预约演示
更新于：2026-06-24
Velzatinib
更新于：2026-06-24
概要
基本信息
药物类型 小分子化药 |
别名 [4-(Methyl-1H-pyrazol-4-yl)-benzyl]-(6[7-(3-pyrrolidin-1-yl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-4-yl]-amine、GSK'981、GSK 6042981 + [8] |
作用方式 抑制剂 |
作用机制 TYK2抑制剂(酪氨酸蛋白激酶TYK2抑制剂)、c-Kit抑制剂(干细胞生长因子受体抑制剂) |
在研适应症 |
非在研适应症- |
原研机构 |
非在研机构 |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)临床3期 |
特殊审评快速通道 (美国)、孤儿药 (美国)、孤儿药 (欧盟) |
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结构/序列
分子式C29H32N8O |
InChIKeyLVMAULGVWBINFP-UHFFFAOYSA-N |
CAS号2590556-80-0 |
关联
3
项与 Velzatinib 相关的临床试验NCT07585266
A Phase 3, Randomized, Multicenter, Open-Label Study of Velzatinib (GSK6042981) Versus Imatinib in Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST)
NCT07218926
A Phase 3, Randomized, Multicenter, Open-Label Study of IDRX-42 (GSK6042981) Versus Sunitinib in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) After Imatinib Therapy (StrateGIST 3)
NCT05489237
A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST 1]
100 项与 Velzatinib 相关的临床结果
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100 项与 Velzatinib 相关的转化医学
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100 项与 Velzatinib 相关的专利（医药）
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4
项与 Velzatinib 相关的文献（医药）2025-07-02MOLECULAR CANCER THERAPEUTICS
M4205 (IDRX-42) Is a Highly Selective and Potent Inhibitor of Relevant Oncogenic Driver and Resistance Variants of KIT in Cancer
Article
作者: Grädler, Ulrich ; Dorsch, Dieter ; Ross, Edith ; Petersson, Carl ; Leuthner, Birgitta ; Sherbetjian, Eva ; Blum, Andreas ; Drechsler, Christine ; Linde, Nina ; Blaukat, Andree ; Esdar, Christina ; Schieferstein, Hanno
Abstract:
Primary activating mutations in KIT (exon 9/11) are key driver alterations in about 80% of gastrointestinal stromal tumors (GIST). Imatinib, a small-molecule tyrosine kinase inhibitor, is used successfully as first-line therapy for patients with unresectable metastatic or recurrent GIST, but secondary resistance mutations in the KIT kinase domains frequently occur. Currently approved later-line therapies target these mutations incompletely with limited clinical benefit. M4205, a kinome-selective KIT inhibitor, was designed to address this high unmet medical need by inhibiting all relevant KIT driver and resistance mutations. Compared with imatinib, M4205 shows stronger antitumor activity in preclinical GIST models driven by oncogenic KIT driver mutations. M4205 demonstrates clinically relevant efficacy in a range of preclinical GIST models expressing different secondary KIT resistance mutations. The kinase selectivity profile of M4205 is superior to the registered standard of care and investigational agents. M4205, now IDRX-42, is currently being investigated in a phase I first-in-human study in participants with GIST.
2023-08-01Clinical cancer research : an official journal of the American Association for Cancer Research
Antitumor Efficacy of the Novel KIT Inhibitor IDRX-42 (Formerly M4205) in Patient- and Cell Line–Derived Xenograft Models of Gastrointestinal Stromal Tumor (GIST)
Article
作者: Schöffski, Patrick ; Verreet, Jasper ; Wozniak, Agnieszka ; Esdar, Christina ; De Sutter, Luna ; Sciot, Raf ; Linde, Nina ; Drechsler, Christine ; Vanleeuw, Ulla ; De Cock, Lore
Abstract:
Purpose::
The majority of gastrointestinal stromal tumors (GIST) are driven by constitutively activated KIT/PDGFRA kinases and are susceptible to treatment with tyrosine kinase inhibitors. During treatment, most of these tumors will develop secondary mutations in KIT or PDGFRA inducing drug resistance, so there is an unmet need for novel therapies. We tested the efficacy of IDRX-42, a novel selective KIT inhibitor with high activity toward the most relevant KIT mutations, in 4 GIST xenograft models.
Experimental Design::
NMRI nu/nu mice were transplanted with patient-derived GIST xenograft models UZLX-GIST9 (KIT:p.P577del;W557LfsX5;D820G), UZLX-GIST2B (KIT:p.A502_Y503dup), UZLX-GIST25 (KIT:p.K642E), and the cell line–derived model GIST882 (KIT:p.K642E). Mice were treated daily with vehicle (control), imatinib (100 mg/kg), sunitinib (20 mg/kg), avapritinib (5 mg/kg), or IDRX-42 (10 mg/kg, 25 mg/kg). Efficacy was assessed by tumor volume evolution, histopathology, grading of histologic response, and IHC. The Kruskal–Wallis and Wilcoxon matched-pairs tests were used for statistical analysis, with P < 0.05 considered as significant.
