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更新于：2026-02-27
LY-2584702
更新于：2026-02-27
概要
基本信息
原研机构 |
在研机构- |
非在研机构 |
权益机构- |
最高研发阶段终止临床1期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C28H27F4N7O3S |
InChIKeyHDYUXDNMHBQKAU-UHFFFAOYSA-N |
CAS号1082949-68-5 |
关联
5
项与 LY-2584702 相关的临床试验NCT01372085
A Single Ascending Dose and Relative Bioavailability Study of LY2584702 in Healthy Subjects
NCT01241461
A Phase 1 Study of LY2584702 in Japanese Patients With Solid Tumors
JPRN-jRCT2080221292
A Phase 1 Study of LY2584702 in Japanese Patients with Solid Tumors
100 项与 LY-2584702 相关的临床结果
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100 项与 LY-2584702 相关的转化医学
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100 项与 LY-2584702 相关的专利（医药）
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18
项与 LY-2584702 相关的文献（医药）2025-04-15JOURNAL OF CLINICAL INVESTIGATION
LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models
Article
作者: Cohen, David A ; Rustgi, Anil K ; Sugiura, Kensuke ; De, Dechokyab ; Kariuki, Secunda W ; Klein-Szanto, Andres J ; Lengner, Christopher J ; Nishiwaki, Noriyuki ; Sims, Peter A ; Shin, Alice E ; Flashner, Samuel P ; Gabre, Joel T ; Vasan, Neil
Colorectal cancer (CRC) remains a leading cause of cancer death because of metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice. We developed genetically modified mouse models with constitutively active Pik3ca that form intestinal tumors progressing to liver metastases with an intact immune system, addressing the limitations of previous Pik3ca-mutant models, including long tumor latency, mixed histology, and lack of distant metastases. The PI3Kα-specific inhibitor alpelisib reduced migration and invasion in vitro and metastasis in vivo. We present a comprehensive analysis of vertical inhibition of the PI3K/AKT pathway in CRC using the FDA-approved drugs alpelisib and capivasertib (an AKT inhibitor) in combination with LY2584702 (a ribosomal protein S6 kinase inhibitor) in CRC cell lines and mouse- and patient-derived organoids. Tissue microarrays from patients with CRC verified that LIN28B and PI3K/AKT pathway activation correlate with CRC progression. These findings highlight the critical role of the LIN28B-mediated PI3K/AKT pathway in CRC metastasis, the therapeutic potential of targeted inhibition, and the promise of patient-derived organoids in precision medicine in metastatic CRC.
2025-02-13JOURNAL OF PHYSICAL CHEMISTRY B
In Silico Discovery of SARS-CoV-2 Main Protease Inhibitors Using Docking, Molecular Dynamics, and Fragment Molecular Orbital Calculations
Article
作者: Okamoto, Mika ; Matsumoto, Kenji ; Baba, Masanori ; Hamada, Toshiyuki ; Ishikawa, Takeshi ; Koze, Hinako ; Sudoh, Masayuki
The 3C-like protease of severe acute respiratory syndrome coronavirus 2, known as the main protease (Mpro), is an attractive drug target for the treatment of coronavirus disease 2019. This study reports the discovery of novel Mpro inhibitors using several in silico techniques, including docking, molecular dynamics (MD), and fragment molecular orbital (FMO) calculations. We performed docking calculations on 5950 compounds with bioactivity, and 12 compounds were selected. An enzymatic assay was conducted, revealing that BP-1-102 exhibits significant Mpro inhibitory activity with an IC50 of 11.1 μM. The identification of seed compounds from the experiments on a few compounds demonstrates the effectiveness of our docking calculations. Furthermore, the detailed analyses using MD and FMO calculations suggested an interaction mechanism in which the hydroxyl group of BP-1-102 forms a hydrogen bond with E166 of Mpro. The Mpro inhibitory activity of SH-4-54, a derivative without the aforementioned hydroxyl group, was investigated and observed to be significantly reduced, with an IC50 of 81.5 μM. This result strongly supports the suggested interaction mechanism.
2024-08-01Cancer research communications
Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma
Article
作者: Plas, David R ; Sarkaria, Jann N ; Behrmann, Catherine A ; Czyzyk-Krzeska, Maria F ; Qi, Xiaoyang ; Ennis, Kelli N. ; Medvedovic, Mario ; Meller, Jarek ; Reigle, James ; Sengupta, Soma ; Andreani, Cristina ; Clark, Nicholas A. ; Ennis, Kelli N ; Von Handorf, Kate M ; Scaglioni, Pier Paolo ; Clark, Nicholas A ; Von Handorf, Kate M. ; Vallabhapurapu, Subrahmanya ; Sarma, Pranjal ; Dasgupta, Biplab ; Plas, David R. ; Kendler, Ady ; Czyzyk-Krzeska, Maria F. ; Behrmann, Catherine A. ; Sarkaria, Jann N. ; Wetzel, Collin
Abstract:
Intrinsic resistance to targeted therapeutics in PTEN-deficient glioblastoma (GBM) is mediated by redundant signaling networks that sustain critical metabolic functions. Here, we demonstrate that coordinated inhibition of the ribosomal protein S6 kinase 1 (S6K1) and the receptor tyrosine kinase AXL using LY-2584702 and BMS-777607 can overcome network redundancy to reduce GBM tumor growth. This combination of S6K1 and AXL inhibition suppressed glucose flux to pyrimidine biosynthesis. Genetic inactivation studies to map the signaling network indicated that both S6K1 and S6K2 transmit growth signals in PTEN-deficient GBM. Kinome-wide ATP binding analysis in inhibitor-treated cells revealed that LY-2584702 directly inhibited S6K1, and substrate phosphorylation studies showed that BMS-777607 inactivation of upstream AXL collaborated to reduce S6K2-mediated signal transduction. Thus, combination targeting of S6K1 and AXL provides a kinase-directed therapeutic approach that circumvents signal transduction redundancy to interrupt metabolic function and reduce growth of PTEN-deficient GBM.
