预约演示
更新于：2025-11-14
Valemetostat Tosilate
伐美妥司他
更新于：2025-11-14
概要
基本信息
药物类型 小分子化药 |
别名 valemetostat tosilate、valemetostat tosylate、甲苯磺酸伐美妥司他 + [6] |
作用方式 抑制剂 |
作用机制 EZH1抑制剂(Zeste基因增强子同源物1抑制剂)、EZH2抑制剂(组蛋白赖氨酸甲基化酶EZH2抑制剂)、表观遗传学药物 |
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 日本 (2022-09-26), |
最高研发阶段(中国)临床1/2期 |
特殊审评孤儿药 (美国)、孤儿药 (欧盟)、孤儿药 (日本) |
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结构/序列
分子式C33H42ClN3O7S |
InChIKeyJSBKGJUYSLVFPF-WJQUPPJOSA-N |
CAS号1809336-93-3 |
关联
21
项与 伐美妥司他 相关的临床试验NCT06294548
A Phase Ib/II, Dose Escalation and Dose Expansion Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma (HCC)
NCT05879484
A Phase Ib/II Multicenter Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Metastatic Squamous Cell Carcinoma (SCC) of the Head and Neck: The PANTHERAS
NCT06632977
PREcision DIagnostics in Prostate Cancer Treatment (PREDICT)
100 项与 伐美妥司他 相关的临床结果
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100 项与 伐美妥司他 相关的转化医学
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100 项与 伐美妥司他 相关的专利（医药）
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64
项与 伐美妥司他 相关的文献（医药）2025-12-01FUNCTIONAL & INTEGRATIVE GENOMICS
Polycomb repressive complex 2 (PRC2) pathway’s role in cancer cell plasticity and drug resistance
Review
作者: Tabari, Mohammad Amin Khazeei ; Khan, Haroon ; Javan, Alireza ; Larsen, Danaé S ; Rezaee, Aryan ; Heidari, Mohammad Mahdi ; Sanaye, Pantea Majma ; Hadipour, Mahboube ; Goleij, Pouya ; Daglia, Maria
Polycomb Repressive Complex 2 (PRC2) is a central regulator of gene expression via the trimethylation of histone H3 on lysine 27. This epigenetic modification plays a crucial role in maintaining cell identity and controlling differentiation, while its dysregulation is closely linked to cancer progression. PRC2 silences tumor suppressor genes, promoting cell proliferation, metastasis, epithelial-mesenchymal transition, and cancer stem cell plasticity. Enhancement of zeste homolog 2 (EZH2) overexpression or gain-of-function mutations have been observed in several cancers, including lymphoma, breast, and prostate cancers, driving aggressive tumor behavior and drug resistance. In addition to EZH2, other PRC2 components, such as embryonic ectoderm development (EED) and suppressor of zeste 12, are essential for complex stability and function. EED, in particular, enhances EZH2 activity and has emerged as a therapeutic target. Inhibitors like MAK683 and EED226 disrupt EED's ability to maintain PRC2 activity, thereby reducing H3K27me3 levels and reactivating tumor suppressor genes. Valemetostat, a dual inhibitor of both EZH2 and EED, has shown promising results in aggressive cancers like diffuse large B-cell lymphoma and small-cell lung cancer, underlining the therapeutic potential of targeting multiple PRC2 components. PRC2's role extends beyond gene repression, as it contributes to metabolic reprogramming in tumors, regulating glycolysis and lipid synthesis to fuel cancer growth. Furthermore, PRC2 is implicated in chemoresistance, particularly by modulating DNA damage response and immune evasion. Tazemetostat, a selective EZH2 inhibitor, has demonstrated significant clinical efficacy in EZH2-mutant cancers, such as non-Hodgkin lymphomas and epithelioid sarcoma. However, the compensatory function of enhancer of zeste homolog 1 (EZH1) in some cancers requires dual inhibition strategies, as seen with agents like UNC1999 and Tulmimetostat, which target both EZH1 and EZH2. Given PRC2's multifaceted role in cancer biology, its inhibition represents a promising avenue for therapeutic intervention. The continued development of PRC2 inhibitors and exploration of their use in combination with standard chemotherapy or immunotherapy has great potential for improving patient outcomes in cancers driven by PRC2 dysregulation.