Results::
IDRX-42 (25 mg/kg) caused tumor volume shrinkage in UZLX-GIST25, GIST882, and UZLX-GIST2B, with a relative decrease to 45.6%, 57.3%, and 35.1% on the last day as compared with baseline, and tumor growth delay (160.9%) compared with control in UZLX-GIST9. Compared with controls, IDRX-42 (25 mg/kg) induced a significant decrease in mitosis. In UZLX-GIST25 and GIST882 grade 2–4 histologic response with myxoid degeneration was observed in all IDRX-42 (25 mg/kg)-treated tumors.
Conclusions::
IDRX-42 showed significant antitumor activity in patient- and cell line–derived GIST xenograft models. The novel kinase inhibitor induced volumetric responses, decreased mitotic activity, and had antiproliferative effects. In models with KIT exon 13 mutation IDRX-42 induced characteristic myxoid degeneration.
2023-02-23Journal of medicinal chemistry1区 · 医学
Identification of M4205─A Highly Selective Inhibitor of KIT Mutations for Treatment of Unresectable Metastatic or Recurrent Gastrointestinal Stromal Tumors
1区 · 医学
Article
作者: Linde, Nina ; Blum, Andreas ; Glaser, Nina ; Brandstetter, Susanne ; Dorsch, Dieter ; Ruff, Aaron ; Petersson, Carl ; Busch, Michael ; Sherbetjian, Eva ; Buchstaller, Hans-Peter ; Esdar, Christina ; Grädler, Ulrich ; Schieferstein, Hanno
The treatment of gastrointestinal stromal tumors (GISTs) driven by activating mutations in the KIT gene is a prime example of targeted therapy for treatment of cancer. The approval of the tyrosine kinase inhibitor imatinib has significantly improved patient survival, but emerging resistance under treatment and relapse is observed. Several additional KIT inhibitors have been approved; still, there is a high unmet need for KIT inhibitors with high selectivity and broad coverage of all clinically relevant KIT mutants. An imidazopyridine hit featuring excellent kinase selectivity was identified in a high-throughput screen (HTS) and optimized to the clinical candidate M4205 (IDRX-42). This molecule has a superior profile compared to approved drugs, suggesting a best-in-class potential for recurrent and metastatic GISTs driven by KIT mutations.
100 项与 Velzatinib 相关的药物交易
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研发状态
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 |
|---|---|---|---|---|
| 转移性胃肠道间质瘤 | 临床3期 | - | 2026-06-15 | |
| 胃肠道间质瘤 | 临床3期 | 澳大利亚 | 2025-12-03 | |
| 胃肠道间质瘤 | 临床3期 | 比利时 | 2025-12-03 | |
| 胃肠道间质瘤 | 临床3期 | 巴西 | 2025-12-03 | |
| 胃肠道间质瘤 | 临床3期 | 加拿大 | 2025-12-03 | |
| 胃肠道间质瘤 | 临床3期 | 法国 | 2025-12-03 | |
| 胃肠道间质瘤 | 临床3期 | 德国 | 2025-12-03 | |
| 不可切除的胃肠道间质瘤 | 临床3期 | 美国 | 2025-12-03 | |
| 不可切除的胃肠道间质瘤 | 临床3期 | 中国 | 2025-12-03 | |
| 不可切除的胃肠道间质瘤 | 临床3期 | 日本 | 2025-12-03 |
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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期 | 胃肠道间质瘤 KIT Mutation | 89 | 淵壓齋選積遞觸窪積鹽(範繭膚糧蓋顧壓餘齋選) = 獵範範壓醖鬱觸範醖窪 廠選糧壓鹹範範膚齋鹽 (繭糧艱衊願餘獵願鑰窪 ) 更多 | 积极 | 2024-11-14 | ||
(second-line) | 淵壓齋選積遞觸窪積鹽(範繭膚糧蓋顧壓餘齋選) = 艱遞衊膚憲願願獵鹹鏇 廠選糧壓鹹範範膚齋鹽 (繭糧艱衊願餘獵願鑰窪 ) 更多 | ||||||
临床1期 | 胃肠道间质瘤 KIT Mutation | 73 | 夢鑰構窪鬱繭壓顧構糧(構獵糧艱衊簾範繭窪獵) = 網壓艱鹹製膚壓簾願鏇 蓋壓鹽願餘築醖構餘範 (觸艱膚範襯艱衊齋憲顧 ) 更多 | 积极 | 2024-07-03 | ||
临床1期 | 42 | 觸鏇糧鑰淵觸廠構糧鹽(鹽選鹽蓋淵製顧衊糧窪) = 餘衊齋淵糧遞鹽顧餘鏇 壓糧壓獵簾積艱齋蓋製 (壓構窪築鹽蓋齋壓衊觸 ) 更多 | 积极 | 2024-05-24 | |||
觸鏇糧鑰淵觸廠構糧鹽(鹽選鹽蓋淵製顧衊糧窪) = 簾衊襯築築顧齋顧衊衊 壓糧壓獵簾積艱齋蓋製 (壓構窪築鹽蓋齋壓衊觸 ) 更多 | |||||||
临床1期 | 胃肠道间质瘤 KIT Mutation | 33 | 觸淵網蓋醖醖糧鹹鬱齋(襯膚夢鬱壓廠淵範繭廠) = NR 遞膚鹹繭夢鹹範醖糧鬱 (願廠憲鑰鏇鹽壓鬱窪衊 ) 更多 | 积极 | 2023-11-02 |
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