更新于：2024-11-01

Aurora B

更新于：2024-11-01

基本信息

别名

极光激酶B、AIK2、AIM-1

+ [24]

简介

Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118). The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:26829474). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (PubMed:15249581). Required for central/midzone spindle assembly and cleavage furrow formation (PubMed:12458200, PubMed:12686604). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (PubMed:11516652, PubMed:12925766, PubMed:14610074). Phosphorylation of INCENP leads to increased AURKB activity (PubMed:11516652, PubMed:12925766, PubMed:14610074). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3 (PubMed:11784863, PubMed:12689593, PubMed:14602875, PubMed:11856369, PubMed:16103226, PubMed:21658950, PubMed:11756469). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (PubMed:21658950). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863, PubMed:11856369). AURKB is also required for kinetochore localization of BUB1 and SGO1 (PubMed:15020684, PubMed:17617734). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (PubMed:20959462). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (PubMed:33542149). Phosphorylates KRT5 during anaphase and telophase (By similarity).

关联

项与 Aurora B 相关的药物

Chiauranib

西奥罗尼

靶点

Aurora B x CSF-1R x VEGFR x c-Kit

作用机制

Aurora B抑制剂 [+3]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

AL-8326

靶点

Aurora B x FGFRs x VEGFR

作用机制

Aurora B抑制剂 [+2]

在研机构

南京爱德程医药科技有限公司 [+1]

原研机构

南京爱德程医药科技有限公司

在研适应症

小细胞肺癌 [+6]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

Tinengotinib

靶点

Aurora A x Aurora B x CSF-1R x FGFR1 x FGFR2 x FGFR3 x JAK1 x JAK2 x VEGFR

作用机制

Aurora A抑制剂 [+8]

在研机构

药捷安康（南京）科技股份有限公司初创企业

原研机构

药捷安康（南京）科技股份有限公司初创企业

在研适应症

胆管癌 [+11]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

111

项与 Aurora B 相关的临床试验

CTR20242363 / Recruiting临床2期

西奥罗尼联合白蛋白紫杉醇和吉西他滨一线治疗局部晚期或转移性胰腺导管腺癌患者的Ⅱ期临床研究

（1）主要目的：探索西奥罗尼联合白蛋白紫杉醇和吉西他滨一线治疗局部晚期或转移性胰腺导管腺癌患者的初步疗效。（2）次要目的：观察西奥罗尼联合白蛋白紫杉醇和吉西他滨一线治疗局部晚期或转移性胰腺导管腺癌患者的安全性，分析西奥罗尼联合化疗后的药代动力学（PK）特征。

开始日期2024-08-13

申办/合作机构

成都微芯药业有限公司

[+1]

NCT06492915 / Not yet recruiting临床2期

A Phase Ⅱ Study of Chiauranib Plus Albumin-paclitaxel and Gemcitabine as First-line Therapy in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma

Chiauranib , which simultaneously targets against VEGFR/Aurora B/CSF-1R, several key kinases involved in tumor angiogenesis, tumor cell mitosis, and chronic inflammatory microenvironment.

开始日期2024-08-01

申办/合作机构

深圳微芯生物科技股份有限公司

NCT06457919 / Recruiting临床1/2期IIT

A Phase 1b/2 Study Evaluating the Activity of Tinengotinib (TT-00420) in Combination With Androgen Receptor Signaling Inhibitors (ARSIs) in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

The purpose of this study is to find out whether tinengotinib in combination with abiraterone acetate and prednisone or enzalutamide is a safe treatment that causes few or mild side effects in people with metastatic castration-resistant prostate cancer (mCRPC).

开始日期2024-06-04

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

100 项与 Aurora B 相关的临床结果

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100 项与 Aurora B 相关的转化医学

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0 项与 Aurora B 相关的专利（医药）

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2,545

项与 Aurora B 相关的文献（医药）

2025-01-01·Life Science Alliance

CENP-C-Mis12 complex establishes a regulatory loop through Aurora B for chromosome segregation

Article

作者: Miao, Jiahang ; Fukagawa, Tatsuo ; Hara, Masatoshi ; Fujimori, Toshihiko ; Hirano, Yasuhiro ; Sasaki, Hiroshi ; Takenoshita, Yusuke ; Tokunaga, Yurika ; Okumura, Kazuhiro ; Wakabayashi, Yuichi ; Kong, Weixia ; Hashimoto, Masakazu