2025-12-01CANCER CHEMOTHERAPY AND PHARMACOLOGY
Pharmacokinetics, metabolism, and excretion of [14C]-valemetostat in healthy male participants, and in vitro plasma protein binding
Article
作者: Siebers, Nicholas ; Inaba, Shinichi ; Craveiro, Thuy Vu ; Ikeda, Tomoko ; Kazui, Miho ; Shimizu, Takako ; Tachibana, Masaya ; Abutarif, Malaz A
INTRODUCTION:
Valemetostat tosylate (valemetostat) is an oral, selective, dual inhibitor of enhancer of zeste homolog (EZH)2 and EZH1. This article reports findings on the mass balance and pharmacokinetics of valemetostat in a phase I study; valemetostat metabolite identification in plasma, urine, and fecal samples; and plasma-protein-binding of valemetostat in vitro.
METHODS:
Eight healthy participants received a single 200-mg oral dose of [14C]-valemetostat under fasting conditions. Blood, urine, and feces samples were collected to determine total radioactivity and/or unchanged valemetostat, and for metabolite identification. The binding of valemetostat 600-10,000 ng/mL to plasma, 4% human serum albumin (HSA), and 0.1% alpha-1-acid glycoprotein (AAG) was assessed in vitro.
RESULTS:
Mean cumulative recovery of administered radioactivity was 95.3% by 360 h post-dose, with a mean recovery of 15.6% in urine and 79.8% in feces. Valemetostat accounted for the most radioactivity in the excreta, at 10% and 64.9% of the administered dose in the urine and feces, respectively. CALZ-1809a was the most abundant metabolite, present in all biological samples, and accounted for 5.6% of total radioactivity in the feces. Valemetostat was minimally associated with red blood cells, with a blood-to-plasma total radioactivity ratio of 0.54. In vitro, valemetostat was highly plasma-bound (> 94%) at clinically relevant concentrations, with a higher affinity to AAG than to HSA.
CONCLUSION:
Valemetostat was rapidly absorbed into the systemic circulation, mainly excreted via the biliary/fecal route, primarily metabolized by CYP3A enzymes to CALZ-1809a, and highly bound to plasma proteins, with a greater affinity to AAG than HSA in vitro.
2025-11-01CTS-Clinical and Translational Science
Effect of Valemetostat on the Pharmacokinetics of Midazolam and Digoxin: A Phase 1 Drug–Drug Interaction Study in Patients With Non‐Hodgkin Lymphoma
Article
ABSTRACT:
Valemetostat tosylate (valemetostat) is an oral, potent, dual inhibitor of enhancer of zeste homolog (EZH)2/1, under investigation in non‐Hodgkin lymphomas (NHLs) and solid tumors. In vitro, it inhibits cytochrome P450 3A (CYP3A) and P‐glycoprotein (P‐gp) when combined with sensitive CYP3A or P‐gp substrates. This drug–drug interaction (DDI) sub‐study is part of the phase 1 trial of valemetostat monotherapy (DS3201‐A‐J101; NCT02732275), assessing the effect of valemetostat on the pharmacokinetics (PK) of sensitive CYP3A and P‐gp substrates midazolam and digoxin, respectively, in patients with relapsed or refractory NHL, and its safety and efficacy. Patients received two simultaneous single doses of midazolam and digoxin: once alone and once concomitantly with a daily 200 mg valemetostat dose in a 28‐day cycle. Of 24 enrolled patients, 15 and 16 were evaluable for PK analyses of midazolam and digoxin, respectively. Valemetostat co‐administration caused a slight decrease in midazolam maximum plasma concentration (
Cmax
) (geometric least‐squares mean ratio [GMR], 0.966 [90% confidence interval (CI), 0.769–1.21]) and area under the plasma concentration–time curve up to the last quantifiable time (AUC
last
) (GMR, 0.87 [90% CI, 0.75–1.03]), increased digoxin
Cmax
(GMR, 1.30 [90% CI, 1.07–1.57]), and AUC
last
(GMR, 1.27 [90% CI, 1.06–1.52]). The overall safety and efficacy outcomes were similar to other studies. Valemetostat showed a manageable and tolerable safety profile, without clinically meaningful DDI with sensitive CYP3A substrates. Co‐administration of valemetostat and P‐gp substrates with a narrow therapeutic index may require careful monitoring and/or DDI risk management.
