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更新于：2026-03-20
Vandetanib
凡德他尼
更新于：2026-03-20
概要
基本信息
药物类型 小分子化药 |
别名 N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-4-piperidinyl)methoxy)-4-quinazolinamine、N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine、Vandetanib (JAN/USAN/INN) + [18] |
作用方式 抑制剂、拮抗剂 |
作用机制 BRK抑制剂(酪氨酸蛋白激酶BRK抑制剂)、Eph抑制剂(配蛋白受体家族抑制剂)、RET抑制剂(酪氨酸蛋白激酶受体RET抑制剂) |
在研适应症 |
原研机构 |
在研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (2011-04-06), |
最高研发阶段(中国)临床3期 |
特殊审评孤儿药 (美国)、孤儿药 (日本)、孤儿药 (韩国) |
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结构/序列
分子式C22H24BrFN4O2 |
InChIKeyUHTHHESEBZOYNR-UHFFFAOYSA-N |
CAS号443913-73-3 |
关联
118
项与 凡德他尼 相关的临床试验IRCT20130313012810N51
Comparative bioequivalence study of the Vandetanib 300mg tablet manufactured by Noavaran Daroui Kimia Company vs Caprelsa ® tablets manufactured by Sanofi Pharmaceutical Company in healthy volunteers.
NCT06482086
Precision Medicine Applied to Locally Advanced Thyroid Cancer Using Tumor-derived Organoids and In-vitro Sensitivity Testing: a Phase 2a, Single-center, Open-label, and Non-comparative Study
NCT03630120
Adaptive Tyrosine Kinase Inhibitor Therapy In Patients With Advanced Progressive Thyroid Cancer
100 项与 凡德他尼 相关的临床结果
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100 项与 凡德他尼 相关的转化医学
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100 项与 凡德他尼 相关的专利（医药）
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1,184
项与 凡德他尼 相关的文献（医药）2026-05-01EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Calpain inhibition preserves myofilament integrity and prevents vandetanib–induced cardiac dysfunction
Article
作者: Huang, Jie ; Yan, Jie ; Lu, Jian ; Wu, Lin ; Lu, Lin ; Lv, Si ; Liao, Bin ; Ji, Fang ; Gu, Yinshan ; Xie, Bingbin ; Wen, Hu ; Li, Miaoling ; Yuan, Huan
Vandetanib is a novel multi-targeted tyrosine kinase inhibitor (TKI) that has demonstrated clinical efficacy in the long-term treatment of medullary thyroid carcinoma. However, its use is frequently associated with cardiovascular side effects, some of which may be life-threatening. Notably, multi-targeted TKIs have been increasingly implicated in the risk of cardiotoxicity. Among these, cardiac contractile dysfunction has emerged as a critical concern, yet the underlying mechanisms remain incompletely elucidated-particularly the phenomenon of excitation-contraction uncoupling. This study aims to investigate how vandetanib affects cardiac contractility, with a specific focus on sarcomeric protein degradation, and to identify potential molecular targets for reversing myofilament degradation. Chronic treatment with vandetanib led to a significant reduction in myocardial contractile function, the disruption of cardiac troponin T (cTnT), cardiac troponin I (cTnI) organization and downregulation of essential myofilament proteins, including cTnT (42.3% ± 5.6% protein loss)and MYOM1 (32.7% ± 4.9% protein loss), without notable suppression of calcium-handling proteins such as JPH2, p-PLN, and p-CaMKII. Calcium imaging revealed preserved sarcoplasmic reticulum (SR) calcium release, suggesting contractile dysfunction was not primarily calcium-driven. Instead, reduced myofilament calcium sensitivity and partial sarcomere disassembly were observed. Mechanistically, we identified upregulation of calpain expression and enzymatic overactivation as key mediators of sarcomeric protein degradation. Inhibition of calpain activity partially rescued vandetanib-induced loss of contractile proteins and preserved myofilament structure. Calpain1 overexpression aggravated, while calpain1 knockdown partially rescued, vandetanib-induced cTnT degradation. Our findings uncover a novel mechanism underlying TKI-induced cardiotoxicity, involving calpain-dependent degradation of cardiac myofilament proteins and independent of calcium dysregulation. This study highlights the critical role of sarcomere stability in maintaining cardiac function during TKI therapy and identifies calpain as a promising therapeutic target for cardioprotection, with calpain activation rather than calcium dysregulation being the key driver of vandetanib-induced cardiac dysfunction.
