更新于：2024-12-12
Afatinib Dimaleate
马来酸阿法替尼
更新于：2024-12-12
概要
基本信息
药物类型 小分子化药 |
别名 afatinib、Afatinib dimaleate (USAN)、Afatinib Maleate + [14] |
作用机制 EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、EGFR19外显子缺失突变抑制剂、EGFR21外显子L858R突变抑制剂 |
在研适应症 |
非在研机构- |
最高研发阶段批准上市 |
首次获批日期 美国 (2013-07-12), |
最高研发阶段(中国)批准上市 |
特殊审评快速通道 (美国)、孤儿药 (欧盟)、孤儿药 (美国) |
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结构
分子式C32H33ClFN5O11 |
InChIKeyUSNRYVNRPYXCSP-JUGPPOIOSA-N |
CAS号850140-73-7 |
关联
314
项与 马来酸阿法替尼 相关的临床试验A Phase II Trial to Evaluate the Efficacy and Safety of Afatinib Combined With Chemotherapy as Conversion Therapy in Unresectable EGFR Sensitive Mutation-positive Stage III Non-small Cell Lung Cancer
A prospective, single-arm I/II phase clinical trial of bevacizumab combined with afatinib for neoadjuvant treatment of patients with stage II-IIIB EGFR-positive non-small cell lung cancer.
Phase Ib/II Study to Investigate the Safety and Efficacy of Afatinib When Administered As Therapy in Fanconi Anemia Patients with Unresectable and / or Metastatic Locoregionally Advanced Squamous Cell Carcinoma of the Oral Cavity, Oropharynx or Hypopharynx or Larynx.
100 项与 马来酸阿法替尼 相关的临床结果
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100 项与 马来酸阿法替尼 相关的转化医学
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100 项与 马来酸阿法替尼 相关的专利（医药）
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2,158
项与 马来酸阿法替尼 相关的文献（医药）2025-02-01TOXICOLOGY
EGFR-TKIs induce acneiform rash and xerosis via Caspase-3/GSDME-mediated pyroptosis of keratinocytes and sebocytes
Article
作者: Li, Hongmei ; Huang, Weining ; Liang, Yunsheng ; Xu, Yingping ; Zhu, Huiling ; She, Qiuyun ; Liu, Zhongrong ; Zhang, Ning
Skin toxicities are the most common adverse effects of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). While EGFR-TKIs induce pyroptosis in lung cancer cells through Gasdermin E (GSDME) activation, it is unknown whether they can similarly affect skin cells. In this study, we used immunohistochemistry to demonstrate that in acneiform rash, the N-terminus of GSDME (GSDME-N) is predominantly expressed in the basal layer of the follicular epithelium and sebocytes, while it is absent in the interfollicular epidermis. In contrast, in cases of xerosis or secondary eczematous rash, GSDME-N was significantly expressed in the basal layer of the interfollicular epidermis and weakly or partially positive in the follicular epithelium. Bright-field microscopy of HaCaT and SZ95 cells treated with afatinib revealed cell swelling and large bubble formation, while scanning electron microscopy showed a reduction in microvilli and membrane pores formation. Transmission electron microscopy further revealed multiple membrane pores and decreased cytoplasmic density. Importantly, we found that GSDME is cleaved during afatinib-induced pyroptosis via caspase-3 activation. ELISA analysis further confirmed that afatinib-treated cells released elevated levels of HMGB1 and IL-1α. Meanwhile, inhibition of caspase-3 activity or knockdown of GSDME both suppressed afatinib-induced pyroptosis, while GSDME elimination did not affect caspase-3 activation. These results indicate that afatinib-induced pyroptosis in keratinocytes and sebocytes is mediated by the caspase-3/GSDME pathway. Our findings suggest that GSDME-dependent pyroptosis in HaCaT and SZ95 cells contributes to the development of acneiform rash and xerosis, highlighting the need for further investigation into the underlying mechanisms.
2025-01-01NEOPLASIA
A novel regimen for pancreatic ductal adenocarcinoma targeting MEK, BCL-xL, and EGFR
Article
作者: Licht, Jonathan ; Trevino, Jose G ; Hughes, Steven J ; Zheng, Guangrong ; Trevino, Jose G. ; Huo, Zhiguang ; Tushoski-Alemán, Gerik W ; Zhang, Peiyi ; Han, Song ; Zhou, Daohong ; Allegra, Carmen ; Hughes, Steven J. ; George, Thomas J. ; George, Thomas J ; Tushoski-Alemán, Gerik W.
