更新于：2024-11-01

KAT2B

更新于：2024-11-01

基本信息

别名

GCN5、GCN5L、Histone acetylase PCAF

+ [9]

简介

Functions as a histone acetyltransferase (HAT) to promote transcriptional activation (PubMed:8945521). Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles (PubMed:8945521). Also acetylates non-histone proteins, such as ACLY, MAPRE1/EB1, PLK4, RRP9/U3-55K and TBX5 (PubMed:9707565, PubMed:10675335, PubMed:23001180, PubMed:27796307, PubMed:23932781, PubMed:26867678, PubMed:29174768). Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A (PubMed:8684459). Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing (PubMed:26867678). Acetylates MAPRE1/EB1, promoting dynamic kinetochore-microtubule interactions in early mitosis (PubMed:23001180). Also acetylates spermidine (PubMed:27389534). (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.

关联

项与 KAT2B 相关的药物

GSK699

靶点

KAT2A x KAT2B

作用机制

KAT2A 降解剂 [+1]

在研机构

GSK Plc

原研机构-

在研适应症

炎症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

AUTX-703

靶点

KAT2A x KAT2B

作用机制

KAT2A 降解剂 [+1]

在研机构

Auron Therapeutics, Inc.初创企业

原研机构

Auron Therapeutics, Inc.初创企业

在研适应症

急性髓性白血病 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

GSK702

靶点

KAT2B

作用机制

KAT2B 降解剂

在研机构

GSK Plc

原研机构-

在研适应症

炎症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 KAT2B 相关的临床结果

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100 项与 KAT2B 相关的转化医学

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0 项与 KAT2B 相关的专利（医药）

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1,112

项与 KAT2B 相关的文献（医药）

2024-12-01·Antonie van Leeuwenhoek

Paracoccus benzoatiresistens sp. nov., a benzoate resistance and selenite reduction bacterium isolated from wetland

Article

作者: Wang, Kaiyue ; Mu, Weidong ; Liu, Hongliang ; Liu, Haoran ; Song, Jianjun ; Liu, Aijv ; Li, Xiuyun ; Wei, Shuzhen ; Hu, Jinhua ; Guo, Bai

A Gram-stain-negative, aerobic, non-motile, catalase- and oxidase-positive, pale orange, rod-shaped strain EF6^T, was isolated from a natural wetland reserve in Hebei province, China. The strain grew at 25-37 °C (optimum, 30 °C), pH 5-9 (optimum, pH 7), and in the presence of 1.0-4.0% (w/v) NaCl (optimum, 2%). A phylogenetic analysis based on 16S rRNA gene sequence revealed that strain EF6^T belongs to the genus Paracoccus, and the closest members were Paracoccus shandongensis wg2^T with 98.1% similarity, Paracoccus fontiphilus MVW-1^T (97.9%), Paracoccus everestensis S8-55^T (97.7%), Paracoccus subflavus GY0581^T (97.6%), Paracoccus sediminis CMB17^T (97.3%), Paracoccus caeni MJ17^T (97.0%), and Paracoccus angustae E6^T (97.0%). The genome size of strain EF6^T was 4.88 Mb, and the DNA G + C content was 65.3%. The digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between strain EF6^T and the reference strains were all below the threshold limit for species delineation (< 32.8%, < 88.0%, and < 86.7%, respectively). The major fatty acids (≥ 5.0%) were summed feature 8 (86.3%, C_18:1 ω6c and/or C_18:1 ω7c) and C_18:1 (5.0%) and the only isoprenoid quinone was Q-10. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids, five unidentified phospholipids, and an unidentified aminolipid. Strain EF6^T displays notable resistance to benzoate and selenite, with higher tolerance levels (25 g/L for benzoate and 150 mM for selenite) compared to the closely related species. Genomic analysis identified six benzoate resistance genes (acdA, pcaF, fadA, pcaC, purB, and catA) and twenty selenite resistance and reduction-related genes (iscR, ssuB, ssuD, selA, selD and so on). Additionally, EF6^T possesses unique genes (catA, ssuB, and ssuC) absent in the closely related species for benzoate and selenite resistance. Its robust resistance to benzoate and selenite, coupled with its genomic makeup, make EF6^T a promising candidate for the remediation of both organic and inorganic pollutants. It is worth noting that the specific resistance phenotypes described above were not reported in other novel species in Paracoccus. Based on the results of biochemical, physiological, phylogenetic, and chemotaxonomic analyses, combined with comparisons of the 16S rRNA gene sequence and the whole genome sequence, strain EF6^T is considered to represent a novel species of the genus Paracoccus within the family Rhodobacteraceae, for which the name Paracoccus benzoatiresistens sp. nov. is proposed. The type strain is EF6^T (= GDMCC 1.3400^T = JCM 35642^T = MCCC 1K08702^T).

