CUDC-101(CUDC-101) - 药物靶点：EGFR x HDACs x HER2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

CUDC 101

靶点

EGFR x HDACs x HER2

作用方式

拮抗剂、抑制剂

作用机制

EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、HDAC抑制剂(组蛋白去乙酰化酶家族抑制剂)、HER2拮抗剂(受体蛋白酪氨酸激酶 erbB-2拮抗剂)

治疗领域

肿瘤神经系统疾病消化系统疾病+ [2]

在研适应症-

非在研适应症

晚期非小细胞肺癌晚期恶性实体瘤脑转移瘤+ [4]

原研机构

Curis, Inc.

在研机构-

非在研机构

Curis, Inc.

权益机构-

最高研发阶段终止临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C24H26N4O4

InChIKeyPLIVFNIUGLLCEK-UHFFFAOYSA-N

CAS号1012054-59-9

关联

5

项与 CUDC-101 相关的临床试验

EUCTR2012-003064-47-GB

/ Not yet recruitingN/A

A Phase 1 open-label study to investigate the pharmacodynamics, metabolomics and pharmacokinetics of CUDC-101 in subjects with HER2 positive invasive breast cancer.

开始日期2012-12-11

申办/合作机构

Curis, Inc.

NCT01702285

/ Terminated临床1期

A Phase I Open Label, Multicenter, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Orally Administered CUDC-101 in Subjects With Advanced and Refractory Solid Tumors

The main purpose of this study is to determine the safety and tolerability of orally administered CUDC-101 in cancer patients, and to determine a dose for further testing. This study will also determine how well CUDC-101 is absorbed into the blood after being given orally, assess CUDC-101 blood levels and what happens to the study drug in the body, and study how the body reacts to the study drug and what effects it has on tumors. CUDC-101 has been administered to cancer patients as an intravenous (IV) infusion in other research studies, but has not been studied when given orally.

开始日期2012-09-01

申办/合作机构

Curis, Inc.

NCT01384799

/ Completed临床1期

A Phase I Dose Escalation Study to Investigate the Safety and Pharmacokinetics of Intravenous CUDC-101 With Concurrent Cisplatin and Radiation Therapy in Subjects With Locally Advanced Head and Neck Cancer

This is a phase I dose escalation study of CUDC-101 in combination with concurrent cisplatin and radiation therapy in patients with locally advanced head and neck cancer. CUDC-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor Type 2 (Her2) and histone deacetylase (HDAC). The study is designed to establish the safety, tolerability and maximum tolerated dose (MTD) of CUDC-101 when administered in combination with concurrent cisplatin and radiation over an 8-week treatment course, consisting of a one week run-in period of CUDC-101 administered alone, followed by seven weeks of combination treatment with CUDC-101, cisplatin and radiation therapy.

开始日期2011-11-01

申办/合作机构

Curis, Inc.

100 项与 CUDC-101 相关的临床结果

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100 项与 CUDC-101 相关的转化医学

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100 项与 CUDC-101 相关的专利（医药）

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131

项与 CUDC-101 相关的文献（医药）

2025-06-01·Advanced Science

IR783‐Stabilized Nanodrugs Enhance Anticancer Immune Response by Synergizing Oxidation Therapy and Epigenetic Modulation

Article

作者: Wu, Meicen ; Lyu, Qingyang ; Chen, Kang ; Liu, Jinzhao ; Fan, Ni ; Yang, Chang ; Wang, Weiping

Abstract:

Immune evasion and metastasis are the leading causes of poor prognosis in triple‐negative breast cancer treatment. Since current standard immunotherapies have limited efficacy due to immunologically cold microenvironment, it is crucial to explore new strategies to sensitize anticancer immune response. In this study, it is found that incorporating β‐lapachone‐based oxidation therapy with CUDC101‐initiated epigenetic regulation results in synergistic antitumor effects and potent immune activation. To co‐deliver these two hydrophobic drugs, IR783 with cyanine structure serves as the stabilizer to form a nanoformulation based on small molecule self‐assembly. Such IR783‐stabilized nanodrugs can not only lead to cancer cell apoptosis through HDAC inhibition‐enhanced oxidation therapy but also cooperatively induce immunogenic cell death and promote pro‐inflammatory cytokine gene expression to reshape immunosuppressive microenvironment. Besides, nanodrugs can inhibit both primary and distant tumor growth effectively by elevating systemic anticancer immunity. This study provides a promising approach to synergize oxidation therapy with epigenetic modulation for safe and efficient breast cancer immunotherapy.

