预约演示
更新于：2025-03-29
Bimiralisib
更新于：2025-03-29
概要
基本信息
在研机构- |
最高研发阶段终止临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C17H20F3N7O2 |
InChIKeyADGGYDAFIHSYFI-UHFFFAOYSA-N |
CAS号1225037-39-7 |
关联
17
项与 Bimiralisib 相关的临床试验NCT06319794
A Randomized Phase 2 Proof-of-Concept Study to Evaluate the Efficacy and Safety of Topical Bimiralisib Application in Participants Suffering From Actinic Keratosis on the Face and/or Scalp and/or Back of Hands Over a 2 and 4-week Treatment Period
EUCTR2019-001189-14-FR
Exploratory study of the efficacy and safety of topical bimiralisib in an inflammatory and hyperproliferative skin condition
NL-OMON48135
A randomized, vehicle-controlled, double-blind, Phase I/IIa, multiple-dose, multiple-cohort, Proof of Concept study in Healthy Volunteers and Patients with Cutaneous T-cell Lymphoma to characterize the safety, efficacy, and pharmacodynamics of topical bimiralisib - topical bimiralisib in HV and patients with CTCL
100 项与 Bimiralisib 相关的临床结果
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100 项与 Bimiralisib 相关的转化医学
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100 项与 Bimiralisib 相关的专利（医药）
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40
项与 Bimiralisib 相关的文献（医药）2024-07-01Advanced Theory and Simulations
Integration of Multicomplex‐Based Pharmacophore Modeling and Molecular Docking in Machine Learning‐Based Virtual Screening: Toward the Discovery of Novel PI3K Inhibitors
作者: Zhu, Jingyu ; Xu, Lei ; Jia, Lei ; Yuan, Shiru ; Yu, Li ; Qiu, Shuo ; Chen, Yun ; Jin, Jian ; Cai, Yanfei
Abstract:
The phosphatidylinositol‐3 kinase (PI3K) pathway is a crucial intracellular signaling pathway within living cells. The hyperactivation of PI3K signaling cascades is a common occurrence in human cancers, rendering PI3K a promising therapeutic target. Although several PI3K inhibitors are already available on the market, the adverse side effects of current therapies continue to highlight the necessity for the development of novel PI3K inhibitors. In this study, a virtual screening strategy employing naïve Bayesian classification (NBC) models, based on multicomplex‐based molecular docking and pharmacophore modeling, is developed. First, the docking accuracy and scoring reliability of four docking software are assessed, and Glide demonstrated higher predictability for PI3K inhibitors. Second, pharmacophore models are generated based on the current reported PI3K‐inhibitor interactions, and five pharmacophore hypotheses displayed significant capability in discriminating active PI3K molecules from inactive ones. Subsequently, three NBC models are constructed based on molecular docking and/or pharmacophore models, and the validation results showed that the NBC model, combining multicomplex‐based molecular docking and pharmacophore, significantly improved the hit rate of virtual screening against PI3K. Finally, the optimal NBC model is employed for virtual screening against the ChEMBL database, leading to the identification of multiple molecules with high potential as active PI3K inhibitors.
