HDAC inhibitors(Histone deacetylase inhibitors), HDAC1 inhibitors(Histone deacetylase 1 inhibitors), HDAC2 inhibitors(Histone deacetylase 2 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Diffuse Large B-Cell LymphomaCutaneous T-Cell LymphomaPeripheral T-Cell Lymphoma+ [11]

Inactive Indication-

Originator Organization

Guizhou Bailing Group Pharmaceutical Co., Ltd.

Active Organization

Guizhou Bailing Group Pharmaceutical Co., Ltd.

West China HospitalChengdu Zenitar Biomedical Technology Co., Ltd

Inactive Organization-

License Organization

Guizhou Bailing Group Pharmaceutical Co., Ltd.

West China Hospital

Drug Highest PhasePhase 2/3

First Approval Date-

Regulation-

Clinical Trials associated with Purinostat Mesylate

CTR20241633

/ RecruitingPhase 1/2

注射用甲磺酸普依司他联合泊马度胺胶囊、低剂量地塞米松治疗复发或难治性多发性骨髓瘤患者的有效性和安全性的开放、平行对照、多中心Ib/IIa期临床研究

[Translation] An open, parallel-controlled, multicenter phase Ib/IIa clinical study on the efficacy and safety of prilocastat mesylate for injection combined with pomalidomide capsules and low-dose dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma

主要目的 Ib期确定注射用甲磺酸普依司他联合固定剂量泊马度胺胶囊、地塞米松在复发或难治性的多发性骨髓瘤（RRMM）患者中的最大耐受剂量（MTD），IIa期推荐剂量（RP2D）。 IIa期进一步评价RP2D剂量注射用甲磺酸普依司他联合固定剂量泊马度胺胶囊、地塞米松在复发或难治性多发性骨髓瘤（RRMM）患者中的初步有效性。次要目的 Ib期 1.评价注射用甲磺酸普依司他联合固定剂量泊马度胺胶囊、地塞米松在治疗复发或难治性多发性骨髓瘤（RRMM）患者中的安全性和耐受性； 2.评价注射用甲磺酸普依司他联合固定剂量泊马度胺胶囊、地塞米松后在复发或难治性多发性骨髓瘤（RRMM）患者中的药代动力学指标和药效学指标； 3.观察注射用甲磺酸普依司他联合固定剂量泊马度胺胶囊、地塞米松在复发或难治性多发性骨髓瘤（RRMM）患者中的疗效。 IIa期 1.评价注射用甲磺酸普依司他联合固定剂量泊马度胺胶囊、地塞米松在复发或难治性多发性骨髓瘤（RRMM）患者中的安全性和耐受性。 2.评估注射用甲磺酸普依司他联合固定剂量泊马度胺胶囊、地塞米松在复发或难治性多发性骨髓瘤（RRMM）患者中的群体药代动力学特征。

[Translation]

Main Objective Phase Ib To determine the maximum tolerated dose (MTD) and Phase IIa recommended dose (RP2D) of prilocastat mesylate for injection combined with fixed-dose pomalidomide capsules and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). Phase IIa To further evaluate the preliminary efficacy of RP2D dose of prilocastat mesylate for injection combined with fixed-dose pomalidomide capsules and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). Secondary objectives Phase Ib 1. To evaluate the safety and tolerability of prilocastat mesylate for injection combined with fixed-dose pomalidomide capsules and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (RRMM); 2. To evaluate the pharmacokinetic and pharmacodynamic indicators of prilocastat mesylate for injection combined with fixed-dose pomalidomide capsules and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM); 3. To observe the efficacy of prilocastat mesylate for injection combined with fixed-dose pomalidomide capsules and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). Phase IIa 1. To evaluate the safety and tolerability of prilocastat mesylate for injection combined with fixed-dose pomalidomide capsules and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). 2. To evaluate the population pharmacokinetic characteristics of prilocastat mesylate for injection combined with fixed-dose pomalidomide capsules and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM).

Start Date05 Jun 2024

Sponsor / Collaborator

Chengdu Zenitar Biomedical Technology Co., Ltd

CTR20241672

/ RecruitingPhase 1/2

一项评价注射用甲磺酸普依司他联合用药治疗晚期实体瘤的安全性、耐受性、药代动力学和初步疗效的开放性、多中心Ⅰb/IIa 期临床研究

[Translation] An open-label, multicenter Phase Ib/IIa clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of prilocastat mesylate for injection combined with other drugs in the treatment of advanced solid tumors

主要目的 Ib 期评价甲磺酸普依司他联合用药治疗晚期实体瘤的安全性、耐受性；并探索甲磺酸普依司他联合用药在晚期实体瘤患者中的剂量限制性毒性（DLT）、最大耐受剂量（MTD）；确定甲磺酸普依司他联合用药治疗晚期实体瘤的II 期推荐剂量（RP2D）。 IIa 期进一步评价甲磺酸普依司他联合用药在晚期实体瘤患者中的初步疗效。次要目的 Ib 期评价甲磺酸普依司他单药治疗晚期实体瘤的安全性、耐受性；？评价甲磺酸普依司他联合用药在晚期实体瘤患者中的初步疗效；？评价甲磺酸普依司他联合用药治疗晚期实体瘤的药代动力学特征。 IIa 期进一步评价甲磺酸普依司他联合用药治疗晚期实体瘤的安全性、耐受性；评价甲磺酸普依司他联合用药治疗晚期实体瘤的药代动力学特征。探索性目的评估甲磺酸普依司他联合用药治疗晚期实体瘤生物标志物药效学意义

[Translation]

Primary Objective Phase Ib To evaluate the safety and tolerability of prilocastat mesylate combined with other drugs in the treatment of advanced solid tumors; and to explore the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of prilocastat mesylate combined with other drugs in patients with advanced solid tumors; to determine the Phase II recommended dose (RP2D) of prilocastat mesylate combined with other drugs in the treatment of advanced solid tumors. Phase IIa To further evaluate the preliminary efficacy of prilocastat mesylate combined with other drugs in patients with advanced solid tumors. Secondary Objective Phase Ib To evaluate the safety and tolerability of prilocastat mesylate monotherapy in the treatment of advanced solid tumors;? To evaluate the preliminary efficacy of prilocastat mesylate combined with other drugs in patients with advanced solid tumors;? To evaluate the pharmacokinetic characteristics of prilocastat mesylate combined with other drugs in the treatment of advanced solid tumors. Phase IIa To further evaluate the safety and tolerability of prilocastat mesylate combined with other drugs in the treatment of advanced solid tumors; and to evaluate the pharmacokinetic characteristics of prilocastat mesylate combined with other drugs in the treatment of advanced solid tumors. Exploratory objective To evaluate the pharmacodynamic significance of biomarkers in combination therapy with prilocastat mesylate in the treatment of advanced solid tumors

Start Date23 May 2024

Sponsor / Collaborator

Chengdu Zenitar Biomedical Technology Co., Ltd

NCT06431243

/ RecruitingPhase 1/2

An Open, Multicenter Phase Ib/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the Purinostat Mesylate for Injection in Combination Therapy for Advanced Solid Tumors

Primary Objectives Phase Ib To evaluate the safety and tolerability of Purinostat Mesylate in combination therapy for advanced solid tumors; and to explore the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of Purinostat Mesylate in combination therapy in patients with advanced solid tumors.
To determine the recommended Phase II dose (RP2D) of Purinostat Mesylate in combination therapy for advanced solid tumors.
Phase IIa To further evaluate the preliminary efficacy of Purinostat Mesylate in combination therapy in patients with advanced solid tumors.
Secondary Objectives Phase Ib To evaluate the safety and tolerability of Purinostat Mesylate Monotherapy for the treatment of advanced solid tumors; To evaluate the preliminary efficacy of Purinostat Mesylate in combination therapy in patients with advanced solid tumors; To evaluate the pharmacokinetic characteristics of Purinostat Mesylate in combination therapy for the treatment of advanced solid tumors.
Phase IIa To further evaluate the safety and tolerability of Purinostat Mesylate in combination therapy for advanced solid tumors.
To evaluate the pharmacokinetic characteristics of Purinostat Mesylate in combination therapy for advanced solid tumors.
Exploratory Objectives To assess the pharmacodynamic characteristics in Purinostat Mesylate combination therapy for advanced solid tumors.

Start Date08 May 2024

Sponsor / Collaborator

Chengdu Zenitar Biomedical Technology Co., Ltd

100 Clinical Results associated with Purinostat Mesylate

100 Translational Medicine associated with Purinostat Mesylate

100 Patents (Medical) associated with Purinostat Mesylate

Literatures (Medical) associated with Purinostat Mesylate

01 Mar 2023·Bioactive Materials

HDAC I/IIb selective inhibitor Purinostat Mesylate combined with GLS1 inhibition effectively eliminates CML stem cells

Article

Author: Qiu, Qiang ; Zheng, Li ; Li, Ning ; Qiu, Huandi ; Feng, Yunyu ; Wang, Fang ; Yang, Zhuang ; Li, Zhihui ; Zhu, Zejiang ; Yang, Yunfan ; Yang, Linyu ; Sun, Yuanyuan ; Pan, Cong ; He, Wei ; Yi, Yuyao ; Hu, Yiguo ; Cui, Xue ; Tang, Minghai ; Chen, Lijuan

Purinostat Mesylate (PM) is a novel highly selective and active HDAC I/IIb inhibitor, and the injectable formulation of PM (PMF) based on the compound prescription containing cyclodextrin completely can overcome PM's poor solubility and improves its stability and pharmacokinetic properties. Here, we showed that PM effectively repressed the survival of Ph⁺ leukemia cells and CD34⁺ leukemia cells from CML patients in vitro. In vivo studies demonstrated that PMF significantly prevented BCR-ABL(T315I) induced CML progression by restraining leukemia stem cells (LSCs), which are insensitive to chemotherapy and responsible for CML relapse. Mechanism studies revealed that targeting HDAC I/IIb repressed several important factors for LSCs survival including c-Myc, β-Catenin, E2f, Ezh2, Alox5, and mTOR, as well as interrupted some critical biologic processes. Additionally, PMF increased glutamate metabolism in LSCs by increasing GLS1. The combination of PMF and glutaminase inhibitor BPTES synergistically eradicated LSCs by altering multiple key proteins and signaling pathways which are critical for LSC survival and self-renewal. Overall, our findings represent a new therapeutic strategy for eliminating LSCs by targeting HDAC I/IIb and glutaminolysis, which potentially provides a guidance for PMF clinical trials in the future for TKI resistance CML patients.

31 Dec 2022·Annals of MedicineQ3 · MEDICINE

Therapeutic efficacy of an injectable formulation of purinostat mesylate in SU-DHL-6 tumour model

Q3 · MEDICINE

Article

Author: Bai, Peng ; Chen, Lijuan ; Yang, Zhuang ; Pei, Heying ; Tang, Minghai ; Xu, Yaohui ; Zhu, Zejiang ; He, Jun ; Wen, Jiaolin ; Li, Dan

Background: Previous studies have proven that Purinostat Mesylate (PM) is a new HDAC inhibitor and exhibits significant antitumor efficacy. However, the clinical application of PM was greatly limited by its poor solubility in water and low bioavailability.Objective:To increase the solubility of PM through pharmaceutical research, and prepare it into an injection that meets the needs of intravenous use to promote its clinical application.MethodsThe prepared PM/HP-β-CD inclusion complex was studied by computer simulation, fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (1H-NMR spectroscopy), and scanning electron microscopy (SEM). Then, the antitumor effects of PM/HP-β-CD inclusion complex were studied by in vitro cytotoxicity assay, apoptosis assay, pharmacokinetic study and in vivo antitumor assay.Results:Phase Solubility Analysis revealed that PM and HP-β-CD were compatible and the solubility of PM increased almost 220 times, to 2.02 mg/mL. The interaction mechanism studies revealed that PM could be embedded into the cavity of HP-β-CD through the side of the aminobenzene ring. Cell viability and apoptosis assays showed that PM/HP-β-CD complex maintained the good anti-cancer activity of PM, and PM/HP-β-CD complex has a better anti-tumor effect and lower toxicity than LBH589 and Hyper-CVAD/RTX in vivo. All the results suggest that HP-β-CD can solve the problem of PM administration and provide a way for clinical application of PM.Conclusions: In this study, an injectable formulation of PM in HP-β-CD (10% w/v) was prepared to improve its water solubility. Our research provides a way for clinical administration of PM, which has been under phase I clinical trial for the treatment of relapsed or refractory B-cell-related hematologic malignancies in China and the USA.KEY MESSAGESWe developed a preparation of Purinostat Mesylate that can be administered intravenously, reducing the toxicity associated with oral administration.This preparation has an outstanding therapeutic effect on SU-DHL-6 xenograft tumour, indicating its clinical value, which has been under phase I clinical trial for the treatment of relapsed or refractory B-cell-related haematologic malignancies in China and the USA.

14 Sep 2022·Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

[In vitro pharmacodynamic studies of novel class Ⅰ and Ⅱb selective histone deacetylase inhibitor purinostat mesylate in the treatment of diffuse large B-cell lymphoma and its mechanism].

Article

Author: Chen, L J ; Niu, T ; Zhao, A L ; Wang, J ; Yang, L Y ; Li, H

Objective: To investigate the in vitro inhibitory activity of a novel class Ⅰ and Ⅱb selective histone deacetylase (HDAC) inhibitor, purinostat mesylate (PM) , in diffuse large B-cell lymphoma and its mechanism. Methods: The 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide method was used to detect the effect of PM on cell proliferation. The effects of PM on cell cycle and apoptosis were detected by flow cytometry. The acetylation levels of HDAC substrate, cell cycle protein, apoptosis-related protein, and oncogene protein expression were detected by Western blot. Results: PM significantly inhibited the proliferation of lymphoma SUDHL-4 and SUDHL-6 cells and increased the acetylation levels of HDAC substrates H3, H4, and α-tubulin. In cell cycle experiments, PM induced G(0)/G(1) phase arrest in SUDHL-4 and SUDHL-6 cells. Western blot experiment showed that PM could significantly downregulate the expression of cyclin-dependent kinases Cdk2, Cdk4, Cdk6, cyclin D1, and cyclin E and upregulate the expression of CDK inhibitor protein p21. In the apoptosis experiment, PM could induce the apoptosis of SUDHL-4 and SUDHL-6 cells. Western blot experiment demonstrated that PM promoted endogenous apoptosis by activating caspase-3 kinase and affecting antiapoptotic protein Bcl-2. In addition, PM could downregulate the expression of oncogene marker proteins MYC, IKZF1, and IKZF3. Conclusion: PM has an efficient biological activity in vitro for diffuse large B-cell lymphoma, including double-hit lymphoma, and provides valuable experimental evidence for PM in clinical treatment.

100 Deals associated with Purinostat Mesylate

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diffuse Large B-Cell Lymphoma	Phase 3	China	Chengdu Zenitar Biomedical Technology Co., Ltd	22 Mar 2024
Cutaneous T-Cell Lymphoma	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	14 Apr 2024
Peripheral T-Cell Lymphoma	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	14 Apr 2024
Refractory Multiple Myeloma	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	25 Mar 2024
Relapse multiple myeloma	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	25 Mar 2024
Diffuse large B-cell lymphoma recurrent	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	08 Nov 2022
Diffuse large B-cell lymphoma refractory	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	08 Nov 2022
Acute Lymphoblastic Leukemia	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	30 Jan 2022
Multiple Myeloma	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	30 Jan 2022
T-Cell Leukemia	Phase 2	China	Chengdu Zenitar Biomedical Technology Co., Ltd	30 Jan 2022

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05563844 (ASCO2024) Manual	Phase 2	Diffuse Large B-Cell Lymphoma double-expressor (DEL) \| TP53 abnormal	28	Purinostat Mesylate 8.4 mg/m2	(mjahtifyxl) = jjknecjach wznfawomlz (wzviogkuzj, 38.4 - 88.2) View more	Positive	02 Jun 2024
NCT05563844 (ASCO2024) Manual	Phase 2		28	Purinostat Mesylate 11.2 mg/m2	(mjahtifyxl) = kohdrnxbzq wznfawomlz (wzviogkuzj, 46.2 - 95.0)	Positive	02 Jun 2024
ICML2023	Phase 1	Recurrent Lymphoma \| Refractory Lymphoma	18	Purinostat Mesylate	(nekvlxhkbs) = tumxhmntzg cjilwfsaja (xeknvwbmdk ) View more	Positive	09 Jun 2023

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