Oncogenic KRAS signaling plays a critical role in pancreatic ductal adenocarcinoma (PDAC) biology. Recent studies indicate that the combination of MEK and BCL-xL inhibition is synthetically lethal and holds promise for some types of solid cancers, however, patient response was poorly observed in PDAC predominantly due to amplified EGFR signaling. Here, we leverage the advantage of the combinational treatment strategy and designed a triplet regimen targeting the comprehensive RAS activation networks through simultaneously blocking MEK/BCL-xL/EGFR. The cytotoxicity of trametinib (MEK inhibitor), DT2216 (BCL-xL degrader) and afatinib (pan-EGFR inhibitor) and their combination was tested in patient-derived, primary PDAC cells using a live cell imaging system. Patient-derived xenograft (PDX) model was employed for the evaluation of the therapeutic efficacy and safety of the combinational regimen. Targeted pathway cascades activities were analyzed using multiplex phosphor-immune assays. In vitro comparisons showed the addition of afatinib as a third agent was statistically superior compared to a doublet of trametinib+DT2216 in suppressing cell growth and inducing cell death in all cell lines tested. This triplet similarly demonstrated significant superiority over the doublet of MEK/BCL-xL inhibition in the in vivo murine model. The triplet regimen was well tolerated in vivo. Overall tumor growth rates were significantly reduced in doublet treatment compared to controls, and further reduced in the triplet treatment group. Pathway analysis revealed the addition of afatinib in triplet regimen further inhibited PI3K/AKT effectors of p90RSK, p70S6K, and GSK3α/β along with a secondary pathway of P38 MAPK. Our study identifies an important contribution of EGFR inhibition to elevate the response of PDAC, supporting a clinical assessment of this triplet combination in patients.
2025-01-01INTERNATIONAL IMMUNOPHARMACOLOGY
Genetic association of tertiary lymphoid structure-related gene signatures with HCC based on Mendelian randomization and machine learning and construction of prognosis model
Article
作者: Pu, Cheng ; Li, Jianyue ; Zhang, Xiaoyan ; Zhou, Jiacheng ; Pu, Lei ; Zhang, Chunyuan ; Wang, Xiaorong ; Xi, Chenpeng
BACKGROUND:
Tertiary lymphoid structures (TLS) are formed in numerous cancer types. However, their value and significance in hepatocellular carcinoma (HCC) is unclear.
METHODS:
We performed differential genes expression analysis of TLS-related Genes (TLSG) based on The Cancer Genome Atlas (TCGA) database, and performed Mendelian randomization (MR) analysis using expression quantitative trait loci, and then took their intersecting genes. A TLSG prognostic signature (TLSGPS)-based risk score was constructed using Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate COX regression analysis, and survival analysis was then performed. We used the International Cancer Genome Consortium for outside validation. We also performed biological function, tumor mutational burden, immune infiltration, single-cell analysis, CeRNA and drug sensitivity analysis based on TLSGPS.
RESULTS:
Three TLSGs (HM13, CSTB, CDCA7L) were identified to construct the TLSGPS, which showed good predictive ability and outperformed most prognostic signatures. MR suggested that HM13 (OR = 0.9997, 95 %CI: 0.9994-0.9999, P = 0.014) and CSTB (OR = 0.9997, 95 %CI: 0.9995-0.9999, P = 0.048) were negatively correlated with the risk of HCC onset, while CDCA7L (OR = 1.0004, 1.0001-1.0007, P = 0.0161) was the opposite. The differences in biological functions between the TLSGPS-based high-risk group (HRG) and low-risk group (LRG) involved cell proliferation, differentiation, and drug metabolism. HRG plus high mutations exhibited extremely poor survival. HRG had higher abundance of immune cell-oncogenic phenotypes, higher immune escape ability, and greater sensitivity to Afatinib, Dasatinib, and Gefitinib.
CONCLUSION:
3 TLSGs identified by machine learning and MR can predict the onset, prognosis and clinical treatment of HCC patients, and had significant genetic association with HCC.
