Pegylated thrombopoietin mimetic peptide(Pegylated thrombopoietin mimetic peptide) - 药物靶点：TPO receptor_在研适应症：贫血，血小板减少症，急性髓性白血病_专利_临床

概要

基本信息

药物类型

合成多肽

别名

PEG-TPOM

+ [1]

靶点

TPO receptor

作用机制

TPO receptor激动剂(血小板生成素受体激动剂)

治疗领域

血液及淋巴系统疾病肿瘤

在研适应症

贫血血小板减少症急性髓性白血病+ [1]

非在研适应症-

原研机构-

在研机构

Johnson & Johnson

Montefiore Medical Center

Janssen Pharmaceuticals, Inc.

非在研机构

Janssen Research & Development LLC

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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序列信息

Sequence Code 1277664501

来源: *****

关联

2

项与 Pegylated thrombopoietin mimetic peptide 相关的临床试验

NCT03990519 / Completed临床1期

A Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of a Single Subcutaneous Dose of JNJ-26366821 in Healthy Volunteers

The purpose of this study is to evaluate the safety and tolerability of a single subcutaneous (SC) dose of JNJ-26366821.

开始日期2019-06-24

申办/合作机构

Janssen Research & Development LLC

EUCTR2007-007520-17-BE / Unknown statusN/A

A Multicenter, Randomized, Double-Blind, Parallel Group Study to Evaluate the Effect of RWJ-800088 on The Prevention of Chemotherapy-Induced Anemia and The Prevention of Chemotherapy-Induced Thrombocytopenia in Subjects with Non-Small Cell Lung Cancer Receiving Gemcitabine and Either Carboplatin or Cisplatin - n/a

开始日期2008-07-25

申办/合作机构-

100 项与 Pegylated thrombopoietin mimetic peptide 相关的临床结果

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100 项与 Pegylated thrombopoietin mimetic peptide 相关的转化医学

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100 项与 Pegylated thrombopoietin mimetic peptide 相关的专利（医药）

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82

项与 Pegylated thrombopoietin mimetic peptide 相关的文献（医药）

2024-12-31·Platelets

Role of platelet count in a murine stasis model of deep vein thrombosis

Article

作者: Nguyen, Khanh P ; Le-Cook, Anh ; Lorentz, Christina U ; Mathews, Rick ; Hinds, Monica T ; Revenko, Alexey ; Setthavongsack, Naly ; Woltjer, Randall L ; Kaempf, Andy ; Loftis, Jennifer M

Platelets are core components of thrombi but their effect on thrombus burden during deep vein thrombosis (DVT) has not been fully characterized. We examined the role of thrombopoietin-altered platelet count on thrombus burden in a murine stasis model of DVT. To modulate platelet count compared to baseline, CD1 mice were pretreated with thrombopoietin antisense oligonucleotide (THPO-ASO, 56% decrease), thrombopoietin mimetic (TPO-mimetic, 36% increase), or saline (within 1%). Thrombi and vein walls were examined on postoperative days (POD) 3 and 7. Thrombus weights on POD 3 were not different between treatment groups (p = .84). The mean thrombus weights on POD 7 were significantly increased in the TPO-mimetic cohort compared to the THPO-ASO (p = .005) and the saline (p = .012) cohorts. Histological grading at POD 3 revealed a significantly increased smooth muscle cell presence in the thrombi and CD31 positive channeling in the vein wall of the TPO-mimetic cohort compared to the saline and THPO-ASO cohorts (p < .05). No differences were observed in histology on POD 7. Thrombopoietin-induced increased platelet count increased thrombus weight on POD 7 indicating platelet count may regulate thrombus burden during early resolution of venous thrombi in this murine stasis model of DVT.