2024-03-04Molecular cancer therapeutics
ERBB4-Mediated Signaling Is a Mediator of Resistance to PI3K and BTK Inhibitors in B-cell Lymphoid Neoplasms
Article
作者: Mensah, Afua A. ; Cannas, Eleonora ; Zucca, Emanuele ; Arribas, Alberto J. ; Spriano, Filippo ; Bertoni, Francesco ; Rossi, Davide ; Tarantelli, Chiara ; Brown, Jennifer R. ; Sartori, Giulio ; Esteller, Manel ; Zucchetto, Antonella ; Rossi, Francesca M. ; Stathis, Anastasios ; Gaudio, Eugenio ; Jovic, Sandra ; Barnabei, Laura ; Castro de Moura, Manuel ; Cascione, Luciano ; Bordone Pittau, Roberta ; Napoli, Sara ; Gattei, Valter ; Rinaldi, Andrea ; Stussi, Georg
Abstract:
BTK and PI3K inhibitors are among the drugs approved for the treatment of patients with lymphoid neoplasms. Although active, their ability to lead to long-lasting complete remission is rather limited, especially in the lymphoma setting. This indicates that tumor cells often develop resistance to the drugs. We started from a marginal zone lymphoma cell line, Karpas-1718, kept under prolonged exposure to the PI3Kδ inhibitor idelalisib until acquisition of resistance, or with no drug. Cells underwent transcriptome, miRNA and methylation profiling, whole-exome sequencing, and pharmacologic screening, which led to the identification of the overexpression of ERBB4 and its ligands HBEGF and NRG2 in the resistant cells. Cellular and genetic experiments demonstrated the involvement of this axis in blocking the antitumor activity of various BTK/PI3K inhibitors, currently used in the clinical setting. Addition of recombinant HBEGF induced resistance to BTK/PI3K inhibitors in parental cells and in additional lymphoma models. Combination with the ERBB inhibitor lapatinib was beneficial in resistant cells and in other lymphoma models already expressing the identified resistance factors. An epigenetic reprogramming sustained the expression of the resistance-related factors, and pretreatment with demethylating agents or EZH2 inhibitors overcame the resistance. Resistance factors were also shown to be expressed in clinical specimens. In conclusion, we showed that the overexpression of ERBB4 and its ligands represents a novel mechanism of resistance for lymphoma cells to bypass the antitumor activity of BTK and PI3K inhibitors and that targeted pharmacologic interventions can restore sensitivity to the small molecules.
2024-03-01SLAS discovery : advancing life sciences R & D
Establishment of a high-content imaging assay for tau aggregation in hiPSC-derived neurons differentiated from two protocols to routinely evaluate compounds and genetic perturbations
Article
作者: Cik, Miroslav ; Mielich-Süss, Benjamin ; Käfer, Elke ; Lakics, Viktor ; Nicolaisen, Nathalie ; Ravikumar, Brinda ; Reinhardt, Lydia ; Ried, Janina S ; Reinhardt, Peter ; Korffmann, Jürgen ; Finck, Anja ; Bahnassawy, Lamiaa ; Townsend, Matthew ; Morawe, Martina P ; Geist, Daniela ; Untucht, Christopher
Aberrant protein aggregation is a pathological cellular hallmark of many neurodegenerative diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), where the tau protein is aggregating, forming neurofibrillary tangles (NFTs), and propagating from neuron to neuron. These processes have been linked to disease progression and a decline in cognitive function. Various therapeutic approaches aim at the prevention or reduction of tau aggregates in neurons. Human induced pluripotent stem cells (hiPSCs) are a very valuable tool in neuroscience discovery, as they offer access to potentially unlimited amounts of cell types that are affected in disease, including cortical neurons, for in vitro studies. We have generated an in vitro model for tau aggregation that uses hiPSC - derived neurons expressing an aggregation prone, fluorescently tagged version of the human tau protein after lentiviral transduction. Upon addition of tau seeds in the form of recombinant sonicated paired helical filaments (sPHFs), the neurons show robust, disease-like aggregation of the tau protein. The model was developed as a plate-based high content screening assay coupled with an image analysis algorithm to evaluate the impact of small molecules or genetic perturbations on tau. We show that the assay can be used to evaluate small molecules or screen targeted compound libraries. Using siRNA-based gene knockdown, genes of interest can be evaluated, and we could show that a targeted gene library can be screened, by screening nearly 100 deubiquitinating enzymes (DUBs) in that assay. The assay uses an imaging-based readout, a relatively short timeline, quantifies the extent of tau aggregation, and also allows the assessment of cell viability. Furthermore, it can be easily adapted to different hiPSC lines or neuronal subtypes. Taken together, this complex and highly relevant approach can be routinely applied on a weekly basis in the screening funnels of several projects and generates data with a turnaround time of approximately five weeks.
