A First-in-human, Randomized, Double-blind, Parallel, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of B1344 by Subcutaneous Injection in Healthy Subjects

To evaluate the safety, tolerability, and immunogenicity of B1344 by single subcutaneous (s.c.) injection in healthy subjects

Start Date30 Aug 2022

Sponsor / Collaborator

Shanghai Tasly Pharmaceutical Co. Ltd.

100 Clinical Results associated with Recombinant pegylated human FGF21(Tasly Biopharmaceuticals)

100 Translational Medicine associated with Recombinant pegylated human FGF21(Tasly Biopharmaceuticals)

100 Patents (Medical) associated with Recombinant pegylated human FGF21(Tasly Biopharmaceuticals)

Literatures (Medical) associated with Recombinant pegylated human FGF21(Tasly Biopharmaceuticals)

01 Dec 2024·International Immunopharmacology

Fibroblast growth factor 21 attenuates pulmonary ischemia/reperfusion injury via inhibiting endoplasmic reticulum stress-induced ferroptosis though FGFR1/PPARδ signaling pathway

Article

Author: Ye, Xinqiao ; Huang, Xiuyun ; Huang, Jianming ; Xue, Jinping ; Li, Wei ; Pei, Fang ; Zhang, Liyan

BACKGROUNDAcute lung injury is a critical life-threatening complication of pulmonary and cardiac surgery with a high rate of morbidity and mortality. Fibroblast growth factor 21 (FGF21) has been reported to play an important role in protecting vital organs from damage. This study aims to investigate the potential protective role and mechanism of FGF21 in pulmonary ischemia/reperfusion (I/R)-induced acute lung injury.METHODSA pulmonary epithelial cell line was treated with hypoxia/regeneration (H/R) in vitro and a mouse model of acute lung injury was induced with pulmonary I/R in vivo. Lung injury after pulmonary I/R was compared between FGF21-konckout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect.RESULTSCirculating levels of FGF21 in mice with pulmonary I/R injury were significantly higher than in those without pulmonary I/R injury. Lung injury was aggravated in FGF21-KO mice compared with WT mice and the administration of FGF21 alleviated lung injury in mouse treated with I/R and pulmonary epithelial cell injury treated with H/R. FGF21 treatment decreased endoplasmic reticulum (ER) stress, Fe²⁺ and lipid reactive oxygen species (ROS) contents and GPX4 expression and increased PTGS2 levels. Mechanistically, FGF21 upregulated the expression of FGFR1 and PPARδ, ameliorated ER stress and ER stress induced-ferroptosis. Furthermore, FGF21 increased the expression level of PPARδ in pulmonary epithelial cell exposed to H/R, which was inhibited by FGFR1 inhibitor (PD173074). The protective effects of FGF21 were abolished by co-treatment with PPARδ inhibitor (GSK0660), indicating FGF21 attenuated ER stress-induced ferroptosis by dependent on FGFR1/PPARδ signaling pathway.CONCLUSIONOur study reveals that FGF21 protects against pulmonary I/R injury via inhibiting ER stress-induced ferroptosis though FGFR1/PPARδ signaling pathway. Boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for pulmonary IRI.

01 Nov 2024·Biochemical and Biophysical Research Communications

Fibroblast growth factor-21 potentiates the stimulatory effects of 1,25-dihydroxyvitamin D3 on transepithelial calcium transport and TRPV6 Ca2+ channel expression

Article

Author: Charoenphandhu, Narattaphol ; Teerapornpuntakit, Jarinthorn ; Nammultriputtar, Ketsaraporn ; Chankamngoen, Wasutorn ; Chaichanan, Jirapan ; Wongdee, Kannikar ; Thammayon, Nithipak ; Svasti, Saovaros ; Supcharoen, Promsup ; Teerapo, Kittitat ; Suntornsaratoon, Panan ; Rodrat, Mayuree ; Kitiyanant, Narisorn ; Panupinthu, Nattapon ; Donpromma, Natthida