2024-12-01·Cellular and Molecular Life Sciences

Vascular injury activates the ELK1/SND1/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia

Article

作者: Wei, Minxin ; Xin, Lingbiao ; Ma, Jinzheng ; Hao, Wei ; Liu, Mingxia ; Su, Chao ; Ren, Yuanyuan ; Yu, Ying ; Gao, Xingjie ; Yang, Jie ; Ge, Lin ; Yao, Xuyang

AbstractBackgroundVascular smooth muscle cell (VSMC) proliferation is the leading cause of vascular stenosis or restenosis. Therefore, investigating the molecular mechanisms and pivotal regulators of the proliferative VSMC phenotype is imperative for precisely preventing neointimal hyperplasia in vascular disease.MethodsWire-induced vascular injury and aortic culture models were used to detect the expression of staphylococcal nuclease domain-containing protein 1 (SND1). SMC-specific Snd1 knockout mice were used to assess the potential roles of SND1 after vascular injury. Primary VSMCs were cultured to evaluate SND1 function on VSMC phenotype switching, as well as to investigate the mechanism by which SND1 regulates the VSMC proliferative phenotype.ResultsPhenotype-switched proliferative VSMCs exhibited higher SND1 protein expression compared to the differentiated VSMCs. This result was replicated in primary VSMCs treated with platelet-derived growth factor (PDGF). In the injury model, specific knockout of Snd1 in mouse VSMCs reduced neointimal hyperplasia. We then revealed that ETS transcription factor ELK1 (ELK1) exhibited upregulation and activation in proliferative VSMCs, and acted as a novel transcription factor to induce the gene transcriptional activation of Snd1. Subsequently, the upregulated SND1 is associated with serum response factor (SRF) by competing with myocardin (MYOCD). As a co-activator of SRF, SND1 recruited the lysine acetyltransferase 2B (KAT2B) to the promoter regions leading to the histone acetylation, consequently promoted SRF to recognize the specific CArG motif, and enhanced the proliferation- and migration-related gene transcriptional activation.ConclusionsThe present study identifies ELK1/SND1/SRF as a novel pathway in promoting the proliferative VSMC phenotype and neointimal hyperplasia in vascular injury, predisposing the vessels to pathological remodeling. This provides a potential therapeutic target for vascular stenosis.Graphical abstract

2024-12-01·Plant Science

Lysine 98 in NAC20/NAC26 transcription factors: a key regulator of starch and protein synthesis in rice endosperm

Article

作者: Xu, Shanbin ; Zhang, Guiping ; Dong, Hui ; Gu, Chuanwei ; Cai, Hongping ; Wang, Yihua ; Ren, Yulong ; Teng, Xuan ; Duan, Erchao ; Chen, Rongbo ; Jiang, Ling ; Chen, Laibao ; Wan, Jianmin ; Zhang, Yu ; He, Yuzhe

