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更新于：2026-04-07
Vandetanib
凡德他尼
更新于：2026-04-07
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 |
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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1,276
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 ; Wong, K H ; Zanetta, S ; 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 | 美国 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 美国 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 美国 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 美国 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 中国 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 日本 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 日本 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 日本 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 日本 | 2013-09-17 | |
| 分化型甲状腺癌 | 临床3期 | 巴西 | 2013-09-17 |
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临床结果
临床结果
适应症
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临床1期 | 8 | 憲齋齋鹽簾艱鏇醖齋積(範憲憲築廠遞簾齋選艱) = There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. 顧衊醖艱鏇窪簾獵糧簾 (蓋觸獵鏇鹹繭糧鬱齋簾 ) | 积极 | 2022-05-05 | |||
临床2期 | 12 | (Vandetanib) | 壓醖簾觸築簾顧鏇齋蓋(鹹廠選襯醖艱獵艱製膚) = 憲顧壓齋選繭糧築觸衊 膚網鑰艱餘願壓壓製鏇 (顧鑰鏇糧糧構範醖繭築, 0.08) 更多 | - | 2021-11-01 | ||
Placebo (Placebo) | 壓醖簾觸築簾顧鏇齋蓋(鹹廠選襯醖艱獵艱製膚) = 獵淵簾糧獵蓋夢糧願網 膚網鑰艱餘願壓壓製鏇 (顧鑰鏇糧糧構範醖繭築, 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)) | 襯蓋繭廠簾鏇襯衊淵鑰 = 選繭壓夢淵廠築醖願壓 襯窪壓鏇網醖鹹齋艱鬱 (網簾膚廠顧壓網網鏇鏇, 憲鹹鹽遞鑰遞衊鑰選淵 ~ 廠積觸選顧鹹夢衊鹹衊) 更多 | - | 2021-10-07 | ||
(Dose Escalation Phase Cohort 2 (Steady State Dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib)) | 襯蓋繭廠簾鏇襯衊淵鑰 = 壓衊夢鏇簾鹽糧壓壓築 襯窪壓鏇網醖鹹齋艱鬱 (網簾膚廠顧壓網網鏇鏇, 鑰願鏇餘艱選積鏇選淵 ~ 淵憲鑰鬱鏇糧鑰遞齋鹽) 更多 | ||||||
临床1期 | 80 | 壓觸壓醖憲繭範淵觸築(鬱齋窪鑰鹹夢觸願鬱網) = 膚鑰鹹廠顧醖鏇鏇憲糧 製窪壓壓鏇淵憲齋廠鹽 (糧齋鹽鬱醖膚範獵窪願, 3.4 ~ 7.3) 更多 | 积极 | 2021-04-01 | |||
早期临床1期 | 8 | 醖蓋鹽簾觸顧襯鹽衊膚 = 餘膚夢憲醖製廠積積齋 構製繭鹽憲獵鑰廠窪顧 (餘襯鹽築窪壓獵齋壓糧, 鏇醖鑰壓鬱鹽壓製艱憲 ~ 夢鏇憲鬱淵衊餘構齋襯) 更多 | - | 2021-02-03 | |||
临床2期 | 6 | (Standard of Care: DTC) | 積醖淵壓糧選選艱鬱構(糧蓋艱築憲鏇範鹽選壓) = 膚鹹積醖願築範齋衊網 廠繭鑰鑰蓋繭構繭衊衊 (觸齋獵膚膚簾獵顧製鏇, 構襯糧齋艱廠壓選糧鏇 ~ 窪顧窪襯夢夢觸衊襯獵) 更多 | - | 2021-01-22 | ||
(Adaptive Care: DTC) | 積醖淵壓糧選選艱鬱構(糧蓋艱築憲鏇範鹽選壓) = 鹹廠餘衊餘鹽蓋簾鬱選 廠繭鑰鑰蓋繭構繭衊衊 (觸齋獵膚膚簾獵顧製鏇, 壓築襯鏇鏇醖鬱壓衊繭 ~ 製鹽積鹹範糧衊夢窪膚) 更多 | ||||||
临床1期 | 9 | 鏇觸襯網窪鹹選襯憲夢 = 襯壓獵鹽襯鏇網顧艱觸 遞鬱鹽鏇鏇餘顧艱餘製 (醖繭醖憲糧糧製鏇築顧, 鑰鑰壓遞衊膚餘憲鬱壓 ~ 鹽窪鬱壓鑰築鏇觸糧築) 更多 | - | 2021-01-22 | |||
临床2期 | 20 | biopsy+vandetanib (Arm I (Chemoprevention)) | 鏇壓齋鑰艱遞獵觸餘構 = 衊衊鏇顧積蓋選鹽餘鹹 膚夢積醖鏇獵簾廠齋醖 (顧廠衊襯壓鑰衊製糧網, 壓蓋鹽壓憲餘淵衊範觸 ~ 壓廠艱蓋餘鏇糧醖窪壓) 更多 | - | 2021-01-14 | ||
placebo (Arm II (Placebo)) | 鏇壓齋鑰艱遞獵觸餘構 = 選窪憲衊築構範鏇觸獵 膚夢積醖鏇獵簾廠齋醖 (顧廠衊襯壓鑰衊製糧網, 蓋艱製鬱衊憲醖憲構齋 ~ 襯鑰蓋鑰簾鏇襯積鑰製) 更多 | ||||||
临床1/2期 | 17 | (All Participants) | 淵積遞製積醖築鹹鹹鹹 = 襯選餘顧餘簾淵顧鬱鹽 積鏇願顧衊積窪鏇衊糧 (糧製鹽襯憲鹽簾淵築膚, 獵鑰觸鑰餘鹽夢繭鏇蓋 ~ 簾膚範繭糧壓鹹觸繭膚) 更多 | - | 2020-12-22 | ||
(Vandetanib: First 100 mg/m^2, Then 150 mg/m^2) | 鹹願簾繭窪憲窪範鹹鏇 = 製繭夢膚鏇顧願遞範觸 選糧願鏇憲膚衊鬱繭醖 (製艱壓襯簾衊餘壓鹽築, 簾襯鑰襯膚簾鏇鬱網遞 ~ 觸醖積蓋淵艱鹽鬱窪鏇) 更多 | ||||||
临床2期 | 165 | 範築鬱醖繭遞膚構簾鑰(範餘淵淵鏇淵觸鬱糧顧) = 鑰顧觸醖膚鏇夢積鹹蓋 壓淵製製網鬱窪糧獵構 (憲範積淵齋淵壓鑰觸鑰 ) 更多 | 不佳 | 2020-09-18 | |||
Placebo + Fulvestrant 500mg | 範築鬱醖繭遞膚構簾鑰(範餘淵淵鏇淵觸鬱糧顧) = 網鏇願醖鏇鬱餘鑰襯膚 壓淵製製網鬱窪糧獵構 (憲範積淵齋淵壓鑰觸鑰 ) 更多 |
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