丙帕诺(Propagermanium) - 药物靶点：CCL2_在研适应症：乙型肝炎，乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

3-Oxygermylpropionic acid polymer、Propagermanium (JAN)、Proxigermanium

+ [7]

靶点

CCL2

作用机制

CCL2抑制剂(C-C基序趋化因子-2抑制剂)

治疗领域

感染消化系统疾病肿瘤+ [1]

在研适应症

乙型肝炎乳腺癌

非在研适应症-

原研机构

Sanwa Kagaku Kenkyusho Co., Ltd.

在研机构

Sanwa Kagaku Kenkyusho Co., Ltd.

Kyushu University

非在研机构-

最高研发阶段批准上市

首次获批日期

日本 (1994-07-01),

乙型肝炎

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

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结构

分子式C6H10Ge2O7

InChIKeyXEABSBMNTNXEJM-UHFFFAOYSA-N

CAS号12758-40-6

关联

9

项与丙帕诺相关的临床试验

ACTRN12618000910202 / Completed临床2期

A Phase 2a, Double-blind, Randomised, Placebo-Controlled, Crossover Study Evaluating the Safety and Efficacy of Propagermanium in Patients with Primary Focal Segmental Glomerulosclerosis (FSGS) who are receiving Irbesartan

开始日期2018-11-20

申办/合作机构

Dimerix Ltd.

ACTRN12618000982213 / Completed临床2期

A Phase 2, Double-blind, Randomised, Placebo-Controlled, Crossover Study Evaluating the Safety and Efficacy of Propagermanium in Patients with Diabetic Kidney Disease (DKD) who are Receiving Irbesartan

开始日期2018-11-19

申办/合作机构

Dimerix Ltd.

NCT03649152 / Completed临床2期

A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Evaluating the Safety and Efficacy of Propagermanium in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS) Who Are Receiving Irbesartan

This study will be evaluating the safety and efficacy of propagermanium for the treatment of participants with FSGS who are already taking irbesartan by:
monitoring symptoms that participants may experience while on the study,
measuring levels of protein in participant's urine and kidney function during the course of the study,
measuring the levels of propagermanium and irbesartan that enters into participant's urine and blood, and
comparing the propagermanium outcomes to participants' pre-study and placebo outcomes.
Eligible participants will randomly be assigned to one of two arms to receive both the propagermanium and placebo in different orders as follows, either:
Treatment Period 1 taking a propagermanium capsule twice a day for 16 weeks, followed by a six week washout period followed by Treatment Period 2 taking a placebo capsule twice a day for 16 weeks.
OR Treatment Period 1 taking a placebo capsule twice a day for 16 weeks, followed by a six week washout period followed by Treatment Period 2 taking a propagermanium capsule twice a day for 16 weeks.

开始日期2018-11-08

申办/合作机构

Dimerix Bioscience Pty Ltd.

[+1]

100 项与丙帕诺相关的临床结果

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100 项与丙帕诺相关的转化医学

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100 项与丙帕诺相关的专利（医药）

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45

项与丙帕诺相关的文献（医药）

2020-07-01·Endocrinology, Diabetes & Metabolism

Propagermanium administration for patients with type 2 diabetes and nephropathy: A randomized pilot trial

Article

作者: Kakuda, Hirokazu ; Koshino, Yoshitaka ; Sakai, Norihiko ; Takasawa, Kazuya ; Kitagawa, Kiyoki ; Shimizu, Miho ; Ikeda, Kenzo ; Okumura, Toshiya ; Toyama, Tadashi ; Hisada, Yukimasa ; Kobayashi, Motoo ; Wada, Takashi ; Hara, Akinori ; Iwata, Yasunori ; Hamaguchi, Erika

SummaryAimsWe assessed the potential efficacy and safety of propagermanium (PG), an organic compound that inhibits the C–C chemokine receptor type 2, administration in patients with type 2 diabetes and nephropathy. Furthermore, we assessed the feasibility of future studies.Materials and methodsWe recruited patients from nine medical institutions in Japan for this randomized, open‐label, parallel two‐arm pilot trial. Inclusion criteria were diagnosis of type 2 diabetes, age 30‐75 years, dipstick proteinuria of ≥1+ or urinary albumin‐to‐creatinine ratio (UACR) of ≥30 mg/g and estimated glomerular filtration rate of ≥30 mL/min/1.73 m2. Patients were randomly assigned (1:2) using a minimization algorithm to either continuing usual care or concomitant administration of 30 mg PG per day for 12 months. The primary outcome was the change in UACR from baseline to 12 months. We also collected safety information for all patients who received at least one dose of PG.ResultsWe enrolled 29 patients, 10 were assigned to continue usual care and 19 to receive PG. Changes in UACR by PG in addition to the usual care were 25.0% (95% CI −20.4%, 96.5%, P = .33). No severe adverse events or renal events were observed during the study.ConclusionAlthough the treatment with PG was generally well tolerated, the dosage of 30 mg/d for 12 months did not reduce albuminuria when used in addition to usual care in patients with type 2 diabetes and nephropathy. Efficacy of PG should be verified in future definitive trials.