Starch and proteins are main storage product to determine the appearance, cooking, texture, and nutritional quality of rice (Oryza sativa L.). OsNAC20 and OsNAC26, as pivotal transcription factors, redundantly regulate the expression of genes responsible for starch and protein synthesis in the rice endosperm. Any knockout of OsNAC20 or OsNAC26 did not result in visible endosperm defects. In this study, we had isolated and characterized a mutant named as floury endosperm25 (flo25). The caryopsis of the flo25 mutant exhibits a floury endosperm, accompanied by reductions in both the 1000-grain weight and grain length, as well as diminished levels of total starch and protein. Through map-based cloning, it was determined that FLO25 encodes a NAM, ATAF, and CUC (NAC) transcription factors, namely OsNAC26, with a lysine to asparagine substitution at position 98 in the flo25 mutant. Remarkably, lysine 98 is conserved across plants species, and this mutation does not alter the subcellular localization of OsNAC26 but significantly attenuates its transcriptional activity and its ability to activate downstream target genes. Furthermore, the mutant protein encoded by OsNAC26^-flo25 could interact with OsNAC20, disrupting the native interaction between OsNAC20 proteins. Additionally, when lysine 98 is substituted with asparagine in OsNAC20, the resulting mutant protein, OsNAC20(K98N), similarly disrupts the interaction between OsNAC26 proteins. Collectively, these findings underscore the pivotal role of Lysine 98 (K) in modulating the transcriptional activity of NAC20/NAC26 within the rice endosperm.

项与 KAT2B 相关的新闻（医药）

2024-10-11

·BioSpace

Auron Announces Poster Presentation at 2024 PCF Annual Scientific Retreat

NEWTON, Mass., Oct. 11, 2024 (GLOBE NEWSWIRE) -- Auron Therapeutics , a biotechnology company focused on developing next-generation targeted therapies by identifying and inhibiting the oncogenic cell states of cancer, today announced that the Company will present updated preclinical data from its lead program during a poster session at the 31st Annual Prostate Cancer Foundation (PCF) Annual Scientific Retreat from October 24-26, 2024 in Carlsbad, CA. At PCF, Auron will present in vitro and in vivo data from AUTX-703, its oral, potent and selective degrader of KAT2A/B that is being developed for the treatment of AML and neuroendocrine carcinomas including SCLC and NEPC. Auron is on-track to submit an Investigational New Drug (IND) application for AUTX-703 in late 2024 for initiation of clinical development in early 2025. Details for Auron’s presentation at the PCF Annual Scientific Retreat are below: Abstract Title: AUTX-703, a Highly Potent and selective KAT2A and KAT2B Protein Degrader, Induces Cell State Changes and Inhibits Growth in NEPC and SCLC Cancers Session Date and Time: Thursday, October 24, 7:30 - 10:30 p.m. PT About Auron Therapeutics Auron Therapeutics is a patient-centered, platform-powered, product-driven oncology company. Auron is leading the next generation of targeted cancer therapies by identifying and inhibiting the oncogenic cell states of cancer. Auron pioneered its AURIGIN™ platform, which uses AI and machine learning to compare normal cell states with cancerous cell states to identify novel cancer targets, optimal development models, and biomarkers to facilitate proper patient selection. Using AURIGIN, the Company is building a pipeline of small molecule targeted therapies, led by AUTX-703, which is being developed for the treatment of both solid tumors, including small cell lung cancer and neuroendocrine prostate cancer, and hematologic malignancies, including acute myeloid leukemia. For more information, please visit aurontx.com . Investor Contact: Renee Leck THRUST Strategic Communications renee@thrustsc.com

