Delving into the Latest Updates on Medific Co., Ltd. with Synapse

Overview

Tags

Neoplasms

Nervous System Diseases

Other Diseases

Exosomes

Small molecule drug

Chemical drugs

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	4
Nervous System Diseases	4

Top 5 Drug Type	Count

Exosomes	3
Small molecule drug	1
Chemical drugs	1

Top 5 Target	Count

SREBF1(Sterol regulatory element binding transcription factor 1)	1

2038 Background: Glioblastoma (GBM) is an incurable cancer. Patients are subjected to inevitable death by recurrence after the standard treatment, temozolomide (TMZ) and irradiation. Having the tumor-initiating ability, GBM cancer stem cells (GSCs) resist standard therapy and give rise to recurrent tumors; however, no GSC-targeted treatment has proven its efficacy in clinical trials. Therefore, we sought to discover the vulnerability of GSCs and develop a novel targeted therapy to combine with TMZ, which will enable the complete treatment of GBM without the risk of relapse. Methods: We assessed the datasets of GBM patients and patient-derived GSCs to discover the signaling pathways enriched in GSCs that are specifically sensitive to dysregulation. We conducted transcriptomic, metabolomic and cellular assays to verify the essentiality of the pathway in GSCs and to find the target suitable for disturbing the pathway pharmacologically. Through the chemical library screening and chemical optimization, we developed a novel compound that specifically degrades the target. We validated the on-target specificity and pharmacokinetic (PK) properties through biological and pharmacological studies. We verified the anti-cancer efficacy in combination with TMZ using the GBM orthotopic xenograft mouse model and evaluated the safety and toxicity by non-clinical assessments. Results: Unbiased analysis using the datasets of patients and GSCs revealed that ABCA3-related lipid metabolism is enriched in GSCs compared to non-GSCs. ABCA3 knockdown caused the disturbance in lipid metabolic homeostasis, leading to a decrease in the sterol-regulatory element binding protein 1 (SREBP1) activity to suppress the tumor-initiating capacity of the GSCs. We developed MFC0101, a novel small molecular compound to target the SREBP1 signaling pathway. MFC0101 specifically engages the SREBP cleavage-activating protein (SCAP), which binds to and stabilizes the SREBP1 protein, to block the protein-protein interaction between SCAP and SREBP1, inducing the degradation of SREBP1. MFC0101 displayed favorable PK profiles, such as high oral bioavailability (greater than 50% in dogs, rats, and mice) and blood-brain barrier permeability (brain-to-plasma ratio of 0.543 based on exposure in mice). MFC0101 showed no adverse events, even at the dose level required to reach maximal systemic exposure in the 28-day toxicity study in rats, and no geno- and cardiovascular toxicities. Notably, MFC0101, combined with TMZ, showed greater efficacy than TMZ alone in the GBM mouse model; 87.5% and 100% displayed complete remission of the tumor after the treatment of medium and high dose levels of MFC0101, respectively (n ≥ 8 per group). Conclusions: MFC0101, the first-in-class SREBP1-targeted degrader, demonstrates its outstanding preclinical efficacy in synergy with TMZ and reasonable safety as a promising GBM treatment.

Cell Death & Disease

ID1high/activin Ahigh glioblastoma cells contribute to resistance to anti-angiogenesis therapy through malformed vasculature

Article

Author: Choi, Sang-Hun ; Kim, Yoonji ; Jang, Junseok ; Kim, Hyojin ; Park, Cheol Gyu ; Kim, Hyunggee ; Lee, Seon Yong

AbstractAlthough bevacizumab (BVZ), a representative drug for anti-angiogenesis therapy (AAT), is used as a first-line treatment for patients with glioblastoma (GBM), its efficacy is notably limited. Whereas several mechanisms have been proposed to explain the acquisition of AAT resistance, the specific underlying mechanisms have yet to be sufficiently ascertained. Here, we established that inhibitor of differentiation 1 (ID1)high/activin Ahigh glioblastoma cell confers resistance to BVZ. The bipotent effect of activin A during its active phase was demonstrated to reduce vasculature dependence in tumorigenesis. In response to a temporary exposure to activin A, this cytokine was found to induce endothelial-to-mesenchymal transition via the Smad3/Slug axis, whereas prolonged exposure led to endothelial apoptosis. ID1 tumors showing resistance to BVZ were established to be characterized by a hypovascular structure, hyperpermeability, and scattered hypoxic regions. Using a GBM mouse model, we demonstrated that AAT resistance can be overcome by administering therapy based on a combination of BVZ and SB431542, a Smad2/3 inhibitor, which contributed to enhancing survival. These findings offer valuable insights that could contribute to the development of new strategies for treating AAT-resistant GBM.

Cell Death & Disease

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion

Article

Author: Park, Sehyeon ; Kim, Yoonji ; Ham, Seok Won ; Park, Jong-Whi ; Hong, Nayoung ; Kim, Eun-Jung ; Kim, Hyunggee ; Jang, Junseok ; Kim, Jun-Kyum ; Kim, Jung Yun ; Kim, Sung-Chan ; Kim, Sung-Ok

AbstractJagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-β signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-β signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.

100 Deals associated with Medific Co., Ltd.

Login to view more data

100 Translational Medicine associated with Medific Co., Ltd.

Login to view more data

Corporation Tree

Boost your research with our corporation tree data.

login

or

view full example data

Boost your research with our corporation tree data.

Pipeline

Pipeline Snapshot as of 05 Aug 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

5

Login to view more data

Current Projects

Drug(Targets)	Indications	Global Highest Phase

MFC-0201	Glioblastoma More	Preclinical
MFC-0301	Glioblastoma More	Preclinical
MFC-0103	Alzheimer Disease More	Preclinical
MFC-0102	Solid tumor More	Preclinical
MFC-0101 ( SREBF1 )	Glioblastoma More	Preclinical