Establishing the correct kinetochore–microtubule attachment is crucial for faithful chromosome segregation. The kinetochore has various regulatory mechanisms for establishing correct bipolar attachment. However, how the regulations are coupled is not fully understood. Here, we demonstrate a regulatory loop between the kinetochore protein CENP-C and Aurora B kinase, which is critical for the error correction of kinetochore–microtubule attachment. This regulatory loop is mediated through the binding of CENP-C to the outer kinetochore Mis12 complex (Mis12C). Although the Mis12C-binding region of CENP-C is dispensable for mouse development and proliferation in human RPE-1 cells, those cells lacking this region display increased mitotic defects. The CENP-C-Mis12C interaction facilitates the centromeric recruitment of Aurora B and the mitotic error correction in human cells. Given that Aurora B reinforces the CENP-C-Mis12C interaction, our findings reveal a positive regulatory loop between Aurora B recruitment and the CENP-C-Mis12C interaction, which ensures chromosome biorientation for accurate chromosome segregation.

2024-12-31·Cancer Biology & Therapy

The effects of Aurora Kinase inhibition on thyroid cancer growth and sensitivity to MAPK-directed therapies

Article

作者: Rose, Madison M ; Nassar, Veronica L ; Lund, Jane ; Hicks, Hannah M ; Schweppe, Rebecca E

Thyroid cancer is one of the deadliest endocrine cancers, and its incidence has been increasing. While mutations in BRAF are common in thyroid cancer, advanced PTC patients currently lack therapeutic options targeting the MAPK pathway, and despite the approved combination of BRAF and MEK1/2 inhibition for BRAF-mutant ATC, resistance often occurs. Here, we assess growth and signaling responses to combined BRAF and MEK1/2 inhibition in a panel of BRAF-mutant thyroid cancer cell lines. We first showed that combined BRAF and MEK1/2 inhibition synergistically inhibits cell growth in four out of six of the -BRAF-mutant thyroid cancer cell lines tested. Western blotting showed that the MAPK pathway was robustly inhibited in all cell lines. Therefore, to identify potential mechanisms of resistance, we performed RNA-sequencing in cells sensitive or resistant to MEK1/2 inhibition. In response to MEK1/2 inhibition, we identified a downregulation of Aurora Kinase B (AURKB) in sensitive but not resistant cells. We further demonstrated that combined MEK1/2 and AURKB inhibition slowed cell growth, which was phenocopied by inhibiting AURKB and ERK1/2. Finally, we show that combined AURKB and ERK1/2 inhibition induces apoptosis in BRAF-mutant thyroid cancer cell lines, together suggesting a potential combination therapy for BRAF-mutant thyroid cancer patients.

2024-12-01·European Journal of Medicinal Chemistry

Discovery of new pyrazole-4-carboxamide analogues as potential anticancer agents targeting dual aurora kinase A and B

Review

作者: Zhang, Jie ; Huang, Tao ; Teraiya, Nishith ; Lalwani, Twinkle ; Patel, Saumya K ; Dixit, Nandan ; Patel, Saumya K. ; Mulukuri, N V L Sirisha ; Sangani, Chetan B ; Kumar, Sujeet ; Duan, Yong-Tao ; Dalasaniya, Mayur ; Sangani, Chetan B. ; Yevale, Digambar

Aurora kinases A and B are critical regulators of cell division and cytokinesis. Abnormal expression of Aurora kinases A and B causes chromosomal instability and disrupts several tumor suppressor and oncoprotein-controlled pathways. As a result, there has been a spike in interest in developing inhibitors against these kinases as anticancer treatments. This paper addresses the discovery, anticancer evaluation and druggability study of new pyrazole-4-carboxamide analogues as kinases inhibitors. Among the compounds, 6k demonstrated the highest cytotoxicity against HeLa and HepG2 cells, with IC₅₀ of 0.43 μM and 0.67 μM, respectively. It selectively inhibited Aurora kinases A and B, with IC₅₀ values of 16.3 nM and 20.2 nM, respectively, in comparison to other kinases. Molecular investigations revealed that 6k induced the inhibition of phosphorylated Thr288 (Aurora kinase A) and phosphorylated Histone H3 (Aurora kinase B), confirming its mechanism of action. Beside, compound 6k arrested the cell cycle at the G2/M phase by modulating cyclinB1 and cdc2 protein levels and increasing the Sub-G1 cell population. It also significantly increased polyploidization (>8 N) and abnormal mitosis, likely due to Aurora kinase inhibition. Furthermore, 6k boosted apoptosis through the intrinsic route, with elevated levels of p53, Bak, Bax, cleaved caspase-3, and cleaved PARP. Moreover, docking and MD simulations validated kinase inhibition-induced anticancer effects. Additionally, 6k satisfied drug-likeness parameters and remained stable in the in vitro metabolism. These findings indicate that 6k warrants further in vivo pharmacokinetic and pharmacodynamics investigations.