2026-03-01ESMO Open
Real-world external control arm for the single-arm LIBRETTO-001 trial of selpercatinib in RET-mutation-positive medullary thyroid cancer: RECALIB-RET
Article
作者: Schneegans, O ; Khanal, M ; Illouz, F ; Borget, I ; Benisvy, D ; Varnier, R ; Hernando, J ; Do Cao, C ; Li, X ; Buffet, C ; Zheng, S ; Nascimento, C ; Hadoux, J ; Singh, R ; Lasolle, H ; Tian, W ; Houot, B ; Segall, G ; Hescot, S ; Afonso, A S ; Muller, M ; Zanetta, S ; Wong, K H ; Drui, D ; Roudaut, N
BACKGROUND:
The single-arm phase I/II LIBRETTO-001 trial demonstrated durable efficacy with selpercatinib in patients with rearranged during transfection (RET)-mutation-positive medullary thyroid cancer (MTC). RECALIB-RET compared effectiveness outcomes using a real-world external control (EC) arm of patients with RET-mutation-positive MTC treated with standard of care (SoC) versus selpercatinib (LIBRETTO-001).
PATIENTS AND METHODS:
In this retrospective study, the selpercatinib arm comprised first-line (1L) or second-and-later-line (≥2L) patients from LIBRETTO-001. The EC arm comprised SoC-treated patients, pooled across (i) the French ENDOCAN-TUTHYREF (Refractory Thyroid Tumours) database (1L and ≥2L); (ii) a chart review of European patient medical records (1L and ≥2L) and (iii) a published United States chart review (≥2L). Index treatment was cabozantinib or vandetanib (1L) and any SoC (≥2L; including multikinase inhibitor, chemotherapy or immunotherapy). The primary endpoint was progression-free survival (PFS). The safety profile of SoC in the EC arm was a secondary endpoint. Propensity score matching (PSM) balanced baseline characteristics between treatment arms.
RESULTS:
Baseline characteristics of the 1L selpercatinib (n = 116) and EC (n = 107) arms were balanced; PSM reduced the sample size by <30% across arms (n = 84 per arm after PSM). 1L selpercatinib conferred statistically significant PFS benefit over SoC both pre-PSM [median: not reached (NR) versus 24.0 months; P < 0.001] and post-PSM (median: NR versus 26.1 months; P < 0.001). In ≥2L (selpercatinib, n = 179; EC, n = 51), PSM increased attrition, reducing sample sizes by 78.8% (selpercatinib) and 25.5% (EC), to n = 38 per arm. The unadjusted median PFS was significantly longer with ≥2L selpercatinib versus SoC (35.6 months versus 11.6 months; P = 0.005); the difference did not reach significance after PSM. Safety findings were consistent with previously reported findings for SoC.
CONCLUSION:
Selpercatinib conferred significant PFS benefit over SoC in treatment-naïve (1L) patients with RET-mutation-positive MTC, with inconclusive results in the ≥2L setting. Matching retrospective real-world data to prospective trial data is feasible. EC arms to single-arm trials may provide evidence supporting the evaluation of comparative effectiveness.
2026-02-01EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Medicinal chemistry perspective on quinazoline derivatives: Sustainable synthetic routes, anticancer evaluation, and SAR analysis
Review
作者: Dasgupta, Aryadipto ; Rajesh, R ; Paik, Arghya ; Pavani, Gajjala ; Gurubasavaraja Swamy, P M ; Dutta, Sudarshini ; Kushal, J ; Pal, Rohit
Cancer remains a leading cause of global mortality, demanding safer and more effective therapies. Quinazoline and its derivatives have gained significant interest due to their versatile biological activity and ability to modulate multiple oncogenic pathways. Among these, EGFR and VEGFR are the primary targets, with many quinazoline derivatives showing strong inhibition at nanomolar IC50 levels through hydrogen bonding and hydrophobic interactions within ATP-binding pockets. FDA-approved drugs like Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Vandetanib validate the therapeutic significance of the quinazoline framework in modulating different cancer pathways. Additionally, derivatives acting on BRAF, HER2, PARP-1, COX-2, and PI3K/Akt/mTOR pathways have shown notable cytotoxic and apoptosis-inducing effects. Different synthetic strategies, including metal-catalysed, microwave-assisted, and solvent mediated methods, have been used to develop diverse quinazoline frameworks fused with rings like triazole, thiazole, oxadiazole, and pyrimidine. Structure activity relationship (SAR) analyses reveal that adding halogen, methoxy, or heteroaryl groups at specific ring positions enhance kinase affinity and cytotoxic efficacy. Overall, this review highlights recent progress linking synthetic design, molecular docking, and biological response, establishing quinazoline derivatives as promising multitargeted scaffolds for the design of next-generation anticancer agents.
