Delving into the Latest Updates on SU-MI-2 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

SU-11274, SU-MI-2

Target

MST1R x c-Met

Action

inhibitors

Mechanism

MST1R inhibitors(Macrophage-stimulating protein receptor inhibitors), c-Met inhibitors(Hepatocyte growth factor receptor inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Originator Organization

Sugen, Inc.

Active Organization

Institut National de la Santé et de la Recherche Médicale

Inactive Organization

Sugen, Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Methylation processes in different molecular contexts (DNA, RNA, and histones) are controlled by different regulatory factors and serve as critical determinants in cancer development. However, the mechanistic links between these epigenetic modifications during malignant transformation, metastasis, disease relapse, and therapeutic resistance remain incompletely understood. In this research, we investigated the transcriptional and genetic alterations of regulators associated with 3 major types of methylation modifications in clear cell renal cell carcinoma. Utilizing ChIP/MeRIP-seq and 450K methylation array data, we identified genes regulated by multiple methylation modifications and constructed a scoring model to quantify the methylation patterns for each patient. Our findings indicate that patients with a low score may be more likely to respond to immunotherapy, whereas patients with a high score may be more sensitive to targeted therapy, such as RITA, Pazopanib, Irlotinib, SU-11274, BRD-K16762525, and FCCP. In conclusion, the score model can serve as a valuable biomarker to guide clinical selection of immunotherapy and targeted drugs and help to improve personalized clear cell renal cell carcinoma treatment.

18 Sep 2024·BRITISH JOURNAL OF DERMATOLOGY

Using network pharmacology to discover potential drugs for hypertrophic scars

Article

Author: Li, Xiu ; Yu, Qian ; Xiao, Ran ; Wang, Lianzhao ; Li, Chen ; Zhang, Yi ; Wang, Qian ; Liu, Yue ; Yang, Zhigang ; Lv, Xiaoyan ; Fu, Xin

Abstract:

Background:

Hypertrophic scarring is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation. Existing drugs have not achieved satisfactory therapeutic effects.

Objectives:

To explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for their treatment.

Methods:

Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model.

Results:

WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, the transforming growth factor (TGF)-β signalling pathway and other biologic pathways. Integrin β1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and profibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA can also inhibit mouse scar hyperplasia.

Conclusions:

ITGB1 and TGF-β signalling pathways are important for hypertrophic scar formation. Crizotinib could be a potential treatment drug for hypertrophic scars.

18 May 2024·International Journal of Ophthalmology

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

Article

Author: Wang, Tong ; Yuan, Wen-Ting ; Pan, Xiao-Yan ; Zhou, Si-Rui ; Chen, Xiao-Dong

AIM: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors. METHODS: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro. Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay. RESULTS: HGF increased ARPE-19 cells’ viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins. CONCLUSION: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

100 Deals associated with SU-MI-2

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Preclinical	France	Institut National de la Santé et de la Recherche Médicale	20 Nov 2009
Neoplasms	Discovery	United States	Sugen, Inc.	-