2020-03-01·Cancer Science2区 · 医学

Phase I dose‐escalation trial to repurpose propagermanium, an oral CCL2 inhibitor, in patients with breast cancer

2区 · 医学

ArticleOA

作者: Kitagawa, Dai ; Masuda, Takaaki ; Mimori, Koshi ; Kogawa, Takahiro ; Nakanishi, Yoichi ; Nakayama, Keiichi I. ; Hayashi, Naoki ; Jomori, Takahito ; Ohno, Shinji ; Noda, Miwa

AbstractThe formation of premetastatic niches creates a fertile environment for the seeding of disseminated cancer cells in selected secondary organs. This is crucial for the development of metastasis in various malignancies, including breast cancer (BC). We previously reported that the loss of FBXW7 in bone marrow‐derived stromal cells promoted cancer metastasis by increasing the production of the chemokine CCL2, which attracts myeloid‐derived suppressor cells and macrophages to the premetastatic niche. Furthermore, treatment with the CCL2 inhibitor propagermanium (PG), which has been used in Japan as a therapeutic agent against chronic hepatitis B, was shown to block the enhancement of metastasis in FBXW7‐deficient mice through inhibiting the formation of premetastatic niches. Here, we describe a phase I dose‐escalation study of PG used as an antimetastatic drug for perioperative patients with primary BC. The primary end‐point was the percentage of patients who experience dose‐limiting toxicity. Twelve patients were enrolled in the study. Dose‐limiting toxicity was not observed, and the maximum dose was determined to be 90 mg/body/day. The serum concentrations of PG were nearly within the normal range in all observation days. We observed an inverse correlation between FBXW7 mRNA levels in blood and the serum concentrations of CCL2 and interleukin (IL)‐6, in agreement with our previous mouse model. Also, IL‐6 was downregulated in a PG dose‐dependent manner, as observed in mice. Thus, PG was given safely and it is expected to have antimetastatic potential in BC. This trial is registered in the UMIN Clinical Trials Registry as UMIN000022494.

2020-01-01·The FASEB Journal2区 · 生物学

Chemokine CCL2 contributes to BBB disruption via the p38 MAPK signaling pathway following acute intracerebral hemorrhage

2区 · 生物学

Article

作者: Guo, Fuyou ; Lin, Yazhou ; Gao, Qiang ; Wang, Fang ; Xu, Dingkang ; Wei, Qingjie ; Lei, Shixiong ; Wang, Guoqing

AbstractIntracerebral hemorrhage (ICH) remains a devastating type of stroke that lacks an effective treatment. Recent evidence has demonstrated that CCL2 is involved in the blood‐brain barrier (BBB) disruption and propagermanium (PG) as a CCL2 receptor inhibitor is neuroprotective in ischemic stroke. However, whether PG therapy exert effective role in acute ICH still unclear. In this study, our goal was to investigate the potential role of CCL2 and the effects of PG in ICH. Differentially expressed RNAs including CCL2 were detected in human ICH. CCL2 and the activation of p‐p38 MAPK and AQP4 expression were analyzed in rats after ICH. Brain water content and BBB integrity as well as neurological function were also examined after PG administration. In addition, the mechanism by which CCL2‐mediated BBB injury was further investigated by cell coculture. Our findings showed that PG could effectively reduce brain edema and improve neurobehavioral functions. p‐p38 MAPK and AQP4 expression were significantly inhibited by PG in vivo and in vitro. To the best of our knowledge, this is the first demonstration of PG in neuroprotecting the BBB integrity by inhibition of CCL2‐CCR2‐p38 MAPK pathway following ICH, targeting CCL2 could be developed as a novel treatment for hemorrhagic stroke.

100 项与丙帕诺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01626	丙帕诺	V09X	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
乙型肝炎	日本	Sanwa Kagaku Kenkyusho Co., Ltd.	1994-07-01

未上市

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
乳腺癌	临床前	日本	Kyushu University	2017-07-01

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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


ATS2023	N/A	纤维化	-	Nintedanib	獵製鬱醖齋蓋鬱糧鹽艱(鏇積窪餘鹽廠網蓋艱觸) = PET showed significant lung uptake in both models at day 14 鹽衊襯餘網醖鏇膚齋鹽 (淵鹹廠願襯鹽願糧鹽遞 ) 更多	-	2023-05-21
				Propagermanium