Delving into the Latest Updates on Propagermanium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

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

+ [7]

Target

CCL2

Mechanism

CCL2 inhibitors(C-C motif chemokine 2 inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System DisordersNeoplasms+ [1]

Active Indication

Hepatitis BBreast Cancer

Inactive Indication-

Originator Organization

Sanwa Kagaku Kenkyusho Co., Ltd.

Active Organization

Sanwa Kagaku Kenkyusho Co., Ltd.

Kyushu University

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (01 Jul 1994),

Hepatitis B

RegulationOrphan Drug (EU)

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Structure

Molecular FormulaC6H10Ge2O7

InChIKeyXEABSBMNTNXEJM-UHFFFAOYSA-N

CAS Registry12758-40-6

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.

Start Date08 Nov 2018

Sponsor / Collaborator

Dimerix Bioscience Pty Ltd.

[+1]

100 Clinical Results associated with Propagermanium

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100 Translational Medicine associated with Propagermanium

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100 Patents (Medical) associated with Propagermanium

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45

Literatures (Medical) associated with Propagermanium

01 Jul 2020·Endocrinology, Diabetes & Metabolism

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

Article

Author: 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.

01 Mar 2020·Cancer ScienceQ2 · MEDICINE

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

Q2 · MEDICINE

ArticleOA

Author: 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.

01 Jan 2020·The FASEB JournalQ2 · BIOLOGY

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

Q2 · BIOLOGY

Article

Author: 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 Deals associated with Propagermanium

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External Link

KEGG	Wiki	ATC	Drug Bank
D01626	Propagermanium	V09X	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis B	JP	Sanwa Kagaku Kenkyusho Co., Ltd.	01 Jul 1994

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Preclinical	JP	Kyushu University	01 Jul 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ATS2023	Not Applicable	Fibrosis	-	Nintedanib	hnspsnnfdl(wafpqzwfcm) = PET showed significant lung uptake in both models at day 14 cjlbkdttjq (qjfdznzele ) View more	-	21 May 2023
				Propagermanium