更新于：2024-06-21
Phenoxodiol
脱氢雌马酚
更新于：2024-06-21
概要
基本信息
原研机构 |
在研机构 |
最高研发阶段临床前 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评孤儿药 (美国)、孤儿药 (欧盟) |
结构
分子式C15H12O3 |
InChIKeyZZUBHVMHNVYXRR-UHFFFAOYSA-N |
CAS号81267-65-4 |
关联
19
项与 脱氢雌马酚 相关的临床试验A Dose Escalation and Dose Expansion Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma - CEP-2
A Phase 1b/2a Multicenter Study of NOX66 and External Beam Radiotherapy in Patients with Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors
A Phase 1b/2a Multicenter Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors
100 项与 脱氢雌马酚 相关的临床结果
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100 项与 脱氢雌马酚 相关的转化医学
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100 项与 脱氢雌马酚 相关的专利（医药）
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96
项与 脱氢雌马酚 相关的文献（医药）2024-02-01Journal of advanced research
ENOX2 inhibition enhances infiltration of effector memory T-cell and mediates response to chemotherapy in immune-quiescent nasopharyngeal carcinoma
Article
作者: Kam, Ngar-Woon ; Li, Xiang ; Dai, Wei ; Wu, Ka Chun ; Lee, Victor Ho-Fun ; Kwong, Dora Lai-Wan ; Hung, Desmond ; Che, Chi Ming ; Laczka, Olivier ; Tsao, Sai Wa ; Lai, Syrus Pak Hei ; Wilkinson, John
INTRODUCTION:
The immunosuppressive tumor microenvironment is a major barrier for chemotherapy. Different chemosensitization approaches to reinstate immunological surveillance for cancers that are immune quiescent at the outset, have thus been devised. Cancer-specific ENOX2 expression is correlated with abnormal cell growth and has been proposed as a cellular target for anti-cancer activity. However, the potential effects of ENOX2 on the interaction between immune system and tumor cells remain elusive.
OBJECTIVES:
To understand the mechanisms by which tumor-intrinsic ENOX2-mediated alterations in anti-tumor activity of T-cells and response to chemotherapy.
METHODS:
In situ multiplexed immunohistochemistry with single cell and bulk RNA sequencing data from nasopharyngeal carcinoma (NPC) human tissues were used to define tumor phenotypes. Two NPC cell lines, with distinct ENOX2 expression, were used in a co-culture platform to study tumor-immune interactions between cancer cells/spheroids and T-cells. The effect of cisplatin treatment with ENOX2 inhibition by idronoxil (IDX) were tested in vitro and in vivo. Multi-parametric flow cytometry was used to characterize T-cell infiltrates in an NPC tumor humanized mouse model treated with combined treatment.
RESULTS:
NPC predominantly displayed an immune-excluded profile. This "cold-phenotype" was shown to exhibit higher ENOX2 expression and was associate with poorer progression-free survival (PFS). The therapeutic combination of IDX with cisplatin was effective in promoting CD8+ effector memory T cell (Tem) differentiation and mobilization. This Tem signature was highly cytotoxic, with Tem-mediated preferential lysis of higher ENOX2-expressing NPC cells. A combination-treated humanized mouse model showing dramatic shrinkage in tumors, were intra-tumoral Tem-enriched.
CONCLUSION:
Tumor-intrinsic ENOX2 expression is associated with tumor phenotype and PFS in NPC. Targeting ENOX2 with IDX and cisplatin impose qualitative control of T-cell response by preferentially increasing immune cells infiltration, Tem differentiation and tumor suppression. We suggest that ENOX2 inhibition may be a promising therapeutic strategy to enhance the effects of chemotherapy.
2023-10-03Recent patents on anti-cancer drug discovery
Characterization of the Prognosis and Tumor Microenvironment of Cellular Senescence-related Genes through scRNA-Seq and Bulk RNA-Seq Analysis in GC.
Article
作者: Ye, Yunbin ; Wang, Yang ; Lan, Tianshu ; Chen, Shuping ; Cheng, Jiaqing ; Zhou, Zhifeng ; Guo, Guoxiang
BACKGROUND:
Cellular senescence (CS) is thought to be the primary cause of cancer development and progression. This study aimed to investigate the prognostic role and molecular subtypes of CS-associated genes in gastric cancer (GC).
METHODS:
The CellAge database was utilized to acquire CS-related genes. Expression data and clinical information of GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Patients were then grouped into distinct subtypes using the "ConsesusClusterPlus" R package based on CS-related genes. An in-depth analysis was conducted to assess the gene expression, molecular function, prognosis, gene mutation, immune infiltration, and drug resistance of each subtype. In addition, a CS-associated risk model was developed based on Cox regression analysis. The nomogram, constructed on the basis of the risk score and clinical factors, was formulated to improve the clinical application of GC patients. Finally, several candidate drugs were screened based on the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset.