项与 Aurora B 相关的新闻（医药）

2024-10-30

·CPHI制药在线

晶锐医药可入脑的BET抑制剂获批临床，拥挤赛道是否还有突围机会

关注并星标CPHI制药在线近日，中国国家药监局药品审评中心（CDE）官网公示，晶锐医药1类新药JRD-018片获批临床，拟开发治疗晚期恶性肿瘤。 JRD-018是一款可入脑的BET抑制剂，今年4月已经获美国FDA批准开展1期临床研究。晶锐医药拟开启1期临床试验并将针对晚期实体瘤患者进行招募，继而扩展到血液瘤、脑转移或原发性脑瘤，旨在探索JRD-018在患者中的安全性、耐受性、药代动力学以及初步抗肿瘤活性。体内药效研究结果表明，JRD-018单独使用在脑胶质瘤模型、小细胞肺癌模型、非小细胞肺癌模型、髓性单核细胞白血病模型以及乳腺癌模型中均表现出良好的抗肿瘤活性。在临床前动物模型研究中，JRD-018已显示出良好的对脑转移或原发性脑瘤、恶性脑肿瘤的抑制效果。表观遗传学靶点之BET 溴结构域和超末端结构域（bromodomain and extra terminal domain，BET）属于溴结构域蛋白家族，BET蛋白家族包含四个异构体BRD2、BRD3、BRD4、BRDT，它们的结构相似，在N端有2个串联的溴结构域（BD1和BD2）以及一个超末端结构域（ET）。BD1和BD2识别并结合乙酰化赖氨酸残基，与染色质重塑和基因转录的调控过程相关；ET结构域与多种转录因子相互作用。BET蛋白家族通过溴结构域与乙酰化的染色质结合，从而实现在表观遗传学水平上对基因表达进行调控。 BET蛋白家族在人体内表达广泛，与多种实体瘤和恶性血液性肿瘤、炎症、肥胖、肺纤维化等多种疾病的发生和发展密切相关。如原癌基因Myc在超过一半的肿瘤中过表达，BET抑制剂通过竞争性结合阻止BRD4与染色质结合，进而抑制Myc的转录，从而实现抑制肿瘤的目的。 BET抑制剂是一类新型抗癌药，这类药物在治疗血液癌症如白血病和淋巴瘤方面具有良好的前景。BET抑制剂能够通过阻断BET蛋白的功能从而抑制肿瘤生长。研发BET蛋白选择性抑制剂是目前的新方向。目前，一系列BET抑制剂正在临床试验中检验它们治疗包括白血病、淋巴瘤、脑瘤和骨髓瘤在内的多种癌症的疗效。 BET抑制剂：诺华高调购入，加思科、正大天晴加速推进 BET被认为是抗肿瘤药物研发潜力靶点。目前，全球药企针对该靶点已开发出多款药物，详见下表。在研BET抑制剂大多为小分子化学药，此外还包括蛋白水解靶向嵌合体（PROTACs）。适应症上，BET抑制剂主要被开发用于实体瘤和血液性肿瘤，其中部分还被开发用于治疗炎症性疾病如白癜风等。全球至今还尚无BET抑制剂获批，进度最快的就是MorphoSys的Pelabresib，是首个三期临床试验取得成功的BET抑制剂。MorphoSys围绕该药物布局了骨髓纤维化、恶性外周神经鞘瘤、多发性骨髓瘤等多项适应症。 Pelabrisib是由MorphoSys AG公司研制的first-in-class BET抑制剂，近期Pelabrisib治疗骨髓纤维化III期达到了主要研究终点SVR35（脾脏缩小超过35%），从214例患者的临床数据来看， Pelabrisib与JAK抑制剂芦可替尼联用24周，有65.9%的患者脾脏缩小超过35%，而对照组（芦可替尼与安慰剂）仅有35.2%的患者达到SVR35，实验组的疗效比对照组高30.4%。今年年初，诺华以29亿美元收购MorphoSys AG从而拥有了pelabresib这款BET抑制剂。诺华将基于III期MANIFEST-2研究的积极数据在今年下半年向FDA和EMA提交pelabresib联合芦可替尼治疗骨髓纤维化的上市申请。 ZEN-3694是一种领先的差异化BET抑制剂，被开发联合免疫检查点抑制剂、PARP抑制剂、MEK抑制剂、CDK4/6抑制剂、HDAC抑制剂治疗多种肿瘤。ZEN-3694可以降低BRCA1/2和RAD51等蛋白的DNA修复活性，以提高肿瘤细胞对PARP抑制的敏感性，当前用以治疗转移性去势抵抗性前列腺癌II期临床正在开展中。