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)

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100 Clinical Results associated with SB-505124

100 Translational Medicine associated with SB-505124

100 Patents (Medical) associated with SB-505124

Literatures (Medical) associated with SB-505124

01 Nov 2024·Acta Crystallographica Section F Structural Biology Communications

Human transforming growth factor β type I receptor in complex with kinase inhibitor SB505124

Article

Author: Landström, Maréne ; Rodriguez Buitrago, Jhon A ; Wolf-Watz, Magnus

The crystal structure of the intracellular domain of transforming growth factor β type I receptor (TβR1) in complex with the competitive inhibitor SB505124 is presented. The study provides insights into the structure and function of TβR1 in complex with SB505124, and as such offers molecular-level understanding of the inhibition of this critical signalling pathway. The potential of SB505124 as an avenue for therapy in cancer treatment is discussed on basis of the results.

01 Apr 2024·Cell Biochemistry and Function

Adenosine increases PD‐L1 expression in mesenchymal stromal cells derived from cervical cancer through its interaction with A_2AR/A_2BR and the production of TGF‐β1

Article

Author: Torres-Pineda, Daniela Berenice ; Montesinos-Montesinos, Juan José ; Sánchez-Torres, Luvia Enid ; Weiss-Steider, Benny ; Marín-Aquino, Luis Antonio ; López-Santiago, Ruben ; Mora-García, María de Lourdes ; Monroy-García, Alberto ; Don-López, Christian Azucena ; García-Rocha, Rosario ; Moreno-Lafont, Martha C ; Hernández-Montes, Jorge

AbstractMesenchymal stromal cells (MSCs) together with malignant cells present in the tumor microenvironment (TME), participate in the suppression of the antitumor immune response through the production of immunosuppressive factors, such as transforming growth factor beta 1 (TGF‐β1). In previous studies, we reported that adenosine (Ado), generated by the adenosinergic activity of cervical cancer (CeCa) cells, induces the production of TGF‐β1 by interacting with A2AR/A2BR. In the present study, we provide evidence that Ado induces the production of TGF‐β1 in MSCs derived from CeCa tumors (CeCa‐MSCs) by interacting with both receptors and that TGF‐β1 acts in an autocrine manner to induce the expression of programmed death ligand 1 (PD‐L1) in CeCa‐MSCs, resulting in an increase in their immunosuppressive capacity on activated CD8+ T lymphocytes. The addition of the antagonists ZM241385 and MRS1754, specific for A2AR and A2BR, respectively, or SB‐505124, a selective TGF‐β1 receptor inhibitor, in CeCa‐MSC cultures significantly inhibited the expression of PD‐L1. Compared with CeCa‐MSCs, MSCs derived from normal cervical tissue (NCx‐MSCs), used as a control and induced with Ado to express PD‐L1, showed a lower response to TGF‐β1 to increase PD‐L1 expression. Those results strongly suggest the presence of a feedback mechanism among the adenosinergic pathway, the production of TGF‐β1, and the induction of PD‐L1 in CeCa‐MSCs to suppress the antitumor response of CD8+ T lymphocytes. The findings of this study suggest that this pathway may have clinical importance as a therapeutic target.

01 Jul 2023·Cell biochemistry and function

Inhibition of TGF-β type I receptor by SB505124 down-regulates osteoblast differentiation and mineralization of human mesenchymal stem cells.

Article

Author: Almuraikhi, Nihal

Numerous signaling pathways are well-known in osteoblastic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), including transforming growth factor-beta (TGF-β) signaling pathway, which sends signals through specific type I and II serine/threonine kinase receptors. However, the key role of TGF-β signaling during bone formation and remodeling is yet to be studied. A TGF-β type I receptor inhibitor, SB505124, discovered through a screening of a small molecule library for their effect of osteoblast differentiation of hBMSCs. Alkaline phosphatase quantification and staining were tested as indicators of osteoblastic differentiation and Alizarin red staining was tested as an indicator of in vitro mineralization. Changes in gene expressions were assessed using qRT-PCR. SB505124 showed significant inhibition of the osteoblast differentiation of hBMSCs, as confirmed by reduced alkaline phosphatase, in vitro mineralization, and downregulation of osteoblast-associated gene expression. To further understand the molecular mechanisms involved in the inhibition of the TGF-β type I receptor, we assessed the effects on signature genes of several signaling pathways identified in the osteoblast differentiation of hBMSCs. SB505124 downregulated gene expression of many genes linked to osteoblast-related signaling pathways including TGF-β, insulin, focal adhesion, Notch, Vitamin D, interleukin (IL)-6, osteoblast signaling, and cytokines and inflammatory. We report TGF-β type I receptor inhibitor (SB505124) is a potent inhibitor of osteoblastic differentiation of hBMSCs that could be a valuable innovative therapeutic tool to cure bone disorders with increased bone formation, besides its potential use to treat patients with cancer and fibrosis.

100 Deals associated with SB-505124

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