RESULTS:
According to the cluster result, patients were categorized into two molecular subtypes (C1 and C2). The two subtypes revealed distinct expression levels, overall survival (OS) and clinical presentations, mutation profiles, tumor microenvironment (TME), and drug resistance. A risk model was developed by selecting eight genes from the differential expression genes (DEGs) between two molecular subtypes. Patients with GC were categorized into two risk groups, with the high-risk group exhibiting a poor prognosis, a higher TME level, and increased expression of immune checkpoints. Function enrichment results suggested that genes were enriched in DNA repaired pathway in the low-risk group. Moreover, the Tumor Immune Dysfunction and Exclusion (TIDE) analysis indicated that immunotherapy is likely to be more beneficial for patients in the low-risk group. Drug analysis results revealed that several drugs, including ML210, ML162, dasatinib, idronoxil, and temsirolimus, may contribute to the treatment of GC patients in the high-risk group. Moreover, the risk model genes presented a distinct expression in single-cell levels in the GSE150290 dataset.
CONCLUSION:
The two molecular subtypes, with their own individual OS rate, expression patterns, and immune infiltration, lay the foundation for further exploration into the GC molecular mechanism. The eight gene signatures could effectively predict the GC prognosis and can serve as reliable markers for GC patients.
2023-03-01Acta pharmacologica Sinica
SZC-6, a small-molecule activator of SIRT3, attenuates cardiac hypertrophy in mice
Article
作者: Lu, Guo-Qing ; Lu, Jing ; Wang, Pan-Xia ; Li, Ze-Yu ; Liu, Pei-Qing ; Zou, Yong ; Zhang, Xiao-Lei
Sirtuin3 (SIRT3), a class III histone deacetylase, is implicated in various cardiovascular diseases as a novel therapeutic target. SIRT3 has been proven to be cardioprotective in a model of Ang II-induced cardiac hypertrophy. However, a few small-molecule compounds targeting deacetylases could activate SIRT3. In this study, we generated a novel SIRT3 activator, 3-(2-bromo-4-hydroxyphenyl)-7-hydroxy-2H-chromen-2-one (SZC-6), through structural optimization of the first SIRT3 agonist C12. We demonstrated that SZC-6 directly bound to SIRT3 with Kd value of 15 μM, and increased SIRT3 deacetylation activity with EC50 value of 23.2 ± 3.3 µM. In neonatal rat cardiomyocytes (NRCMs), pretreatment with SZC-6 (10, 20, 40 µM) dose-dependently attenuated isoproterenol (ISO)-induced hypertrophic responses. Administration of SZC-6 (20, 40 and 60 mg·kg-1·d-1, s.c.) for 2 weeks starting from one week prior ISO treatment dose-dependently reversed ISO-induced impairment of diastolic and systolic cardiac function in wild-type mice, but not in SIRT3 knockdown mice. We showed that SZC-6 (10, 20, 40 µM) dose-dependently inhibited cardiac fibroblast proliferation and differentiation into myofibroblasts, which was abolished in SIRT3-knockdown mice. We further revealed that activation of SIRT3 by SZC-6 increased ATP production and rate of mitochondrial oxygen consumption, and reduced ROS, improving mitochondrial function in ISO-treated NRCMs. We also found that SZC-6 dose-dependently enhanced LKB1 phosphorylation, thereby promoting AMPK activation to inhibit Drp1-dependent mitochondrial fragmentation. Taken together, these results demonstrate that SZC-6 is a novel SIRT3 agonist with potential value in the treatment of cardiac hypertrophy partly through activation of the LKB1-AMPK pathway.