2025-06-01·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

NAT2 activity increases cytotoxicity of anthracycline antibiotics and HDAC inhibitors

Article

作者: Haberek, Wawrzyniec ; Kundu, Snehangshu ; Zhang, Xiaonan ; Globisch, Daniel ; Sjöblom, Tobias ; Rameika, Natallia ; Stoimenov, Ivaylo ; Rendo, Verónica ; Correia, Mario S P ; Tsiara, Ioanna

The Arylamine-N-acetyltransferase-2 (NAT2) enzyme is involved in metabolism of commonly used drugs driving differences in efficacy and tolerability of treatments. To bridge the current knowledge gap on metabolism of cytotoxic drugs by NAT2, and identify anticancer agents whose effects depend on NAT2 activity, we assessed 147 clinically used drugs. Hit compounds were evaluated for metabolic conversion by acetylation in presence of recombinant NAT2. Among those 147 drugs we found doxorubicin, daunorubicin, epirubicin, valrubicin, teniposide, afatinib, carmustine, vincristine, panobinostat, and vorinostat to have increased toxicity to cancer cells expressing the rapid NAT2 allele. Additionally, we report NAT2-mediated acetylation of idarubicin, daunorubicin, doxorubicin, vorinostat, and CUDC-101. These findings have implications for pharmacogenomics and cancer precision medicine using conventional chemotherapeutic drugs, as improving their efficacy and safety may affect >4 million cancer patients worldwide that receive these drugs as standard of care.

2025-04-20·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[A pan-cancer analysis of PYCR1 and its predictive value for chemotherapy and immunotherapy responses in bladder cancer].

Article

作者: Liu, Hongwei ; Li, Yutong ; Dong, Xuan ; Song, Xingyu ; Sun, Ruixu

OBJECTIVES:

To explore the potential of pyrroline-5-carboxylate reductase 1 (PYCR1) as a pan-cancer biomarker and investigate its expression, function, and clinical significance in bladder cancer (BLCA).

METHODS:

Bioinformatics analysis was conducted to evaluate the associations of PYCR1 with prognosis, immune microenvironment remodeling, tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer patients. Using the TCGA-BLCA dataset, univariate and multivariate regression analyses were performed to assess the potential of PYCR1 as an independent prognostic risk factor for BLCA, and a clinical decision model was constructed. The IMvigor210 cohort was utilized to evaluate the potential of PYCR1 for independently predicting the efficacy of immunotherapy. The pRRophetic was employed to screen candidate chemotherapeutic agents for treating BLCA with high PYCR1 expression. The CMap-XSum algorithm and molecular docking techniques were used to explore and validate small molecule inhibitors of PYCR1.

RESULTS:

A high expression of PYCR1 was significantly associated with poor prognosis, immune cell infiltration, TMB and MSI in various tumors (r>0.3). PYCR1 was overexpressed in BLCA, and high PYCR1 expression was closely related to poor prognosis in BLCA patients (HR: 1.14, 95% CI: 1.02-1.68, P=0.006). The IC₅₀ of the anti-cancer drugs cetuximab, 5-fluorouracil, and doxorubicin increased significantly in BLCA cell lines with high PYCR1 expressions (P<0.0001).

CONCLUSIONS:

High PYCR1 expression is an independent risk factor for poor prognosis in BLCA patients and can serve as a significant indicator for clinical decision-making as well as a marker for predicting sensitivity to chemotherapeutic agents and the efficacy of immunotherapy.

100 项与 CUDC-101 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12174

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
脑转移瘤	临床1期	美国	Curis, Inc.	2012-09-01
头颈部鳞状细胞癌	临床1期	美国	Curis, Inc.	2011-11-01
晚期非小细胞肺癌	临床1期	美国	Curis, Inc.	2010-07-01
乳腺癌	临床1期	美国	Curis, Inc.	2010-07-01
肝癌	临床1期	美国	Curis, Inc.	2010-07-01
胃癌	临床1期	美国	Curis, Inc.	2010-07-01
晚期恶性实体瘤	临床1期	美国	Curis, Inc.	2008-08-01