。在水中，阳离子型PDDA与具有光敏和催化功能的阴离子型金属卟啉共组装生成一维光合组装体，从而模拟藻胆体棒状天线结构和催化中心（图1）。该光合组装结构可实现水相光催化产H2，其效率相比单体分子提升23倍以上。通过形成纳米组装结构，光敏和催化金属卟啉的光稳定性相对单体结构显著提升。研究进一步借助瞬态吸收光谱、荧光光谱和理论计算研究了光催化机制（图2）。光照后，研究通过飞秒级瞬态吸收光谱观察到有金属卟啉阳离子自由基生成，说明可能存在光诱导的电子转移过程；理论计算同时支持镁卟啉与铜卟啉之间通过电子转移生成电荷分离态。此外，荧光光谱和瞬态吸收光谱实验支持光合组装体内存在能量转移过程。因此，该仿生组装体系统中的光敏金属卟啉可以通过能量转移和电子转移协同过程使光能从光敏剂传递至光催化中心，从而实现了高效的水相光催化质子还原产H2。通过优化光催化条件，该组装体的光催化产H2性能显著优于其他金属卟啉组装体系。光照下，此光合组装体的产氢速率和转化数（TON）可达51,776 μmol h-1 g-1和1299。该研究不仅加深了科学家对天然藻胆体光合作用结构与机制的认知，而且为构筑水相仿生超分子光合组装体系统提供了新思路。  研究工作得到国家重点研发计划、国家自然科学基金委员会、中国科学院和上海市科学技术委员会等的支持。 图1. 受藻胆体启发的仿生光合组装体构筑示意图  图2. 仿生光合组装体的光催化机制研究

BMX-001 has the potential to augment tumor killing by radiation therapy and inhibits tumor regrowth by inhibiting pro-survival and pro-angiogenic transcription factors and HIF-1a In Phase 2 study, BMX-001 demonstrates increased overall survival and tolerable safety pro > GREENWOOD VILLAGE, Colo.--(BUSINESS WIRE)-- BioMimetix JV, LLC, a clinical-stage biotechnology company developing metalloporphyrins, a novel drug class for the treatment of cancer patients, today announced the presentation of encouraging data from its Phase 2 study of lead candidate, BMX-001, for the treatment of high-grade glioma (HGG) at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting. In the Phase 2 study, BMX-001 in combination with radiotherapy (RT) and temozolomide (TMZ) demonstrated a 6.6 month increase in median survival, mitigation of radiation-induced cognitive issues, and improved white matter integrity with a tolerable safety profile, compared to current standard of care. The abstract will be published in SNO’s official journal, Neuro-Oncology. “Patients with high grade glioma are challenging to treat because the disease grows quickly, ultimately outcomes are very poor for these patients and often carries an unfavorable prognosis. Current treatments aim to remove the tumor through surgery or slow its growth using chemotherapy and radiation therapy, but they are not curative and are associated with significant toxicities, including radiation-induced cognitive dysfunction that is responsible for negatively impacting the quality of life for our patients. The diversity of cases makes finding a cure difficult, and seeing durable responses in these patients is encouraging,” said Katy Peters, MD PhD FAAN (Lead Principal Investigator). “BMX-001 is a promising first-in-class molecule with clinically meaningful activity and the potential to become a new treatment option for patients diagnosed with high grade glioma.” “The exciting data presented today at SNO underscore what I have sought to achieve over the past several decades in our scientific research. The primary mechanism of action of a redox active metalloporphyrin is modulation of key pathways of cellular signaling in a pattern that augments radiation therapy in killing tumor cells while protecting normal tissues. This is demonstrated by the promising effects seen in this trial with BMX-001 on patients with high grade glioma receiving concurrent radiation and chemotherapies,” said James Crapo, M.D., Chief Executive Officer at BioMimetix. “High grade glioma is an aggressive brain cancer with a low survival rate that affects 10,000-15,000 people in the US per year. A substantial increase in median survival over the standard of care coupled with improved quality of life represents a significant stride towards bringing patients a transformative treatment. We are motivated to continue developing BMX-001 for this area of high unmet need, while also continuing to explore the utility of BMX-001 in other cancer types.” Presentation Highlights: The Phase 2 clinical trial included 160 subjects with newly diagnosed high grade glioma of which 145 completed protocol treatment. Patients on concurrent RT/TMZ who also received BMX-001 were found to have an increased median survival of 6.6 months. BMX-001 also mitigated radiation-induced cognitive issues - demonstrated by an increase in Hopkins Verbal Learning Test scores at 6-months post-baseline versus the control group, and an improvement in Brief Assessment of Cognition (BAC) scores. BMX-001 was found to have an excellent safety profile. Presentation Details: Title: Results of BMX-HGG study: a multi-institutional, randomized phase 2 clinical trial of concurrent chemoradiation with or without BMX-001 in patients with newly diagnosed high-grade glioma Abstract Number: LTBK-09 Date and Time: Friday, November 17, 2023, from 9:05 – 9:15 a.m. PT Session: Plenary I, Exhibit Hall C Presenter: Katherine Peters, M.D., Duke University Medical Center About BMX-001 BMX-001 is a metalloporphyrin, a novel class of redox-active, small molecule. The active center is designed to mimic the center of superoxide dismutase. The primary mechanism of action is modulation of cellular signaling pathways. BMX-001 inhibits both NFkB and HIF-1a. By inhibiting these pro-survival and pro-angiogenic transcription factors, BMX-001 augments tumor killing by radiation therapy and inhibits tumor regrowth. The inhibition of NFkB blocks major components of the inflammatory cascade which simultaneously results in protection of normal tissue from radiation induced injury. BMX-001 is also being developed in head and neck cancer, anal cancer, and rectal cancer and has been previously granted Orphan, Fast Track and Breakthrough designations by the FDA. About BioMimetix JV, LLC BioMimetix JV, LLC is a clinical-stage biotechnology company developing a novel platform drug class, metalloporphyrins, that enhances the effectiveness and safety of chemoradiation for the treatment of cancer patients. The Company’s robust clinical pipeline spanning multiple oncology indications is supported by demonstrated clinical efficacy in multiple ongoing clinical studies and extensive preclinical data.