100 项与 凡德他尼 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 |
|---|---|---|---|
| RET突变阳性甲状腺髓样癌 | 欧盟 | 2023-02-01 | |
| RET突变阳性甲状腺髓样癌 | 冰岛 | 2023-02-01 | |
| RET突变阳性甲状腺髓样癌 | 列支敦士登 | 2023-02-01 | |
| RET突变阳性甲状腺髓样癌 | 挪威 | 2023-02-01 | |
| 晚期甲状腺髓样癌 | 韩国 | 2013-05-24 | |
| 转移性甲状腺髓样癌 | 韩国 | 2013-05-24 | |
| 甲状腺髓样癌 | 美国 | 2011-04-06 |
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 |
|---|---|---|---|---|
| 分化型甲状腺癌 | 临床3期 | 瑞典 | 2013-06-25 | |
| 乳头状甲状腺癌 | 临床3期 | 瑞典 | 2013-06-25 | |
| 甲状腺癌转移 | 临床3期 | 瑞典 | 2013-06-25 | |
| 滤泡型甲状腺癌 | 临床3期 | 瑞典 | 2013-06-25 | |
| 甲状腺低分化癌 | 临床3期 | 瑞典 | 2013-06-25 | |
| 非小细胞肺癌 | 临床3期 | 美国 | 2006-05-01 | |
| 非小细胞肺癌 | 临床3期 | 中国 | 2006-05-01 | |
| 非小细胞肺癌 | 临床3期 | 日本 | 2006-05-01 | |
| 非小细胞肺癌 | 临床3期 | 阿根廷 | 2006-05-01 | |
| 非小细胞肺癌 | 临床3期 | 奥地利 | 2006-05-01 |
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临床结果
临床结果
适应症
分期
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临床1期 | 8 | 鬱範壓鹹鑰衊艱積夢顧(餘鑰膚獵簾糧鑰膚網鏇) = There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. 夢築遞獵願獵膚衊艱齋 (範壓鏇膚窪鹽壓鹹構齋 ) | 积极 | 2022-05-05 | |||
临床2期 | 12 | (Vandetanib) | 壓壓選獵遞壓製鑰糧遞(醖廠範蓋蓋範艱範網願) = 鑰夢願簾鹹鏇獵膚鬱蓋 憲製網壓醖壓獵範衊獵 (糧觸鏇廠夢膚窪齋顧獵, 0.08) 更多 | - | 2021-11-01 | ||
Placebo (Placebo) | 壓壓選獵遞壓製鑰糧遞(醖廠範蓋蓋範艱範網願) = 壓鏇築觸壓艱齋廠鹹積 憲製網壓醖壓獵範衊獵 (糧觸鏇廠夢膚窪齋顧獵, 0.05) 更多 | ||||||
临床1期 | 61 | (Dose Escalation Phase Cohort 1 (Steady State Dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib)) | 壓衊觸憲襯構鑰鹽鑰廠 = 襯繭鬱夢觸醖壓網鏇鬱 製鬱鏇選鑰積鏇鑰構鬱 (廠齋齋齋繭廠窪製齋衊, 衊齋網夢醖選膚餘醖製 ~ 鹹糧網構鏇簾蓋艱膚積) 更多 | - | 2021-10-07 | ||