2019年8月，Zenith Epigenetics 与恒翼生物就该药签订超7800万美元的许可协议，授权恒翼生物获得ZEN-3694在中国（包括中国香港、中国台湾和中国澳门地区）的权益。 JAB-8263是加科思自主研发、具有全球知识产权的小分子BET抑制剂，临床前研究显示其对多种实体瘤和血液瘤均能发挥抗肿瘤作用。从公开数据来看，JAB-8263是同类临床项目中活性最强的BET抑制剂，有望在极低剂量下有效抑制多种肿瘤生长，和Pelabrisib相比具有巨大的差异化优势。目前，加科思正在中美两地开展JAB-8263的多中心、开放性I/IIa期临床研究，适应症涉及白血病及实体瘤。 TQB3617是正大天晴自主研发的一款具有全新化学结构的BET抑制剂，能够通过抑制BET蛋白功能减少c-Myc、NF-κB、Aurora B和BCL-2等致癌基因的异常表达，进而发挥抗肿瘤作用。临床前研究结果显示，TQB3617对BET家族的BRD2、BRD3、BRD4、BRDT蛋白均具有较强的抑制活性。TQB3617用于晚期恶性肿瘤的I期临床试验显示，2例骨髓纤维化患者在治疗第12周结束时，脾脏体积较基线分别缩小13%和30%，展现出潜在的抗骨髓纤维化疗效。在28例接受疗效评估的淋巴瘤中，总缓解率（ORR）为39.3%（11/28），其中4例CR，7例PR。 Trotabresib（CC-90010）是一种新型、口服、可逆性、小分子BET抑制剂，可穿透高级别胶质瘤患者的脑肿瘤组织，临床前研究显示其可增强替莫唑胺（TMZ）的抗肿瘤作用。已公布的1b/2期开放标签、剂量探索研究结果显示：在长期随访中，新诊断胶质母细胞瘤（GBM）患者接受Trotabresib+TMZ辅助治疗或Trotabresib+TMZ+RT（放疗）同步治疗耐受性良好，未出现新的不良反应。结语整体来看，BET是进展相对较慢的一个表观遗传学药物靶点。BET蛋白家族在人体内表达广泛，与多种实体瘤和恶性血液性肿瘤、炎症、肥胖、肺纤维化等多种疾病的发生和发展密切相关，是非常有潜力的药物靶点，全球首个BET抑制剂pelabresib III期临床试验的成功宣告了该靶点的成效性，目前全球围绕BET靶点研发火热，值得一提的是，随着科学技术的发展，BET抑制剂的研发不再局限于小分子化药，已有多家企业、机构研发出BET靶向PROTACs。目前国内药企也积极布局BET靶点，而布局方式除了自主研发，还从外部企业引进，如恒翼生物。期待在药企的不懈努力下，BET靶点可以早日迎来重大突破。参考来源 1.Raajit Rampal, Sebastian Grosicki, Dominik Chraniuk et al.Updated safety and efficacy data from the phase 3 MANIFEST-2 study of pelabresib in combination with ruxolitinib for JAK inhibitor treatment-na?ve patients with myelofibrosis.?JCO?42,?6502-6502(2024).DOI:10.1200/JCO.2024.42.16_suppl.6502 2.2024 ASCO. Abstract?#6502: Updated safety and efficacy data from the phase 3 MANIFEST-2 study of pelabresib in combination with ruxolitinib for JAK inhibitor treatment-na?ve patients with myelofibrosis. END 来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床1期临床3期蛋白降解靶向嵌合体临床2期临床结果