2024-10-01·International Journal of Pharmaceutics

Engineered polymeric excipients for enhancing the stability of protein biologics: Poly(N-isopropylacrylamide)-poly(ethylene glycol) (PNIPAM-PEG) block copolymers

Article

作者: Won, You-Yeon ; Shin, Sung-Ho ; Jun, Taesuk

Protein therapeutics, particularly antibodies, depend on maintaining their native structures for optimal function. Hydrophobic interfaces, such as the air-water interface, can trigger protein aggregation and denaturation. While completely avoiding such interfacial exposures during manufacturing and storage is impractical, minimizing them is crucial for enhancing protein drug stability and extending shelf life. In the biologics industry, surfactants like polysorbates are commonly used as additives (excipients) to mitigate these undesirable interfacial exposures. However, polysorbates, the most prevalent choice, have recognized limitations in terms of polydispersity, purity, and stability, prompting the exploration of alternative excipients. The present study identifies poly(N-isopropylacrylamide)-poly(ethylene glycol) (PNIPAM-PEG) block copolymers as a promising alternative to polysorbates. Due to its stronger affinity for the air-water interface, PNIPAM-PEG significantly outperforms polysorbates in enhancing protein stability. This claim is supported by results from multiple tests. Accelerated dynamic light scattering (DLS) experiments demonstrate PNIPAM-PEG's exceptional efficacy in preserving IgG stability against surface-induced aggregation, surpassing conventional polysorbate excipients (Tween 80 and Tween 20) under high-temperature conditions. Additionally, circular dichroism (CD) spectroscopy results reveal conformational alterations associated with aggregation, with PNIPAM-PEG consistently demonstrates a greater protective effect by mitigating negative shifts at λ ≅ 220 nm, indicative of changes in secondary structure. Overall, this study positions PNIPAM-PEG as a promising excipient for antibody therapeutics, facilitating the development of more stable and effective biopharmaceuticals.

2024-06-01·Archives of Toxicology

The thrombopoietin mimetic JNJ-26366821 reduces the late injury and accelerates the onset of liver recovery after acetaminophen-induced liver injury in mice

Article

作者: Jaeschke, Hartmut ; Adelusi, Olamide B ; Ramachandran, Anup ; Akakpo, Jephte Y ; Sadaff, Ejaz ; Eichenbaum, Gary

Acetaminophen (APAP)-induced hepatotoxicity is comprised of an injury and recovery phase. While pharmacological interventions, such as N-acetylcysteine (NAC) and 4-methylpyrazole (4-MP), prevent injury there are no therapeutics that promote recovery. JNJ-26366821 (TPOm) is a novel thrombopoietin mimetic peptide with no sequence homology to endogenous thrombopoietin (TPO). Endogenous thrombopoietin is produced by hepatocytes and the TPO receptor is present on liver sinusoidal endothelial cells in addition to megakaryocytes and platelets, and we hypothesize that TPOm activity at the TPO receptor in the liver provides a beneficial effect following liver injury. Therefore, we evaluated the extent to which TPOm, NAC or 4-MP can provide a protective and regenerative effect in the liver when administered 2 h after an APAP overdose of 300 mg/kg in fasted male C57BL/6J mice. TPOm did not affect protein adducts, oxidant stress, DNA fragmentation and hepatic necrosis up to 12 h after APAP. In contrast, TPOm treatment was beneficial at 24 h, i.e., all injury parameters were reduced by 42-48%. Importantly, TPOm enhanced proliferation by 100% as indicated by PCNA-positive hepatocytes around the area of necrosis. When TPOm treatment was delayed by 6 h, there was no effect on the injury, but a proliferative effect was still evident. In contrast, 4MP and NAC treated at 2 h after APAP significantly attenuated all injury parameters at 24 h but failed to enhance hepatocyte proliferation. Thus, TPOm arrests the progression of liver injury by 24 h after APAP and accelerates the onset of the proliferative response which is essential for liver recovery.

100 项与 Pegylated thrombopoietin mimetic peptide 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
贫血	临床2期	-	Johnson & Johnson	-
血小板减少症	临床2期	-	Johnson & Johnson	-
急性髓性白血病	临床前	美国	Montefiore Medical Center	2019-05-26
急性髓性白血病	临床前	美国	Janssen Pharmaceuticals, Inc.	2019-05-26
骨髓增生异常综合征	临床前	美国	Montefiore Medical Center	2019-05-26
骨髓增生异常综合征	临床前	美国	Janssen Pharmaceuticals, Inc.	2019-05-26