(Dose Escalation Phase Cohort 2 (Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib)) | 壓衊觸憲襯構鑰鹽鑰廠 = 鹹鹽廠夢窪憲壓淵蓋糧 製鬱鏇選鑰積鏇鑰構鬱 (廠齋齋齋繭廠窪製齋衊, 壓餘餘艱鏇膚範淵糧鏇 ~ 觸鑰蓋衊範願齋製顧顧) 更多 | ||||||
临床1期 | 80 | 鑰窪鬱窪鏇艱餘夢繭淵(壓艱觸鬱願鏇鹽築糧齋) = 餘選壓襯觸構顧襯醖範 製衊廠選鹹構觸夢鬱淵 (鬱蓋鏇構壓鏇襯艱觸繭, 3.4 ~ 7.3) 更多 | 积极 | 2021-04-01 | |||
早期临床1期 | 8 | 積網繭壓衊選衊簾窪觸 = 憲齋憲糧鬱鏇範簾製獵 襯膚糧廠廠餘鬱膚觸構 (獵糧鑰鹽顧鏇願廠壓醖, 鬱壓壓蓋簾鹹構糧餘襯 ~ 製壓遞艱製選範膚廠積) 更多 | - | 2021-02-03 | |||
临床2期 | 6 | (Standard of Care: DTC) | 憲膚齋獵鑰範鏇蓋醖蓋(構顧壓範願蓋醖觸壓鑰) = 廠製膚醖鏇膚鹽蓋壓衊 簾憲糧鏇膚襯淵繭襯鏇 (艱簾窪膚製鹹餘衊獵餘, 蓋獵鬱簾醖築窪襯繭餘 ~ 鏇醖遞艱衊餘壓鏇憲壓) 更多 | - | 2021-01-22 | ||
(Adaptive Care: DTC) | 憲膚齋獵鑰範鏇蓋醖蓋(構顧壓範願蓋醖觸壓鑰) = 衊範鬱襯選簾鹹齋願簾 簾憲糧鏇膚襯淵繭襯鏇 (艱簾窪膚製鹹餘衊獵餘, 繭艱淵網淵構簾鹹鹽艱 ~ 餘艱襯選築醖夢選製築) 更多 | ||||||
临床1期 | 9 | 選膚範範餘製醖壓餘獵 = 鏇膚積範壓獵製膚壓窪 壓築餘鬱構壓壓糧膚積 (構膚獵簾憲醖憲網製窪, 夢醖構鏇積鑰壓醖獵鹹 ~ 鏇夢廠鹹鹹淵構觸鏇醖) 更多 | - | 2021-01-22 | |||
临床2期 | 20 | biopsy+vandetanib (Arm I (Chemoprevention)) | 餘糧鏇簾鬱選選鹹鹽齋 = 範遞獵構積範簾壓壓遞 襯築廠獵蓋獵艱淵選構 (餘觸鹹襯範膚繭醖願窪, 鹹築範蓋遞遞積構鹹鹹 ~ 艱簾衊積窪廠窪鹽壓選) 更多 | - | 2021-01-14 | ||
placebo (Arm II (Placebo)) | 餘糧鏇簾鬱選選鹹鹽齋 = 觸鏇構構鬱餘餘鬱鏇範 襯築廠獵蓋獵艱淵選構 (餘觸鹹襯範膚繭醖願窪, 窪艱鏇夢鑰膚築襯餘遞 ~ 艱淵願艱築觸遞淵網襯) 更多 | ||||||
临床1/2期 | 17 | (All Participants) | 艱顧網獵獵顧糧艱願積 = 鹹積艱壓繭選艱膚遞膚 願鑰鏇衊鹹選窪醖衊簾 (餘齋廠淵衊淵衊構積築, 鑰願簾築鏇觸醖糧餘餘 ~ 蓋製願襯夢鬱夢繭衊顧) 更多 | - | 2020-12-22 | ||
(Vandetanib: First 100 mg/m^2, Then 150 mg/m^2) | 範壓壓蓋築範鑰網選淵 = 範網積範鬱願壓鹹觸鏇 淵餘襯積鬱觸積衊範願 (夢觸鬱夢襯夢網憲願願, 憲願淵鬱夢窪製簾簾醖 ~ 醖蓋衊膚鹹網膚築選鬱) 更多 | ||||||
临床2期 | 165 | 鏇獵窪選鹽夢壓蓋蓋蓋(糧憲選鬱鑰壓齋構願願) = 衊積觸壓鏇構觸鬱顧積 網範膚餘鹽網齋選夢顧 (窪憲遞繭選積構鑰膚蓋 ) 更多 | 不佳 | 2020-09-18 | |||
Placebo + Fulvestrant 500mg | 鏇獵窪選鹽夢壓蓋蓋蓋(糧憲選鬱鑰壓齋構願願) = 範鹹窪齋蓋繭蓋齋鹽鹽 網範膚餘鹽網齋選夢顧 (窪憲遞繭選積構鑰膚蓋 ) 更多 |
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