ALK4 inhibitors(activin A receptor type 1B inhibitors), ALK5 inhibitors(Transforming growth factor beta receptor 1 inhibitors), ALK7 inhibitors(activin A receptor type 1C inhibitors)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H16N4O3

InChIKeyFHYUGAJXYORMHI-UHFFFAOYSA-N

CAS Registry301836-41-9

100 Clinical Results associated with SB-431542

100 Translational Medicine associated with SB-431542

100 Patents (Medical) associated with SB-431542

1,191

Literatures (Medical) associated with SB-431542

01 Jan 2025·Biofabrication

A microvascularized in vitro liver model for disease modeling and drug discovery

Article

Author: Caro Torregrosa, Manuel Caro ; Dinkelberg, Roelof ; Kortekaas, Nienke ; Torregrosa, Manuel Caro ; Kurek, Dorota ; Bircsak, Kristin ; Hagens, Tessa Maria Sophia ; Bonanini, Flavio ; Treillard, Stéphane ; van Duinen, Vincent ; Vulto, Paul ; Hagens, Tessa M S

AbstractDrug discovery for complex liver diseases faces alarming attrition rates. The lack of non-clinical models that recapitulate key aspects of liver (patho)-physiology is likely contributing to the inefficiency of developing effective treatments. Of particular notice is the common omission of an organized microvascular component despite its importance in maintaining liver function and its involvement in the development of several pathologies. Increasing the complexity of in vitro models is usually associated with a lack of scalability and robustness which hinders their implementation in drug development pipelines. Here, we describe a comprehensive liver microphysiological system comprising stellates, liver-derived endothelial cells and hepatocytes conceived within a scalable and automated platform. We show that endothelial cells self-organize in a microvascular network when co-cultured with stellates in a hydrogel. In a tri-culture, hepatocytes polarize accordingly, with a basolateral side facing blood vessels and an apical side facing bile-canaliculi-like structures. Stellates interact and surround the hollow microvessels. Steatosis was induced by exogenous administration of fatty acids which could be prevented by co-administration of firsocostat. Administration of TGF-β resulted in an activated stellate cells phenotype which could be prevented by the co-administration of SB-431542. The model was implemented on a microtiter plate format comprising 64 chips which enabled the development of a fully automated, multiplexed fibrosis assay with a robust Z’ factor suitable for high-throughput applications.

31 Dec 2024·Experimental Lung Research

Leucine rich α2 glycoprotein 1 derived from malignant pleural mesothelioma cells facilitates macrophage M2 phenotypes

Article

Author: Pei, Wenjing ; Mo, Rongliang ; Zhao, Dahai ; Su, Yi ; Gu, Wenhui ; Li, Xinru ; Liu, Yanfei ; Wang, Dandan ; Ye, Jing ; Xu, Jiegou

Background: Macrophages constitute the main part of infiltrating immune cells in Malignant pleural mesothelioma (MPM) and abnormally high ratios of M2 macrophages are present in both pleural effusion and tissue samples of MPM patients. Whether MPM cells affect formation of M2 macrophages is poorly understood. In this study, we focused on identification of MPM-cells-derived soluble factors with M2-promoting effects. Methods: Media of malignant pleural mesothelioma cells were collected and soluble factors affecting macrophages were analyzed by mass spectrometry. TGF-β receptor inhibitor SB431542 was used as the entry point to explore the downstream mechanism of action by qRT-PCR, WB and immunofluorescence. Results: The serum-free culture media collected from the human MPM cells Meso1 and Meso2 significantly enhanced expression of the M2 signature molecules including IL-10, TGF-β and CD206 in the human macrophages THP-1, while the culture medium of the human MPM cells H2452 did not show such M2-promoting effects. Analysis of proteins by mass spectrometry and ELISA suggested that Leucine rich α2 glycoprotein 1(LRG1) was a potential candidate. LRG1 time- and dose-dependently increased expression of the M2 signature molecules, confirming its M2-promoting effects. Furthermore, LRG1's M2-promoting effects were reduced by the TGF-β receptor inhibitor SB431542, and LRG1 increased phosphorylation of Smad2, indicating that M2-promoting effects of LRG1 were via the TGF-β receptor/Smad2 signaling pathway. Conclusions: Our results provide a potential M2-promoting new member, LRG1, which contributes to the immune escape of MPM via the TGF-β receptor/Smad2 signaling pathway.

01 Nov 2024·iScience

Conversion of glioma cells into neuron-like cells by small molecules

Article

Author: Yi, Yongjun ; Wang, Xiangyu ; Lyu, Jun ; Mao, Chuxiao ; Xu, Ping ; Li, Zhizhong ; Wang, Qingsong ; Che, Wenqiang

Currently, researchers are exploring the conversion of astrocytes into functional mature neurons and gradually exploring the conversion of glioma into neurons. We report that SLCDS (SB431542, LDN193189, CHIR99021, DAPT, and SKL2001) has been shown to convert human glioma cells into mature neuron-like cells. The converted cells exhibited upregulation of DCX, TuJ1, MAP2, NeuN, and GAD67, while the expressions of EGFR, PDGFR, Ki67, and vimentin were inhibited. The nTFs, such as NeuroD1 and Sox2, were upregulated, along with TF genes associated with neurogenesis and tumor suppression. We have finally confirmed that overexpressing nTFs can induce the conversion of glioma cells into neuronal cells. This study demonstrates that SLCDS can activate the expression of nTFs in human glioma cells and induce the conversion of human glioma cells into neuron-like cells. Additionally, SLCDS inhibits the expressions of EGFR, PDGFR, Ki67, and Vimentin in gliomas. Our findings offer a potential approach for treating glioma.

100 Deals associated with SB-431542

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	US	GSK Plc	31 Jul 2002

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