CEP-9722(CEP-9722) - 药物靶点：PARP1 x PARP2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PARP1 x PARP2

作用机制

PARP1抑制剂(聚腺苷二磷酸核糖聚合酶1抑制剂)、PARP2抑制剂(聚腺苷二磷酸核糖聚合酶2抑制剂)

治疗领域

肿瘤内分泌与代谢疾病呼吸系统疾病+ [3]

在研适应症-

非在研适应症

晚期恶性实体瘤套细胞淋巴瘤非小细胞肺癌+ [2]

原研机构

Teva Pharmaceutical Industries Ltd.

在研机构-

非在研机构

Cephalon, Inc.

Checkpoint Therapeutics, Inc.

Teva Pharmaceutical Industries Ltd.

最高研发阶段终止临床2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

分子式C24H26N4O3

InChIKeyCTLOSZHDGZLOQE-UHFFFAOYSA-N

CAS号916574-83-9

关联

3

项与 CEP-9722 相关的临床试验

NCT01311713 / Terminated临床1/2期

An Open-Label Study to Determine the Maximum Tolerated Dose of the PARP Inhibitor CEP-9722 When Administered as a Single Agent in Patients With Advanced or Metastatic Solid Tumors

CEP-9722 is an inhibitor of poly-adenosine diphosphate (ADP) ribose polymerase -1 and -2 (PARP). The primary purpose of this study is to (Part 1) determine the maximum tolerated dose (MTD) of CEP-9722 administered daily to participants with advanced or metastatic solid tumors, (Part 2) to evaluate the safety and tolerability of that dose, and to investigate whether CEP-9722 has antitumor activity as a single agent.

开始日期2011-05-02

申办/合作机构

Teva Branded Pharmaceutical Products R&D, Inc.

NCT01345357 / Completed临床1期

A Dose-Escalation Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP 1 and PARP 2 Inhibitor) in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma

The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors or mantle cell lymphoma.

开始日期2011-05-01

申办/合作机构

Cephalon, Inc.

NCT00920595 / Completed临床1期

An Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP-1 and PARP-2 Inhibitor) as Single-Agent Therapy and as Combination Therapy With Temozolomide in Patients With Advanced Solid Tumors

An open-label study to evaluate the safety, pharmacokinetics, and pharmacodynamics of CEP-9722 as single-agent therapy and as combination therapy with temozolomide in patients with advanced solid tumors.

开始日期2009-06-01

申办/合作机构

Cephalon, Inc.

100 项与 CEP-9722 相关的临床结果

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100 项与 CEP-9722 相关的转化医学

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100 项与 CEP-9722 相关的专利（医药）

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10

项与 CEP-9722 相关的文献（医药）

2023-05-11·BMC pulmonary medicine

The combination therapy of isomucronulatol 7-O-beta-glucoside (IMG) and CEP-9722 targeting ferroptosis-related biomarkers in non-small cell lung cancer (NSCLC)

Article

作者: Liu, Chao ; Cui, Xiaofei ; Bai, Yu ; Liu, Chang ; Dong, Penghua

BACKGROUNDNSCLC is a malignant tumor with a high incidence. Ferroptosis presents an essential function in regulating carcinogenesis and tumor progression. However, the ferroptosis-associated prognostic model based on single-cell sequencing of NSCLC remains unexplored. Our study aims to establish a potential predictive model for NSCLC patients and provide available targeted drugs for clinical treatment.METHODSThe data on NSCLC patients were collected from TCGA and GEO databases to analyze their gene expression profiles. ConsensusCluster was adopted to divide the patients into different groups based on ferroptosis-related genes. Then, the univariable Cox and LASSO analyses were applied to data analysis and model establishment. Single-cell analysis was used to explore the risk score genes in different cell populations and states. The protein levels of these genes were also investigated through the HPA database. Drug sensitivity was evaluated in CellMiner database. CCK8 and colony formation assays were performed to validate potential drugs' effects on lung cancer cell lines.RESULTSA ferroptosis-related prognostic model involving 14 genes in NSCLC patients was established. The risk score model was developed in training set GSE31210 and validated in the test set TCGA. The low-risk score group showed a better prognosis than the high-risk score group. The single-cell analysis revealed that the risk score genes were mainly derived from lung tumor cells. Most risk score genes were more highly expressed in tumor tissue than in normal tissue, according to the HPA database. Besides, these genes were associated with 106 drugs in CellMiner database. Finally, the drug effects on NSCLC cell growth were evaluated by cck8 and colony formation.CONCLUSIONSWe identified an effective ferroptosis-related prognostic model based on single-cell sequencing. The potential prediction model is devoted to exploring clinical therapeutic targets for NSCLC.