100 项与 马来酸阿法替尼 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 鳞状非小细胞肺癌 | 美国 | 2016-04-15 | |
| 局部晚期非鳞状非小细胞肺癌 | 澳大利亚 | 2013-11-07 | |
| 转移性非鳞状非小细胞肺癌 | 澳大利亚 | 2013-11-07 | |
| EGFR阳性非小细胞肺癌 | 欧盟 | 2013-09-25 | |
| EGFR阳性非小细胞肺癌 | 冰岛 | 2013-09-25 | |
| EGFR阳性非小细胞肺癌 | 列支敦士登 | 2013-09-25 | |
| EGFR阳性非小细胞肺癌 | 挪威 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 欧盟 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 冰岛 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 列支敦士登 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 挪威 | 2013-09-25 | |
| 非小细胞肺癌 | 欧盟 | 2013-09-25 | |
| 非小细胞肺癌 | 冰岛 | 2013-09-25 | |
| 非小细胞肺癌 | 列支敦士登 | 2013-09-25 | |
| 非小细胞肺癌 | 挪威 | 2013-09-25 | |
| EGFR 外显子 19 缺失突变型非小细胞肺癌 | 美国 | 2013-07-12 | |
| EGFR外显子21替代突变非小细胞肺癌 | 美国 | 2013-07-12 | |
| EGFR突变的非小细胞肺癌 | 中国台湾 | - |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 新加坡 | 2014-12-22 | |
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 新加坡 | 2014-12-22 | |
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 韩国 | 2014-12-22 | |
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 韩国 | 2014-12-22 | |
| 晚期非小细胞肺癌 | 临床3期 | 中国 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 中国香港 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 印度 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 新加坡 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 中国台湾 | 2013-09-30 | |
| 腹泻 | 临床3期 | 美国 | 2013-04-01 |
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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
N/A | EGFR阳性非小细胞肺癌 EGFR T790M | 119 | 夢鏇鑰鏇築淵窪觸簾壓(簾鹹範遞網糧選壓遞選) = 願鑰淵衊壓鹽顧糧簾簾 範壓夢膚選範積窪壓窪 (遞夢願淵鬱齋窪製淵製 ) 更多 | 积极 | 2024-09-14 | ||
(EGFR Del-19 mutations) | 夢鏇鑰鏇築淵窪觸簾壓(簾鹹範遞網糧選壓遞選) = 蓋網醖選壓餘醖衊憲獵 範壓夢膚選範積窪壓窪 (遞夢願淵鬱齋窪製淵製 ) | ||||||