Significance::
Therapy for glioblastoma would be advanced by incorporating molecularly targeted kinase-directed agents, similar to standard of care strategies in other tumor types. Here, we identify a kinase targeting approach to inhibit the metabolism and growth of glioblastoma.
100 项与 LY-2584702 相关的药物交易
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外链
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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 |
|---|---|---|---|---|
| 晚期恶性实体瘤 | 临床1期 | 日本 | 2010-11-01 | |
| 转移性实体瘤 | 临床1期 | 日本 | 2010-11-01 | |
| 晚期神经内分泌肿瘤 | 临床1期 | 美国 | 2010-03-01 | |
| 晚期神经内分泌肿瘤 | 临床1期 | 法国 | 2010-03-01 | |
| 晚期肾细胞癌 | 临床1期 | 美国 | 2010-03-01 | |
| 晚期肾细胞癌 | 临床1期 | 法国 | 2010-03-01 | |
| 转移性非小细胞肺癌 | 临床1期 | 美国 | 2010-03-01 | |
| 转移性非小细胞肺癌 | 临床1期 | 法国 | 2010-03-01 | |
| 转移性肿瘤 | 临床1期 | 美国 | 2010-03-01 | |
| 转移性肿瘤 | 临床1期 | 法国 | 2010-03-01 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | 29 | 積鏇衊構憲構顧衊淵醖 = 壓繭遞憲選襯獵範鏇襯 獵觸醖範淵築艱襯築範 (製夢壓鏇繭廠膚憲窪蓋, 憲壓齋窪醖窪鹹遞繭願 ~ 願觸襯觸壓襯廠製選淵) | - | 2019-01-18 | |||
(LY2584702+Everolimus) | 積鏇衊構憲構顧衊淵醖 = 膚鬱積積鬱壓遞餘構醖 獵觸醖範淵築艱襯築範 (製夢壓鏇繭廠膚憲窪蓋, 窪醖夢壓製醖顧觸鬱壓 ~ 網選選餘構顧選鹽襯鏇) | ||||||
临床1期 | 34 | (Part A) | 艱獵淵顧遞夢構糧齋憲 = 鏇範範構窪糧夢選糧餘 壓鹹範齋選齋選糧憲膚 (簾願遞齋衊積憲積簾願, 廠窪蓋網艱衊膚憲製範 ~ 選衊淵壓蓋窪夢醖糧選) | - | 2019-01-18 | ||
(Part B) | 艱獵淵顧遞夢構糧齋憲 = 繭鏇鬱遞醖餘築憲蓋蓋 壓鹹範齋選齋選糧憲膚 (簾願遞齋衊積憲積簾願, 簾製築膚願鹹築選襯願 ~ 襯廠積鹽壓範顧觸蓋壓) | ||||||
临床1期 | 9 | (50 mg LY2584702) | 餘襯齋襯膚築艱壓選築 = 壓膚壓窪鏇憲製觸選築 齋襯獵願鑰範網鹹膚壓 (膚鹹繭獵壓醖醖壓簾積, 憲衊憲顧鏇鏇鏇糧齋糧 ~ 醖顧網衊繭網廠憲壓鏇) 更多 | - | 2018-07-16 | ||
(75 mg LY2584702) | 餘襯齋襯膚築艱壓選築 = 艱襯遞壓觸艱壓願網鬱 齋襯獵願鑰範網鹹膚壓 (膚鹹繭獵壓醖醖壓簾積, 積繭鹽糧獵艱觸願顧範 ~ 廠淵壓夢膚獵顧餘夢夢) 更多 | ||||||
临床1期 | - | 網構廠襯鑰膚鹽觸膚製(餘衊鑰願衊齋觸觸範製) = 獵夢鑰夢願膚餘齋簾鹹 鏇選膚夢蓋範遞夢製鏇 (網築鹹艱積衊夢觸齋築 ) | - | 2014-03-01 | |||
临床1期 | - | 範遞鏇醖壓遞積襯簾構(鹽簾糧壓艱醖餘蓋齋襯) = 選選觸顧憲膚築膚顧範 鬱觸廠觸積網壓製鑰鹽 (鹹壓襯構範壓襯糧鹹繭 ) | - | 2013-04-15 |
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