Fibroblast growth factor (FGF)-21 is a salient liver-derived endocrine regulator for metabolism of glucose and triglyceride as well as bone remodeling. Previously, certain peptides in the FGF family have been shown to modulate calcium absorption across the intestinal epithelia. Since FGF21 receptor, i.e., FGF receptor-1, is abundantly expressed in the enterocytes, there was a possibility that FGF21 might exert direct actions on the intestine. Herein, a large-scale production of recombinant FGF21 at the multi-gram level was developed in order to minimize variations among various batches. In the oral glucose tolerance test, recombinant FGF21 was found to reduce plasma glucose levels in mice fed high-fat diet. A series of experiments applying radioactive tracer ⁴⁵Ca in Ussing chamber showed that FGF21 potentiated the stimulatory effect of low-dose 1,25-dihydroxyvitamin D₃ [10 nM 1,25(OH)₂D₃] on the transepithelial calcium transport across intestinal epithelium-like Caco-2 monolayer. FGF21 + 1,25(OH)₂D₃ also decreased transepithelial resistance, but had no effect on epithelial potential difference or short-circuit current. Furthermore, 1,25(OH)₂D₃ alone upregulated the Caco-2 mRNA expression of the major apical calcium channels, i.e., transient receptor potential vanilloid subfamily member 6 (TRPV6), which was further elevated by a combination of FGF21 and 1,25(OH)₂D₃, consistent with the upregulated TRPV6 protein expression in enterocytes of FGF21-treated mice. However, FGF21 was without effects on the mRNA expression of voltage-gated calcium channel 1.3, calbindin-D_9k, plasma membrane Ca²⁺-ATPase 1b, claudin-12 or claudin-15. In conclusion, FGF21 did exert a direct action on the intestinal epithelial cells by potentiating the 1,25(OH)₂D₃-enhanced calcium transport, presumably through the upregulation of TRPV6 expression.

01 Nov 2024·Redox Biology

Lycopene alleviates age-related cognitive deficit via activating liver-brain fibroblast growth factor-21 signalling

Article

Author: Li, Li ; Shen, Yuqi ; Qiu, Fubin ; Wang, Jia ; Li, Lu

Brain function is linked with many peripheral tissues, including the liver, where hepatic fibroblast growth factor 21 (FGF21) mediates communication between the liver and brain. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, we investigated the effects of LYC on age-related memory impairment and the relative contribution of liver-brain FGF21 signaling in these process. The results showed that after treatment with LYC for 3 months, brain aging and age-related cognitive deficits were effectively managed. In addition, LYC ameliorated neuronal degeneration, mitochondrial dysfunction and synaptic damage, and promoted synaptic vesicle fusion in 18-month-old mice. Notably, LYC activated liver-brain FGF21 signalling in aging mice. Whereas all these central effects of LYC were negated by blocking FGF21 via i. v. injection of adeno-associated virus in aging mice. Furthermore, recombinant FGF21 elevated mitochondrial ATP levels and enhanced synaptic vesicle fusion in mouse hippocampal HT-22 cells, which promoted neurotransmitter release. Additionally, we co-cultured hepatocytes and neurons in Transwell and found that LYC enhanced hepatocytes' support for neurons. This support included improved cell senescence, enhanced mitochondrial function, and increased axon length in co-cultured neurons. In conclusion, LYC protects against age-related cognitive deficit, partly explained by activating liver-brain FGF21 signalling, hence promoting neurotransmitters release via increasing mitochondrial ATP levels and enhancing synaptic vesicle fusion. These findings revealed that FGF21 could be a potential therapeutical target in nutritional intervention strategies to improve cognitive damage caused by aging and age-related neurodegenerative diseases.

100 Deals associated with Recombinant pegylated human FGF21(Tasly Biopharmaceuticals)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Nonalcoholic Steatohepatitis	Phase 1	US	Shanghai Tasly Pharmaceutical Co. Ltd.	30 Aug 2022
Diabetes Mellitus, Type 2	IND Approval	CN	Shanghai Tasly Pharmaceutical Co. Ltd.	16 Sep 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Recombinant pegylated human FGF21(Tasly Biopharmaceuticals)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation