TBR-065(TBR-065) - 药物靶点：D2 receptor x SSTR2_在研适应症：肢端肥大症_专利_临床

概要

基本信息

药物类型

融合蛋白

别名

+ [1]

靶点

D2 receptor x SSTR2

作用机制

D2 receptor激动剂(多巴胺D2受体激动剂)、SSTR2激动剂(生长抑素受体2激动剂)

治疗领域

神经系统疾病内分泌与代谢疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

肢端肥大症

非在研适应症

垂体ACTH分泌过多

原研机构

Ipsen SA

在研机构

Tiburio Therapeutics, Inc.初创企业

非在研机构

Ipsen SA

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

3

项与 TBR-065 相关的临床试验

NCT03045302 / Terminated临床2期

A Phase IIa, Open-label, Single-arm, Two Stage, Multi-centre Study to Investigate the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Repeated Subcutaneous Administration of BIM23B065 in Subjects With Acromegaly

The purpose of the protocol is evaluate the safety, the pharmacodynamics and the pharmacokinetic of repeated administration of BIM23B065 in subjects with acromegaly.

开始日期2017-01-26

申办/合作机构

Ipsen SA

EUCTR2015-003868-37-BE / Not yet recruiting临床2期

A phase IIa, open-label, single-arm, two stage, multi-centre study to investigate the pharmacodynamics, pharmacokinetics, safety and tolerability of repeated subcutaneous administration of BIM23B065 in subjects with acromegaly

开始日期2016-09-29

申办/合作机构

Ipsen Pharma SAS

NL-OMON41949 / CompletedN/AIIT

A phase I, double-blind, randomised, placebo-controlled study, in three parts (parts A, B and C) to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of BIM23B065 administered subcutaneously as single and multiple ascending doses to young healthy male subjects - BIM23B065 in healthy volunteers

开始日期2015-03-25

申办/合作机构

Centre for Human Drug Research

100 项与 TBR-065 相关的临床结果

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100 项与 TBR-065 相关的转化医学

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100 项与 TBR-065 相关的专利（医药）

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6

项与 TBR-065 相关的文献（医药）

2021-06-01·Pituitary2区 · 医学

Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells

2区 · 医学

Article

作者: Cuny, Thomas ; Mougel, Grégory ; Graillon, Thomas ; Barlier, Anne ; Brue, Thierry ; Landsman, Tanya ; Halem, Heather A ; Zhang, Shengwen ; Defilles, Célines ; Culler, Michael D ; Datta, Rakesh ; Dufour, Henry ; Figarella-Branger, Dominique ; Saveanu, Alexandru

CONTEXTSomatostatin (SST) and dopamine (DA) inhibit growth hormone (GH) secretion and proliferation of GH-secreting pituitary adenomas (GHomas) through binding to SSTR2 and D2R receptors. Chimeric SST-DA compounds (Dopastatins) display increased potency in inhibiting GH secretion, as compared with individual SST or DA analogs (alone or combined).OBJECTIVETo assess the efficacy of a second-generation dopastatin, TBR-065, in suppressing GH secretion from human GH- and GH/prolactin(PRL)-omas.DESIGNWe compared the ability of TBR-065 to inhibit GH secretion from primary cultures of human GH- or GH/PRLoma cells to that of the first generation dopastatin, TBR-760 (formerly BIM-23A760), octreotide (OCT) and cabergoline (CAB), the later either alone or combined. We investigated whether there was any impact of BIM-133, the metabolite of TBR-065, on the ability of TBR-065 to inhibit GH in these cultures.METHODS17 GH- and GH/PRLomas were included in this study. Inhibition of GH secretion by TBR-065, TBR-760, OCT and CAB (0.1 pM to 0.1 µM) was assessed over a period of 8 h.RESULTSAll tumors expressed SSTR2 and D2R mRNAs. GH suppression was higher with TBR-065 as compared with TBR-760 (E_max = 57 ± 5.6% vs. 41.1 ± 12.5%, respectively, p < 0.001) or with OCT + CAB (E_max = 56.8 ± 7.2% vs. 44.4 ± 9.4%, p < 0.001). BIM-133 did not have any impact on the activity of TBR-065.CONCLUSIONTBR-065 has significantly improved efficacy in suppressing GH secretion as compared to current available therapies and may represent a new promising option for the treatment of acromegaly.

2021-01-01·Neuroendocrinology2区 · 医学

Efficacy of a Novel Second-Generation Somatostatin-Dopamine Chimera (TBR-065) in Human Medullary Thyroid Cancer: A Preclinical Study

2区 · 医学

Article

作者: Saronni, Davide ; Vitale, Giovanni ; Borghi, Maria Orietta ; Albertelli, Manuela ; Ferone, Diego ; Persani, Luca ; Dicitore, Alessandra ; Carra, Silvia ; Gaudenzi, Germano ; Hofland, Leo J ; Cantone, Maria Celeste

Introduction: Somatostatin and dopamine (DA) receptors have a pivotal role in controlling hormone secretion and cell proliferation in different neuroendocrine neoplasms, including medullary thyroid cancer (MTC). In the present preclinical study, we evaluated the anti-tumor activity of TBR-065 (formerly BIM-23B065), a second-generation somatostatin-DA chimera, in 2 human MTC cell lines. Methods: The effects of lanreotide (LAN) and TBR-065 on cell growth and proliferation, calcitonin (CT) secretion, cell cycle, apoptosis, cell migration, and tumor-induced angiogenesis have been evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DNA flow cytometry with propidium iodide (PI), Annexin V-FITC/PI staining, electrochemiluminescence immuno assay, wound-healing assay, and zebrafish platform, respectively. Results: TBR-065 exerted a more prominent anti-tumor activity than LAN in both MTC cell lines, as shown by inhibition of cell proliferation (maximal inhibition in TT: −50.3 and −37.6%, respectively; in MZ-CRC-1: −58.8 and −27%, respectively) and migration (in TT: −42.7 and −22.9%, respectively; in MZ-CRC-1: −75.5 and −58.2%, respectively). Only the new chimera decreased significantly the fraction of cells in S phase (TT: −33.8%; MZ-CRC-1: −18.8%) and increased cells in G2/M phase (TT: +13%; MZ-CRC-1: +30.5%). In addition, TBR-065 exerted a more prominent pro-apoptotic effect than LAN in TT cells. A concomitant decrease in CT secretion was observed after 2 days of incubation with both drugs, with a more relevant effect of TBR-065. However, neither LAN nor TBR-065 showed any effect on tumor-induced angiogenesis, as evaluated using a zebrafish/tumor xenograft model. Discussion/Conclusion: In MTC cell lines, a second-generation somatostatin-DA analog, TBR-065, exerts a more relevant anti-tumor activity than LAN, through modulation of cell cycle, induction of apoptosis, and reduction in migration. Further studies are required to establish whether TBR-065 has comparable potent inhibitory effects on tumor growth in vivo.

2020-06-01·Journal of Pharmacokinetics and Pharmacodynamics3区 · 医学

Quantification of the endogenous growth hormone and prolactin lowering effects of a somatostatin-dopamine chimera using population PK/PD modeling

3区 · 医学

Article

作者: van der Graaf, Piet H ; Burggraaf, Jacobus ; Stevens, Jasper ; Dehez, Marion ; van Esdonk, Michiel J

AbstractA phase 1 clinical trial in healthy male volunteers was conducted with a somatostatin-dopamine chimera (BIM23B065), from which information could be obtained on the concentration-effect relationship of the inhibition of pulsatile endogenous growth hormone and prolactin secretion. Endogenous growth hormone profiles were analyzed using a two-step deconvolution-analysis-informed population pharmacodynamic modeling approach, which was developed for the analyses of pulsatile profiles. Prolactin concentrations were modelled using a population pool model with a circadian component on the prolactin release. During treatment with BIM23B065, growth hormone secretion was significantly reduced (maximal effect [EMAX] = − 64.8%) with significant reductions in the pulse frequency in two out of three multiple ascending dose cohorts. A circadian component in prolactin secretion was identified, modelled using a combination of two cosine functions with 24 h and 12 h periods. Dosing of BIM23B065 strongly inhibited (EMAX = − 91%) the prolactin release and demonstrated further reduction of prolactin secretion after multiple days of dosing. This study quantified the concentration-effect relationship of BIM23B065 on the release of two pituitary hormones, providing proof of pharmacology of the chimeric actions of BIM23B065.

100 项与 TBR-065 相关的药物交易

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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
肢端肥大症	临床2期	-	Tiburio Therapeutics, Inc.初创企业	-
垂体ACTH分泌过多	临床1期	美国	Ipsen SA	-

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临床结果

适应症

分期

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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


NCT03045302 (DOPAACRO 002, CTgov)	临床2期	肢端肥大症	4	BIM23B065	範願顧鬱齋獵簾繭構淵(夢獵顧壓鏇鏇製範糧獵) = 獵鹹齋鹹壓齋壓醖構衊獵憲簾選衊艱蓋鬱窪構 (築夢範製淵憲淵廠鑰廠, 醖艱糧構繭觸鏇壓網築 ~ 襯蓋築選鹽鏇製淵壓襯) 更多	-	2019-03-08