2018-12-01·Current Treatment Options in Oncology2区 · 医学

Using PARP Inhibitors in the Treatment of Patients With Ovarian Cancer

2区 · 医学

Review

作者: Kurnit, Katherine C ; Westin, Shannon N ; Coleman, Robert L

OPINION STATEMENTUse of poly(ADP-ribose) polymerase (PARP) inhibitors has greatly increased over the past 5 years. With several new Food and Drug Administration (FDA) approvals, three PARP inhibitors have entered into standard of care treatment for epithelial ovarian cancer (including ovarian, fallopian tube, and primary peritoneal cancer). Olaparib and rucaparib currently have indications for treatment of recurrent BRCA mutant ovarian cancer. Olaparib, rucaparib, and niraparib all have indications for maintenance therapy in recurrent platinum-sensitive ovarian cancer after response to platinum-based therapy. In our practice, we use both olaparib and rucaparib in the recurrent setting, and all three PARP inhibitors in the maintenance setting. Choice of which PARP inhibitor to use in either setting is largely based upon baseline laboratory values, number of prior therapies, and presence of a BRCA mutation and/or homologous recombination deficiency (HRD). As (HRD) and other biomarker assessments continue to improve, we anticipate being able to better identify which patients might most benefit from PARP inhibitor therapy in the future. The clinically available PARP inhibitors are currently undergoing extensive investigations in clinical trials. Other newer agents such as talazoparib, veliparib, 2X-121, and CEP-9722 are in earlier stages of development. As more FDA-approved indications for PARP inhibitor therapy in ovarian cancer become available, we anticipate the decision of which PARP inhibitor to use will become increasingly complex.

2016-04-01·Anti-Cancer Drugs4区 · 医学

An open-label, dose-escalation study to evaluate the safety and pharmacokinetics of CEP-9722 (a PARP-1 and PARP-2 inhibitor) in combination with gemcitabine and cisplatin in patients with advanced solid tumors

4区 · 医学

Article

作者: Gombos, Andrea ; Soria, Jean-Charles ; Campone, Mario ; Bahleda, Rastilav ; Frenel, Jean-Sebastien ; Bourbouloux, Emmanuelle ; Aftimos, Philippe ; Varga, Andrea ; Awada, Ahmad

Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors may potentiate chemotherapy by hindering DNA damage repair pathways. CEP-9722 is the prodrug of CEP-8983, a selective inhibitor of PARP-1 and PARP-2. Preclinical studies and a prior phase 1 study suggested that CEP-9722 may cause less myelosuppression than has been observed with other oral PARP inhibitors. The primary objective of this study was to determine the maximum-tolerated dose of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors. All patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 of a 21-day cycle. Patients who completed one cycle of chemotherapy alone continued chemotherapy in combination with CEP-9722 150, 200, 300, or 400 mg orally twice daily on days 2-7, with dose-limiting toxicity assessed in cycle 2. Patients experiencing clinical benefit could continue treatment until disease progression or unacceptable toxicity. Thirty-two patients enrolled; 18 patients completed cycle 1 and received chemotherapy plus CEP-9722. The median (range) treatment administration with CEP-9722 was five (1-12) cycles. No patient experienced dose-limiting toxicity with CEP-9722 treatment. Grade 3/4 hematologic adverse events included neutropenia (28%) and leukopenia (11%); adverse events led to discontinuation in 33% of patients. One patient achieved complete response, three had partial responses, and 11 had stable disease; however, the relative contribution of CEP-9722 and/or the chemotherapeutic agents cannot be determined from this single-arm design. This study was discontinued before determination of the maximum-tolerated dose because of highly variable CEP-8983 exposure in all cohorts and toxicity, particularly chemotherapy-induced myelosuppression.

100 项与 CEP-9722 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14882

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
实体瘤	临床2期	美国	Checkpoint Therapeutics, Inc.	2013-09-29
套细胞淋巴瘤	临床2期	比利时	Cephalon, Inc.	2011-05-01
套细胞淋巴瘤	临床2期	法国	Cephalon, Inc.	2011-05-01
晚期恶性实体瘤	临床2期	英国	Cephalon, Inc.	2009-06-01
晚期恶性实体瘤	临床2期	法国	Cephalon, Inc.	2009-06-01
非小细胞肺癌	临床2期	美国	Cephalon, Inc.	-
非小细胞肺癌	临床2期	美国	Cephalon, Inc.	-
非小细胞肺癌	临床2期	-	Teva Pharmaceutical Industries Ltd.	-
非小细胞肺癌	临床2期	-	Teva Pharmaceutical Industries Ltd.	-
卵巢癌	临床2期	-	Teva Pharmaceutical Industries Ltd.	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01311713 (CTgov)	临床1/2期	转移性实体瘤	45	CEP-9722 (CEP-9722 Dose 1 QD)	顧觸範鏇觸醖廠鹽憲獵(範餘襯鏇艱築襯鬱淵觸) = 淵鹹糧窪艱製夢構獵網積醖糧遞廠鑰廠艱繭廠 (簾鬱範構窪壓餘醖襯積, 糧顧獵觸衊糧選蓋鏇壓 ~ 遞築齋選網鹹蓋齋鑰憲) 更多	-	2024-01-30
				CEP-9722 (CEP-9722 Dose 1 BID)	顧觸範鏇觸醖廠鹽憲獵(範餘襯鏇艱築襯鬱淵觸) = 膚積窪製襯鏇膚選餘範積醖糧遞廠鑰廠艱繭廠 (簾鬱範構窪壓餘醖襯積, 艱膚憲廠觸築淵醖憲選 ~ 壓網齋餘蓋齋衊襯襯選) 更多