临床申请

2024-10-09

·GlobeNewswire-Health Care

Auron to Present AUTX-703 Preclinical Data 2024 ENA Symposium

NEWTON, Mass., Oct. 09, 2024 (GLOBE NEWSWIRE) -- Auron Therapeutics, a biotechnology company focused on developing next-generation targeted therapies by identifying and inhibiting the oncogenic cell states of cancer, today announced that the Company will present updated preclinical data from its lead program during a poster session at the 36th EORTC-NCI-AACR (ENA) Symposium from October 23-25, 2024 in Barcelona, Spain. At ENA, Auron will present in vitro and in vivo data from AUTX-703 its oral, potent and selective degrader targeting KAT2A/B, a histone acetyltransferase that is associated with multiple tumor types, including SCLC. Auron is on-track to submit an Investigational New Drug (IND) application for AUTX-703 in late 2024 for initiation of clinical development in early 2025. Details for Auron’s poster presentation are below: Abstract Title: AUTX-703, a Novel and Potent KAT2A and KAT2B Protein Degrader, Induces Profound Cell State Changes and Inhibits Growth on Small Cell Lung Cancer (SCLC) Model SystemsPoster Session: Molecular Targeted Agents Session Date and Time: Wednesday, October 23, 12:00 - 7:00 p.m. CET About Auron Therapeutics Auron Therapeutics is a patient-centered, platform-powered, product-driven oncology company. Auron is leading the next generation of targeted cancer therapies by identifying and inhibiting the oncogenic cell states of cancer. Auron pioneered its AURIGIN™ platform, which uses AI and machine learning to compare normal cell states with cancerous cell states to identify novel cancer targets, optimal development models, and biomarkers to facilitate proper patient selection. Using AURIGIN, the Company is building a pipeline of small molecule targeted therapies, led by AUTX-703, which is being developed for the treatment of both solid tumors, including small cell lung cancer and neuroendocrine prostate cancer, and hematologic malignancies, including acute myeloid leukemia. For more information, please visit aurontx.com. Investor Contact: Renee LeckTHRUST Strategic Communicationsrenee@thrustsc.com