2
项与 脱氢雌马酚 相关的新闻（医药）2021-02-11
100 项与 脱氢雌马酚 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 |
|---|---|---|---|---|
| 输卵管癌 | 临床3期 | 美国 | 2006-10-01 | |
| 输卵管癌 | 临床3期 | 澳大利亚 | 2006-10-01 | |
| 输卵管癌 | 临床3期 | 比利时 | 2006-10-01 | |
| 输卵管癌 | 临床3期 | 意大利 | 2006-10-01 | |
| 输卵管癌 | 临床3期 | 波兰 | 2006-10-01 | |
| 输卵管癌 | 临床3期 | 西班牙 | 2006-10-01 | |
| 输卵管癌 | 临床3期 | 英国 | 2006-10-01 | |
| 铂类耐药性原发性腹膜癌 | 临床3期 | 美国 | 2006-10-01 | |
| 铂类耐药性原发性腹膜癌 | 临床3期 | 澳大利亚 | 2006-10-01 | |
| 铂类耐药性原发性腹膜癌 | 临床3期 | 比利时 | 2006-10-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1/2期 | 21 | EBRT+NOX66 (Part 1: Dose Cohort 1: NOX66 800 mg) | 繭壓遞鑰淵鹹鏇選獵淵(製夢製選積鑰觸網醖衊) = 膚願願鹽夢醖齋鏇繭憲 積醖選鑰餘齋繭齋鹹襯 (餘鏇鹹積獵製壓醖願鏇, 選顧蓋繭願衊鬱遞網獵 ~ 築鑰襯醖糧齋醖夢憲願) 更多 | - | 2024-06-18 | ||
EBRT+NOX66 (Part 1: Dose Cohort 2: NOX66 1200 mg) | 繭壓遞鑰淵鹹鏇選獵淵(製夢製選積鑰觸網醖衊) = 製製範壓鏇構糧築齋窪 積醖選鑰餘齋繭齋鹹襯 (餘鏇鹹積獵製壓醖願鏇, 選襯繭蓋築鹹壓齋襯憲 ~ 網鬱膚鹽繭艱顧遞積夢) 更多 | ||||||
临床1/2期 | 11 | nivolumab+NOX66 | 鬱選簾餘鹽憲選鏇壓餘(壓餘糧製蓋醖窪餘鑰觸) = The most common AE was local perineal irritation, readily managed with topical corticosteroid cream. 蓋構醖獵壓夢鏇衊觸構 (構餘簾蓋鹽夢範鹹積範 ) | 积极 | 2023-05-31 | ||
临床1期 | 25 | NOX66 + radiation therapy | 齋壓窪選鏇襯製鑰糧艱(醖繭鏇獵鏇顧網齋顧廠) = TEAEs considered related to NOX66 alone were mild (Grade 1) cases of dry mouth and oral mucositis; mild (Grade 1) fatigue was considered related to both NOX66 and radiation. None of the 21 Grade ≥3 TEAEs were considered related to NOX66 範鹹遞襯餘簾艱窪獵構 (網製襯蓋糧餘夢艱築糧 ) | 积极 | 2020-05-25 | ||
临床1期 | 25 | palliative radiotherapy+Veyonda | 願鹹鹽顧壓範餘範顧獵(顧顧繭鏇範壓範鏇襯積) = 鏇願糧構範簾糧鏇遞壓 憲憲廠餘遞醖夢遞淵憲 (顧廠壓艱窪鹽鬱鹽願壓 ) 更多 | 积极 | 2019-12-02 | ||
N/A | - | 窪繭襯衊築糧鹹艱艱齋(鹹築齋鬱遞壓廠襯襯衊) = Phenoxodiol also inhibited the Akt pathway by causing dephosphorylation of Akt. This inhibition of the Akt pathway inhibited expression of the apoptosis inhibitor FLIP and thus led to renal cancer apoptosis 蓋鏇顧窪鑰廠觸鑰襯廠 (鏇獵顧網鑰製觸願願齋 ) 更多 | - | 2017-04-01 | |||
临床3期 | 142 | 選獵淵襯鏇憲網築鑰鹽(窪淵憲艱蓋網淵鑰構繭) = 夢遞網餘鬱淵構壓鹹鑰 衊膚醖觸選顧餘獵壓夢 (選廠淵鹽餘齋窪鏇顧遞, 11.1 ~ 21.0) 更多 | 不佳 | 2014-01-01 | |||
Placebo + AUC2-carboplatin | 選獵淵襯鏇憲網築鑰鹽(窪淵憲艱蓋網淵鑰構繭) = 範淵艱鹹糧窪鹽願淵夢 衊膚醖觸選顧餘獵壓夢 (選廠淵鹽餘齋窪鏇顧遞, 13.1 ~ 33.4) 更多 | ||||||
临床2期 | 65 | 齋鏇顧選淵繭製觸醖齋(鏇鹹膚憲遞襯夢鹹夢膚) = 艱廠窪繭窪蓋夢襯鬱壓 襯齋築簾觸淵簾網糧廠 (鏇蓋觸鹹鹽簾範壓夢製 ) | - | 2011-05-01 | |||
齋鏇顧選淵繭製觸醖齋(鏇鹹膚憲遞襯夢鹹夢膚) = 鑰顧鏇鬱淵膚鹹蓋鹽膚 襯齋築簾觸淵簾網糧廠 (鏇蓋觸鹹鹽簾範壓夢製 ) | |||||||
临床2期 | - | (Castrate-resistant prostate cancer patients) | 製構齋淵齋顧獵顧窪齋(壓淵艱鏇鏇膚淵構膚艱) = 願醖願網齋願糧廠遞鹽 鬱鏇餘網構築構簾艱願 (廠醖積鹹壓鏇蓋鹹淵蓋 ) | - | 2010-05-20 |
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