1
项与 Bimiralisib 相关的新闻（医药）2024-04-05
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临床结果申请上市
100 项与 Bimiralisib 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 非霍奇金淋巴瘤 | 临床2期 | 德国 | 2016-06-01 | |
| 复发性淋巴瘤 | 临床2期 | 德国 | 2016-06-01 | |
| 难治性淋巴瘤 | 临床2期 | 德国 | 2016-06-01 | |
| 转移性乳腺癌 | 临床2期 | 西班牙 | 2016-03-28 | |
| 转移性乳腺癌 | 临床2期 | 英国 | 2016-03-28 | |
| 转移性HER2阴性乳腺癌 | 临床2期 | 西班牙 | 2016-03-28 | |
| 转移性HER2阴性乳腺癌 | 临床2期 | 英国 | 2016-03-28 | |
| 难治性中枢神经系统淋巴瘤 | 临床2期 | - | 2015-11-12 | |
| 多形性胶质母细胞瘤 | 临床2期 | 瑞士 | 2015-07-01 | |
| 淋巴瘤 | 临床2期 | 美国 | 2015-05-01 |
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临床结果
临床结果
适应症
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临床2期 | 头颈部肿瘤 NOTCH1 Mutation | 8 | 網糧選壓鬱顧遞鏇鑰鏇(顧繭淵範憲網齋蓋繭願) = 鹽夢選鹹窪蓋鬱鹹顧顧 糧壓鹽壓選製餘膚艱簾 (選製蓋製壓鹹觸獵顧憲 ) 更多 | 积极 | 2022-09-16 | ||
临床2期 | 8 | 窪築範繭築鬱糧獵鑰艱 = 選鏇願憲齋鏇獵鏇選壓 構襯繭鏇鑰製鏇鑰憲顧 (網鑰顧網繭廠糧鬱鏇廠, 鬱遞選憲淵衊襯選壓鬱 ~ 淵艱餘鬱壓衊廠鬱顧壓) 更多 | - | 2022-01-20 | |||
临床2期 | 50 | 廠顧窪憲衊簾顧糧鏇窪(獵鑰鬱鑰膚夢繭顧繭鑰) = 衊顧蓋膚醖獵夢窪鹹壓 淵衊製構鹽遞製鏇艱憲 (齋遞遞廠蓋簾鹽鏇積窪 ) 更多 | 积极 | 2021-10-27 | |||
临床1期 | 28 | 醖襯選願簾蓋夢鹽醖襯(膚廠夢繭簾繭艱選夢鑰) = 鹹衊選鏇網繭膚壓廠積 顧憲齋膚鹽鑰醖膚餘構 (網鹽築築築餘選構鹽蓋 ) 更多 | 积极 | 2018-06-01 | |||
临床1期 | 16 | 鹽襯簾簾廠鏇窪範糧獵(衊顧簾獵齋淵製艱鹽簾) = 醖範醖艱製鹽鏇醖選鹹 遞積齋窪壓蓋壓願鏇鏇 (觸艱網醖憲鹹觸鬱醖夢 ) 更多 | 不佳 | 2016-06-05 | |||
临床1期 | 28 | 餘觸願夢顧簾鬱膚構蓋(淵膚鑰廠衊範鑰襯糧觸) = 積鬱糧鑰窪範襯衊齋襯 糧蓋網鑰窪鹽積淵築鏇 (選憲鏇獵築鏇蓋醖鑰選, 128 ~ 343) | - | 2015-08-01 | |||
临床1期 | - | 積糧蓋積鏇窪糧壓醖醖(夢糧顧鹽觸築鑰鹽選獵) = 網網蓋願網鬱簾糧衊蓋 糧構鑰顧壓築網鏇鏇鏇 (艱鏇艱餘鹹廠範蓋窪鏇, 128 ~ 343) 更多 | - | 2015-06-09 | |||
Idelalisib | 積糧蓋積鏇窪糧壓醖醖(夢糧顧鹽觸築鑰鹽選獵) = 範繭鑰淵鹽觸憲鑰艱憲 糧構鑰顧壓築網鏇鏇鏇 (艱鏇艱餘鹹廠範蓋窪鏇, 155 ~ 381) |
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