AACR会议临床申请

2024-09-28

·BiG生物创新社

当PROTAC遇上自免，临床表现及潜力如何？

作者｜小鱼摘要：由于自身免疫性疾病病理机制的复杂性以及临床的异质性，患者需要个性化医疗和精准靶向治疗策略，蛋白质水解靶向嵌合体（PROTACs）能够满足临床自免治疗的所有想象，克服传统自免疗法的局限，且鹤立于一众靶向药物，其中进展最快的管线已推至临床2期。引言：自身免疫性疾病作为继肿瘤之后下一个大的治疗领域，弗若斯特沙利文预测，到2030年，全球自免药物市场规模有望达到1760亿美元，2022~2030年复合年增长率为3.6%。不幸的是，自免的治疗水平和研究深度远不及肿瘤，甚至像糖皮质激素这样有严重副作用的药物，仍在用于治疗许多非特定的自免疾病。幸运的是，自免被越来越多的临床医生和研究机构所关注。许多前沿的生物技术涌入自免治疗领域，甚至把还处于临床阶段的肿瘤治疗明星PROTAC，都拿来开发用于治疗自免疾病，但这绝不是研究者脑袋一热、毫无根据的拿来，而是基于PROTAC特点与自免研究现状的科学判断。上一期，我们分享了针对炎症靶点开发治疗自免的PROTAC，本文将从自免疗法的发展脉络出发，探讨目前治疗的局限性，分析PROTACs能够破局并成为首选靶向药物的关键，最后根据PROTACs在自免领域的临床表现，预测其临床前景。图1 通过PROTAs靶向治疗自身免疫性疾病的图解 01 自身免疫性疾病仍存在大量的未被满足的临床需求自身免疫性疾病是指免疫系统错误地攻击和破坏身体正常组织和器官的一类疾病。这类疾病的具体原因尚不完全清楚，但遗传因素、环境因素和免疫系统失调等因素可能都起到一定的作用。目前已知的主要疾病类型包括银屑病、特应性皮炎、强制性脊柱炎、类风湿性关节炎以及系统性红斑狼疮等100多种。作为慢性疾病，自免疾病通常不会直接致死，但也难以根治。如强制性脊柱炎、系统性红斑狼疮等，一旦患则将难以逆转，被称为“不死癌症”。自身免疫性疾病的治疗手段经历了从非特异性治疗到靶向治疗的发展历程，未被满足的临床需求巨大： 1.1传统系统性药物疗效有限，非特异性治疗副作用大 ①糖皮质激素 20世纪40年代的治疗手段为使用糖皮质激素，如泼尼松，长期使用副作用大，会对骨骼、心血管系统和代谢功能产生严重毒性，可引起激素依赖性皮炎、加重高血压、诱发或加重患者胃、十二指肠溃疡以及绝经妇女骨质疏松，导致人体肌肉萎缩、延缓伤口愈合和青光眼等。突然停药后易复发。虽然随着时间的推移减少了激素的使用，但目前在系统性红斑狼疮等自免疾病的指南中，对于中重度患者依然推荐使用糖皮质激素治疗。 ②非选择性免疫抑制剂 90年代后期，非选择性免疫抑制剂被广泛使用，如甲氨蝶呤、硫唑嘌呤、磺胺沙拉嗪、羟氯喹、D-潘利霉素、霉酚酸盐等，它们能够减缓疾病进展，但缺乏特异性，起效较慢，对已损伤组织无显著修复能力。由于对整个免疫系统进行抑制，提高了癌症等病症的风险。现已在临床上普遍使用。 1.2 靶向药物存在耐药性，仅针对少部分自免疾病靶向药物是自身免疫性疾病的最佳治疗选择，选择性地抑制免疫系统，从而可以适当减少副作用的产生，起效更快。但其所治疗的适应症分布较为集中，主要聚焦于类风湿关节炎、银屑病、强直性脊柱炎、肠胃疾病等几个领域，而自免领域共包含100余种不同疾病。因此，大量适应症缺少靶向药物，但现有的靶向药物，如抗体类药物和小分子抑制剂，只能覆盖整个人体中20-25%的药物靶点。 ①单克隆抗体疗法进入21世纪后，生物制剂如肿瘤坏死因子（TNF）α抑制剂（例如英夫利昔单抗、阿达木单抗）、IL-6受体拮抗剂（如托珠单抗）、抗CD20单克隆抗体、IL-1受体拮抗剂等开始用于临床，这些药物能够更精确地作用于特定的免疫介质，减少副作用。但是约有40%的患者对TNF-α单抗具有耐药性。其次，单克隆抗体分子量大，生物利用度低，在体内的作用效力很有限，且成本高昂。 ②小分子抑制剂相比之下，小分子与单克隆抗体相比，表现出更好的药代动力学特征。近年来，JAK-STAT途径的小分子抑制剂（如托法替尼、巴瑞克替尼）成为治疗自身免疫性疾病的新选择，它们通过抑制特定的信号转导途径来发挥作用。但在较高剂量下，产生脱靶效应，引起感染、血脂异常等不良反应。合并所有的现实情况，我们迫切需要一种新的靶向生物技术。 