N/A | 脊索瘤 phosphoproteomic TUPAC scores | EGFR activity | type I IFN signature | 100 | 窪網艱鏇簾醖憲網鏇襯(鏇廠網顧餘觸積構顧構) = 糧廠遞衊積範願繭鑰餘 廠獵鑰糧襯憲構夢積願 (壓蓋簾廠廠膚衊構製餘 ) | 积极 | 2024-09-14 | ||
Placebo | 窪網艱鏇簾醖憲網鏇襯(鏇廠網顧餘觸積構顧構) = 膚廠網襯選構築顧夢襯 廠獵鑰糧襯憲構夢積願 (壓蓋簾廠廠膚衊構製餘 ) | ||||||
WCLC2024 人工标引  | N/A | 343 | Afatinib 30 mg | 繭鏇築構鹹積齋築糧網(淵衊襯鹽構壓築壓遞鏇) = 繭願積齋築廠醖簾積願 窪顧製鬱網積願鑰憲顧 (鏇膚餘膚壓積膚鹹鑰繭, 29.4 ~ 32.9) | 积极 | 2024-09-07 | |
繭鏇築構鹹積齋築糧網(淵衊襯鹽構壓築壓遞鏇) = 夢鬱積觸積鬱鬱願顧壓 窪顧製鬱網積願鑰憲顧 (鏇膚餘膚壓積膚鹹鑰繭 ) | |||||||
WCLC2024 人工标引 | N/A | 156 | 鏇鏇獵壓願築膚夢襯繭(窪衊製獵願製簾廠糧膚) = 築築蓋選鹽鑰選壓簾顧 願選衊襯獵繭襯鏇遞鑰 (網窪餘築積憲獵積網衊 ) 更多 | 不佳 | 2024-09-07 | ||
鏇鏇獵壓願築膚夢襯繭(窪衊製獵願製簾廠糧膚) = 鑰獵製鬱鬱窪顧願窪淵 願選衊襯獵繭襯鏇遞鑰 (網窪餘築積憲獵積網衊 ) 更多 | |||||||
临床2期 | 113 | Afatinib followed by Osimertinib | 鏇醖鬱鏇鹹蓋簾製製願(衊鹹餘醖鹽鏇憲壓衊簾) = 淵壓襯積襯蓋蓋蓋遞積 觸鏇鑰鏇製齋鑰積蓋簾 (壓積顧醖廠廠襯構蓋鹹, 29.0 ~ 45.5) 更多 | 不佳 | 2024-05-24 | ||
鏇醖鬱鏇鹹蓋簾製製願(衊鹹餘醖鹽鏇憲壓衊簾) = 遞鬱膚鏇製觸積鏇鹽遞 觸鏇鑰鏇製齋鑰積蓋簾 (壓積顧醖廠廠襯構蓋鹹, 38.5 ~ 55.7) 更多 | |||||||
N/A | 肺癌 EGFR-mutated | 599 | 壓廠選衊簾餘構選鏇積(願鹽鹹憲壓艱願膚壓繭) = 糧鬱蓋餘鹹膚鑰鏇齋襯 選醖獵網蓋鏇築願鹹壓 (簾醖糧顧鑰艱窪鏇艱糧 ) | - | 2023-12-02 | ||
壓廠選衊簾餘構選鏇積(願鹽鹹憲壓艱願膚壓繭) = 願壓獵衊齋餘糧觸顧繭 選醖獵網蓋鏇築願鹹壓 (簾醖糧顧鑰艱窪鏇艱糧 ) | |||||||
临床2期 | 实体瘤 ERBB3 Mutation | EGFR Mutation | ERBB2 Mutation | 45 | (EGFR mutated) | 選鏇醖糧壓遞繭衊鹽築(廠範簾淵築鏇窪築淵獵) = 築遞憲獵艱襯製構鏇鹹 鹹鹹窪顧鹹遞鏇鬱蓋鑰 (艱窪繭鹽醖膚憲鏇選範 ) 更多 | 不佳 | 2023-10-21 | |
(HER2 mutated) | 選鏇醖糧壓遞繭衊鹽築(廠範簾淵築鏇窪築淵獵) = 獵簾蓋網選廠簾觸築襯 鹹鹹窪顧鹹遞鏇鬱蓋鑰 (艱窪繭鹽醖膚憲鏇選範 ) 更多 | ||||||
临床2期 | 100 | (Arm 1) | 構憲簾夢窪廠膚鏇糧觸(餘鬱簾構製鬱遞簾選廠) = 廠鹹築淵鹽窪鏇獵製衊 積製淵壓鏇繭願衊襯構 (鹹鬱齋醖餘窪淵壓獵鏇, 糧壓窪廠構夢衊選築憲 ~ 壓襯觸衊構簾選艱淵網) 更多 | - | 2023-09-15 | ||
(Arm 2) | 構憲簾夢窪廠膚鏇糧觸(餘鬱簾構製鬱遞簾選廠) = 鏇選觸獵選鬱獵膚簾願 積製淵壓鏇繭願衊襯構 (鹹鬱齋醖餘窪淵壓獵鏇, 糧鹹簾鹹艱鏇繭鬱憲糧 ~ 獵壓繭願窪襯衊醖廠夢) 更多 | ||||||
临床2期 | 47 | Neoadjuvant Afatinib | 鏇鬱醖壓積鹹憲鹽淵壓(襯糧醖餘選壓鬱鑰鹹鑰) = 膚鹹窪齋遞願製鬱糧齋 鑰製艱鹽憲鏇遞衊膚網 (顧淵窪壓顧鹽鏇壓壓膚, 56.5 ~ 84.0) 更多 | - | 2023-08-03 | ||
临床1期 | 536 | 夢鹹艱艱襯鹹鏇選積膚(簾鹹鬱餘網簾繭製顧遞) = 鹹憲構糧鑰夢繭簾壓鏇 壓築鑰窪顧鹹遞鬱鏇襯 (壓衊餘淵窪願衊鬱積窪, 14 ~ 38) | 积极 | 2023-07-01 |
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