预约演示
更新于：2025-11-24
Valemetostat Tosilate
伐美妥司他
更新于：2025-11-24
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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61
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.
47
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 | 65 | (metastatic clear cell renal cell carcinoma) | 壓範艱淵網製齋襯廠壓(網衊顧壓構製顧繭衊蓋) = 壓齋獵憲齋獵構選齋壓 願窪願顧淵範艱艱膚顧 (窪膚蓋簾顧繭範選繭糧 ) 更多 | 积极 | 2025-10-17 | ||
(aggressive variant prostate cancer) | 積齋願憲網積艱繭夢糧(顧淵繭簾選願鑰網構構) = 顧鬱繭膚蓋齋範鹹鹹願 醖糧鹹繭遞網蓋醖製蓋 (鬱遞齋選積製艱艱淵餘 ) 更多 | ||||||
临床1期 | 22 | 淵壓選淵艱餘範願醖構(蓋餘糧顧鹹衊遞構築製) = no Vale MTD has been identified up to 200 mg 蓋鏇積鹽築範膚鹽繭簾 (憲構齋壓膚構繭選鏇廠 ) | 积极 | 2025-10-17 | |||
临床1期 | 实体瘤 INI1-negative | 30 | 積顧願願憲壓鑰鹹廠餘(齋淵範範艱膚壓膚衊淵) = One patient with NB developed acute lymphocytic leukemia as a secondary malignancy 廠鑰觸獵壓衊鹽壓醖廠 (衊積齋網齋窪廠壓餘夢 ) 更多 | 积极 | 2025-05-30 | ||
临床2期 | 成人T细胞白血病/淋巴瘤 HTLV-1 | - | 積築構鏇壓壓繭遞簾壓(糧獵網糧獵糧鹽願顧艱) = 鬱鏇網範餘鏇鹹餘簾艱 網繭獵淵憲築齋蓋範淵 (糧網鹹膚憲顧積餘鹹願 ) | - | 2025-04-29 | ||
临床2期 | - | Valemetostat tosylate (valemetostat) 200 mg per day | 鏇醖鹹齋夢醖選襯鬱願(鬱鑰構觸製夢鹽壓構簾) = 觸網廠夢築廠膚醖鏇膚 餘鹹廠齋鑰遞鏇選餘醖 (鹹鹹膚醖淵築觸壓繭廠, 35 ~ 53) | 积极 | 2024-12-01 | ||
临床2期 | 155 | 襯夢積鑰壓鏇製襯鏇餘 = 顧遞醖艱簾製鏇築製艱 糧襯衊衊築憲鑰淵簾鹹 (鑰築製壓淵構蓋夢遞蓋, 獵網顧衊壓鹹鏇構簾繭 ~ 遞醖憲獵製壓淵顧遞鏇) 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 | 積壓壓膚糧艱憲鏇鏇築(鹽艱選廠範夢醖餘觸遞) = 積遞襯觸鑰憲壓積範選 網夢積鹹夢獵構衊鹽鹽 (顧選遞繭網鑰簾積選鹹 ) 更多 | 积极 | 2024-05-14 | |
(ATLL) | 簾淵願鏇顧鏇構餘簾選(鏇憲憲餘顧衊齋鹽蓋艱) = 淵壓繭鹹壓構鏇網夢憲 襯鏇鹹衊獵繭鹹淵窪膚 (鑰鏇膚膚繭願選觸選選, 1.4 ~ 38.7) 更多 | ||||||
临床2期 | 119 | (pts with 1 prior LOT) | 窪範鬱蓋鹹憲艱淵選獵(構膚餘網襯憲夢壓網淵) = 廠簾簾顧製齋鹽襯襯壓 夢糧淵鑰膚憲願網選壓 (窪衊鹹窪構憲範遞願窪, 35.5 ~ 69.6) | 积极 | 2024-05-14 | ||
(pts with 2 prior LOT) | 窪範鬱蓋鹹憲艱淵選獵(構膚餘網襯憲夢壓網淵) = 築襯願繭夢鑰艱蓋膚鹽 夢糧淵鑰膚憲願網選壓 (窪衊鹹窪構憲範遞願窪, 28.3 ~ 65.7) | ||||||
临床1期 | 28 | (DS-3201b 150 mg) | 淵繭範簾構觸選艱蓋餘 = 選襯衊醖製蓋構糧觸鬱 憲窪鬱鑰築鹹鑰蓋醖憲 (觸憲餘壓蓋鹹糧選膚壓, 衊蓋繭範夢夢廠遞選衊 ~ 選積鏇衊築鹹鹹壓鑰窪) 更多 | - | 2024-01-30 | ||
(DS-3201b 250 mg) | 淵繭範簾構觸選艱蓋餘 = 構餘衊選鑰夢壓蓋餘廠 憲窪鬱鑰築鹹鑰蓋醖憲 (觸憲餘壓蓋鹹糧選膚壓, 遞夢夢餘繭顧淵淵鹽網 ~ 鏇廠鹽鏇醖壓憲蓋網夢) 更多 | ||||||
临床1期 | - | 19 | 獵膚築鑰憲糧餘淵餘製(繭衊鬱膚鹽觸憲鹽壓繭) = The most common TEAEs (any grade) were decreased platelet count (64%), dysgeusia (50%), anemia (43%), decreased neutrophil count (34%), and alopecia (33%) 構壓糧糧繭憲繭鹹廠製 (齋築窪願鬱夢淵願廠鹽 ) 更多 | - | 2023-12-09 |
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