02 PRTOACs在自免靶向治疗中脱颖而出的“资本” 2001年，Crews和Deshaies团队提出了PROTAC这一开创性概念。经过20多年的发展，这项蛋白降解技术已经从学术界发展到工业界。PROTACs的作用机制已在大量的报道中阐述。图2 PROTAC的作用机制作为一种双功能小分子化合物，PROTAC类似一个跷跷板，一端是结合靶蛋白的配体，另一端是结合E3泛素连接酶的配体，配体之间通过一个linker连接，形成一个复合物，拉近靶蛋白与E3连接酶从而促进靶蛋白的泛素化，使其进入泛素-蛋白酶体降解途径，达到降解靶蛋白的目的。从分子结构和作用机制来看，PROTAC都是治疗自免的不二之选： 2.1 PROTAC能够靶向不可药物化的蛋白传统的靶向药需要与目标蛋白（通常是其活性位点）牢固结合，但许多与自身免疫性疾病相关的蛋白质可能缺乏活性位点，难以通过传统小分子或生物制剂进行靶向。而PROTAC仅需与目标蛋白弱结合便能对其进行特异性“标记”，因此，PROTAC可能解决目前“不可成药”的约80%蛋白质组，比如KRAS、Tau蛋白、α-突触核蛋白、PCAF/GCN5、EGFR突变体、BTK等。 2.2 PROTAC能够降低副作用自身免疫性治疗多数时候呈现出疗效与副作用同步增长的趋势，随着疾病的加重，用药的选择，更高的剂量，长期用药，药物累积效应等，免疫系统大规模关闭，给患者带来越来越严重的不良反应。PROTAC或许能够破解这个难题。 ①提高治疗选择性 PROTACs通过设计可以特异性地靶向特定的E3泛素连接酶，从而实现对目标蛋白的精确降解。这种高度的选择性有助于减少非目标蛋白的降解，降低副作用。 ②平衡剂量和疗效 PROTAC催化目标蛋白的降解，而不是仅仅与其结合。其次，相较于大分子药物，如单克隆抗体，小分子PROTACs通常具有更高的组织穿透率。上述作用机制和药代动力学特性允许PROTAC在较低剂量下实现治疗效果，降低副作用。 2.3 PROTAC能够克服耐药性在传统靶向治疗中，疾病相关蛋白可能会发生突变，导致药物失效。而PROTACs通过促进蛋白降解，而不是抑制其活性，可能绕过这种耐药性问题。上述是PROTAC比较显著的优势，此外PROTAC小分子还有口服治疗，提高患者依从性，拥有更低的生产成本等亮点。但PROTAC治疗自免纵有万般好，也要经受临床的考验，证明PROTAC的成药性。 03 PROTAC治疗自免的临床表现证明其成药潜力根据智慧芽新药情报库中数据显示，截至2024年9月25日，处于自免治疗临床阶段的有2款PROTAC，分别是Kymera的KT-474和百济神州的BGB-45035，处于临床2期和临床1期阶段，均靶向IRAK4。目前可获得的临床数据仅Kymera公布的KT-474临床1期数据，结果积极。现介绍如下： 3.1 KT-474小分子的开发背景 2020年，赛诺菲从Kymera获得授权，共同开发蛋白降解药物KT-474，总金额为21.5亿美元，包括1.5亿美元的首期付款和里程碑付款。图3 KT-474分子结构 KT-474由通过linker连接E3泛素连接酶cereblon （CRBN）配体和IRAK4 结合配体，将IRAK4募集至CRBN进行泛素化和蛋白酶体降解。IRAK4是一种关键信号转导基因，也是Toll信号通路下游最近的激酶，是先天免疫的关键介质。IRAK4过度激活与多种自身免疫性疾病有关，例如MS、SLE和银屑病。 3.2 KT-474具有良好的安全性和耐受性在 I 期临床试验中，招募了105名健康志愿者和21名患有中度至重度化脓性汗腺炎（HS）或特应性皮炎（AD）的患者。 ①健康志愿者：单剂量高达1600 mg或每日剂量高达200 mg，持续14天，对PROTAC的耐受性良好，没有严重的副作用或药物相关感染。 ②HS或AD患者：观察到类似的安全性，他们每天接受75 mg KT-474治疗，持续28天。 3.3 KT-474能够改善AD和HS症状 ①KT-474对IRAK4的高选择性：连续14天服用KT-474后，来自患者或健康志愿者的PBMCs中的IRAK4水平降低了95%以上，还抑制了患者血浆中促炎细胞因子水平的升高。 ②KT-474的临床有效性：大多数HS或AD患者的皮损和症状在治疗过程中逐渐改善，尽管有两名非常严重的HS患者没有反应。