46
项与 伐美妥司他 相关的新闻（医药）2025-11-11
·医路我伴
上市批准抗体药物偶联物免疫疗法
2025-11-09
·信狐药迅
申请上市临床申请
2025-11-08
·药事纵横
抗体药物偶联物财报细胞疗法免疫疗法临床3期
100 项与 伐美妥司他 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 |
|---|---|---|---|
| 成人T细胞白血病/淋巴瘤 | 日本 | 2022-09-26 | |
| 外周T细胞淋巴瘤 | 日本 | 2022-09-26 |
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 |
|---|---|---|---|---|
| 转移性非小细胞肺癌 | 临床2期 | 美国 | 2024-10-30 | |
| 转移性非小细胞肺癌 | 临床2期 | 中国 | 2024-10-30 | |
| 转移性非小细胞肺癌 | 临床2期 | 日本 | 2024-10-30 | |
| 转移性非小细胞肺癌 | 临床2期 | 阿根廷 | 2024-10-30 | |
| 转移性非小细胞肺癌 | 临床2期 | 巴西 | 2024-10-30 | |
| 转移性非小细胞肺癌 | 临床2期 | 韩国 | 2024-10-30 | |
| 鳞状非小细胞肺癌 | 临床2期 | 美国 | 2024-10-30 | |
| 鳞状非小细胞肺癌 | 临床2期 | 中国 | 2024-10-30 | |
| 鳞状非小细胞肺癌 | 临床2期 | 日本 | 2024-10-30 | |
| 鳞状非小细胞肺癌 | 临床2期 | 阿根廷 | 2024-10-30 |
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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 | 22 | 衊壓簾選顧廠鏇獵築艱(廠獵夢遞窪鹽餘鹹製簾) = no Vale MTD has been identified up to 200 mg 築鬱製醖顧鹹艱糧簾築 (鑰衊壓憲膚築醖遞艱窪 ) | 积极 | 2025-10-17 | |||
临床1期 | 65 | (metastatic clear cell renal cell carcinoma) | 廠廠顧蓋廠繭艱選糧糧(鬱膚願構窪醖鬱鹽繭醖) = 鬱襯願遞鏇選衊網築觸 積遞範鬱繭鏇餘網選鹹 (鹹廠網衊鏇糧襯艱鏇鹽 ) 更多 | 积极 | 2025-10-17 | ||
(aggressive variant prostate cancer) | 願鑰蓋遞顧壓衊鬱衊構(憲窪製廠構廠獵範築襯) = 鹽蓋製襯積襯齋窪窪鏇 獵淵餘蓋獵願獵積鏇製 (鹹獵簾顧齋衊膚夢築製 ) 更多 | ||||||
临床1期 | 实体瘤 INI1-negative | 30 | 觸壓築憲醖構鹹鑰淵選(繭壓製製糧糧繭選糧窪) = One patient with NB developed acute lymphocytic leukemia as a secondary malignancy 壓醖廠繭衊廠顧顧憲選 (築齋選衊蓋餘憲鹹製鏇 ) 更多 | 积极 | 2025-05-30 | ||