2024-10-29

·PRNewswire

Discovery of cancer risk associations for six novel genes

REYKJAVIK, Iceland, Oct. 29, 2024 /PRNewswire/ --Scientists at deCODE genetics/Amgen, and their collaborators have discovered six novel genes with rare germline variants that associate with cancer risk. The findings are published today in Nature Genetics under the title "Gene-based burden tests of rare germline variants identify six cancer susceptibility genes". Continue Reading Kari Stefansson senior author of the paper, “Gene-based burden tests of rare germline variants identify six cancer susceptibility genes”, published today in Nature Genetics, discusses the paper with Erna V. Ivarsdottir first author on the paper. Kari Stefansson CEO of deCODE genetics and senior author on the paper in Nature Genetics, with Erna V. Ivarsdottir scientists at deCODE genetics and first author. A subset of cancers arises in individuals who are born with rare sequence variants that significantly alter their cancer risk. The discovery of such variants, like those in the BRCA1- and BRCA2 genes, has led to improved early cancer detection and the development of targeted therapies, ultimately reducing the cancer burden and improving prognosis of those carrying these mutations. In this study, the scientists analysed three large genetic datasets from individuals of European descent, including 130,991 cancer patients and 733,486 controls. Through a gene-based burden association analysis across 22 different cancer types, they found four novel genes associated with a risk of developing cancer; the pro-apoptotic BIK for prostate cancer, the autophagy involved ATG12 for colorectal cancer, TG for thyroid cancer, and CMTR2 for both lung cancer and cutaneous melanoma. The relative increase in cancer risk conferred by these variants was substantial (90-295%), but it should be noted that the design of the study does not allow accurate assessment of absolute lifetime cancer risk. Additionally, the researchers found the first genes with rare variants that are associated with a decreased risk of cancer. Specifically, loss of AURKB was found to protect against any cancer type, and loss of PPP1R15A was associated with 53% lower risk of breast cancer. This suggests that inhibition of PPP1R15A may be a therapeutic option for breast cancer. The study revealed new insight into the biological mechanisms involved in cancer predisposition that will hopefully lead to better screening and treatment strategies. Video - Photo - SOURCE deCODE genetics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2024-09-29

·精准药物

一类Aurora A-TPX2 PPI 抑制剂的发现

Aurora A是一种丝氨酸/苏氨酸蛋白激酶，在有丝分裂的早期阶段起重要作用；同时也是一个研究比较多的抗肿瘤靶点。目前报道有很多ATP口袋的竞争性激酶抑制剂 (如下图第一个)，但选择性可能会是挑战。 Aurora A与其它蛋白如TPX2、N-Myc互作发挥作用，因此破坏相应的PPI也是一种途径，而且可以期待选择性会好得多。但PPI抑制剂的研发一般认为挑战比较大。这里报道了一类Aurora A-TPX2的PPI抑制剂，并且展现出体内活性。其实在这之前，已经有这类小分子报道 (下图最后一个)，但也来自同一机构。这里主要看一个PPI抑制剂的案例，从筛选hit到优化为有体内药效的分子。PPI抑制剂也有难有易，但总体来说挑战比较大；这里这个例子看起来不算很挑战，但也不easy。分子hit是筛选来的，之前他们是用了HTS筛选了1万7 rationally selected compounds (focused library?)，这篇文章他们筛选了600个fragments，规模都不大。筛选离不开assay。fragment筛选他们用的是先TSA后ligand-based NMR，后面竞争性FP assay、co-crystal、ITC。最开始的fragment hit表现不出FP活性，也拿不到共晶。围绕hit做了简单修饰后，得到的fragment如分子2可以测得63μM活性，并拿到共晶。之后基于结构设计，逐步优化活性，最终得到后面做体内药效的分子CAM2602。其中一些SAR也比较有意思，感兴趣可以结合结构看一下。比如分子3到4，一个甲基提高了8x，文章提到这是一个rational design，通过减小羧基twist的能量penalty来提高活性。从分子2到3更是提高了50x，这里有两处改动，吲哚替换苯酚保留了氢键引入了疏水作用，右侧苯环取代的替换引起了临近Arg侧链翻转与苯环作用。总的来说是一个多重作用的结果。后面通过bioisostere替换羧酸并取得成功；之后右侧苯环引入新的取代，杂环与临近残基形成stacking及氢键，最终得到后面做药效的分子CAM2602。结合模式如下图A-C所示。正如可以预期的，这类分子表现出了非常好的激酶选择性。同时对Aurora B也有不错的选择性，如分子9可以达到1000x以上，与之前报道的选择性最好的Aurora A抑制剂相当或更好 (ATP口袋也有做到选择性上千倍的)。下图G是从结构分析对Aurora B选择性的原因。最后，in vitro及in vivo，PK and PD。总的来说CAM2602表现出良好的成药性，并展现出dose-dependent药效，虽然不及上临床的ATP口袋分子Alisertib。总的来说提供了一个PPI抑制剂从hit identification到优化至lead的案例，其中一些SAR也比较有意思。最后，如果回过头看比较早就已公布的Aurora A-TPX2肽段的复合物结构，有可能根据它就能锁定现在小分子结合的这个口袋，并评估其有一定的成药性，甚至可能in silico找到hit，virtual screening或基于structure-based modeling的design。maybe) Selective Aurora A-TPX2 Interaction Inhibitors Have In Vivo Efficacy as Targeted Antimitotic Agents, J Med Chem, 2024 声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

AACR会议临床1期临床终止临床结果