12名HS患者中，皮损数量平均减少，疼痛和瘙痒减轻；治疗后两周的随访继续改善。7名AD患者的湿疹严重程度略有下降，瘙痒也有所减轻。图4 化脓性汗腺炎（HS）：终点包括AN计数、疼痛NRS、瘙痒NRS和HS-PGA。患者的HS-PGA稳定或改善。图5 特应性皮炎（AD）：终点包括EASI评分、峰值瘙痒NRS和vIGA-AD。患者的vIGA-AD均稳定或有所改善。小结鉴于篇幅有限，还有若干受瞩目的自免临床候选PROTACs没有提到，小编认为可以关注靶向BTK的PROTAC降解剂NX-5948I和L18，前者由Nurix Therapeutics公司开发，首先用于癌症治疗，处于临床1期阶段；后者的研究成果于今年8月由清华大学刘万里、饶燏及北京大学肿瘤医院丁宁等人发表在Cell Discovery期刊上。综上所述，PROTACs因其独特的作用机制和治疗潜力，有望成为自身免疫性疾病的下一代治疗药物。在临床应用中，PROTACs在一定程度上经受住了安全性、耐受性和有效性的考验，但挑战仍然存在，如提高溶解度、优化药代动力学特性以及长期治疗的安全性评估。随着研究的深入和技术的进步，这些挑战有望得到解决，从而进一步推动PROTACs在自免治疗中的应用。参考文献： https://doi.org/10.1039/D4MD00142G https://www.nature.com/articles/s41421-024-00711-x https://www.nurixtx.com/pipeline/ https://www.kymeratx.com/science-innovation/pipeline/ https://www.beigene.com.cn/our-science-and-medicines/pipeline/ https://www.polymedbiopharma.com/cn/Common/1265 https://synapse.zhihuiya.com/drug-list?query_id=5a617729-fd8a-42bb-a1ef-4cd01f18908a BiG近期会议 10.12日上午：自免研讨会 8:50-8:55 联合主办方致辞 8:55-9:00 联合主办方致辞涂欢：深圳医学科学院副院长、深圳湾实验室副主任 9:00-9:30 Keynote—炎症免疫检查点与AI驱动药物研发陈有海：美国医学与生物工程院士、欧洲科学院院士、深圳理工大学药学院院长 9:30-10:00 Keynote—临床视角，创新药开发自免，如何选择适应症？徐沪济：海军军医大学长征医院大内科主任兼风湿科主任/清华大学医学院教授 10:00-10:25 MNC视角，AZ在肿瘤+自免的布局和开发策略章宇：阿斯利康产品管线和项目管理副总裁 10:25-10:50 茶歇 10:50-11:40 Panel：自免创新药如何立项？MNC&biotech的布局策略，BD合作背后的故事？肖昌春：赛诺菲中国研究负责人、赛诺菲研究院负责人徐亚南：武田制药全球外部创新合作部中国区负责人邓天敬：炎明生物联合创始人/CEO 靳照宇：明济生物董事长兼CEO 朱向阳：华奥泰生物总经理周潇薇：松禾资本董事总经理（主持） 11:40-12:30 Panel：从肿瘤转战自免，创新疗法（CAR-T/CAR- NK/双抗/ADC/PROTAC等）如何选择适应症，不同modality各自开发优势及挑战，在哪里？未来有哪些新靶标值得关注？范晓虎：湾岛细胞创始人/CEO 花海清：映恩生物研发副总裁冯焱：领泰生物创始人/CEO 张雷：深圳湾实验室特聘研究员卢宏韬：科望医药联合创始人/CSO、BiG总干事（主持） 12:30 闭幕致辞&研讨会主持李圆：BiG秘书长 12:30-14:00 午餐&参观&自由交流 ● 深圳医学科学院（SMART）、卫光生命科学园、湾有引力（光明生物医药创新中心） 14:00 论坛闭幕报名入口 PS：免费席位有限，均为审核制观众门票：0元含12日自免会议&午餐；限biotech/Pharma、临床、院校科学家、投资机构代表共建Biomedical创新生态圈！如何加入BiG会员？

免疫疗法临床结果临床2期