临床2期 | 成人T细胞白血病/淋巴瘤 HTLV-1 | - | 廠鬱淵憲鏇鏇艱顧鬱鬱(餘構獵鑰網觸構齋願糧) = 顧餘鹽顧鑰構顧蓋積糧 襯鏇鑰鹹構鹹鏇醖夢糧 (網網範網獵襯襯範餘廠 ) | - | 2025-04-29 | ||
临床2期 | - | Valemetostat tosylate (valemetostat) 200 mg per day | 衊齋鹹壓廠蓋顧糧齋鬱(繭鏇鏇醖積衊醖繭衊鑰) = 廠淵壓構獵膚憲齋淵製 廠鏇選衊獵蓋齋築衊獵 (築糧醖醖淵醖鹹艱積範, 35 ~ 53) | 积极 | 2024-12-01 | ||
临床2期 | 155 | 範簾簾願構顧醖構憲鹽 = 構糧鬱蓋艱顧網醖糧壓 衊遞鏇鹽糧顧鹹築衊衊 (鏇鏇壓網醖齋糧襯鏇願, 夢窪遞製積範構繭鑰餘 ~ 遞遞構窪蓋範糧憲顧餘) 更多 | - | 2024-07-22 | |||
临床1期 | 非霍奇金淋巴瘤 EZH2 mutation | 90 | valemetostat tosylate 150-300 mg/d | 夢廠膚構淵襯製簾鬱獵(夢糧齋鹹繭鬱鬱網壓選) = 獵願餘淵網膚憲遞簾夢 鹽窪鏇鬱鏇壓窪鏇衊製 (齋獵簾獵壓淵構衊餘選 ) 更多 | 积极 | 2024-05-14 | |
(ATLL) | 醖願壓廠鑰願膚蓋網蓋(蓋遞積鹽鹹餘膚鹹夢簾) = 鏇鏇壓製築顧鹹糧觸鹹 淵鬱積繭餘壓餘糧構簾 (壓淵鹽選鹽網醖醖餘夢, 1.4 ~ 38.7) 更多 | ||||||
临床2期 | 119 | (pts with 1 prior LOT) | 鹹繭鹽齋鹹衊願襯膚簾(顧夢廠艱範範簾範鑰鹹) = 壓繭膚衊鑰襯窪鏇鹽鑰 範觸鬱餘積選壓觸構鏇 (淵選鹹範衊膚襯餘膚衊, 35.5 ~ 69.6) | 积极 | 2024-05-14 | ||
(pts with 2 prior LOT) | 鹹繭鹽齋鹹衊願襯膚簾(顧夢廠艱範範簾範鑰鹹) = 獵艱繭夢齋艱觸網艱夢 範觸鬱餘積選壓觸構鏇 (淵選鹹範衊膚襯餘膚衊, 28.3 ~ 65.7) | ||||||
临床1期 | 28 | (DS-3201b 150 mg) | 願鹽構蓋艱簾顧鏇築鬱 = 鹹製憲積鹽範顧壓鑰範 夢鑰艱衊鬱鹽餘選憲膚 (憲夢鬱鏇製襯積鬱鹹艱, 繭壓鹹醖壓窪衊膚夢窪 ~ 餘簾餘鹽構淵顧築艱壓) 更多 | - | 2024-01-30 | ||
(DS-3201b 250 mg) | 願鹽構蓋艱簾顧鏇築鬱 = 顧鏇選網淵襯製遞選壓 夢鑰艱衊鬱鹽餘選憲膚 (憲夢鬱鏇製襯積鬱鹹艱, 築簾繭願鑰鬱製餘淵範 ~ 艱醖憲製醖鏇網願獵窪) 更多 | ||||||
临床1期 | 71 | 簾醖鑰蓋製築構蓋願糧(簾鏇艱蓋選觸觸餘膚構) = 構鹽衊窪繭鹹製鑰獵範 衊獵衊鹽膚鹹構醖餘壓 (壓襯選選構構積築壓顧 ) 更多 | - | 2023-12-09 |
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