Delving into the Latest Updates on SCC-31 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

mTORC1 x mTORC2

Mechanism

mTORC1 inhibitors(Mammalian target of Rapamycin (mTORC1) inhibitors), mTORC2 inhibitors(mTOR Complex 2 inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Advanced Malignant Solid NeoplasmHER2-negative breast cancerMetastatic breast cancer+ [1]

Inactive Indication

Advanced breast cancer

Originator Organization

Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

Active Organization

Fudan University

Shanghai Institute of Materia Medica Chinese Academy of Sci

Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure/Sequence

Molecular FormulaC26H30N6O3

InChIKeyLVPBYQVQBZLDAU-DZIBYMRMSA-N

CAS Registry1567915-38-1

To evaluate the safety, tolerability, pharmacokinetic characteristics and anti-tumor effects of LXI-15029 as a monotherapy in Chinese patients with advanced solid malignancies, and in combination with exemestane in Chinese postmenopausal patients with ER-positive, HER2-negative metastatic or locally advanced breast cancer

Start Date12 Jun 2017

Sponsor / Collaborator

Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

[+2]

NCT03125746

/ Unknown statusPhase 1

A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profiles and the Antitumor Activity of LXI-15029 Alone or in Combination With Exemestane at Single Ascending Dose and Multiple Ascending Doses in Chinese Patients With Advanced Malignant Solid Tumors

1. To evaluate the safety and tolerability of LXI-15029 in Chinese patients with advanced malignant solid tumors in monotherapy period, including confirmation of the maximum tolerated dose (MTD) of monotherapy. 2.To evaluate the safety and tolerability of LXI-15029 in Chinese postmenopausal patients with metastatic or locally advanced breast cancer with estrogen receptor (+) and human epidermal growth factor receptor 2 (-) in combined with Exemestane period , including confirmation of the maximum tolerated dose(MTD) of the combined therapy with Exemestane.

Start Date12 Jun 2017

Sponsor / Collaborator

Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

100 Clinical Results associated with SCC-31

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100 Translational Medicine associated with SCC-31

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100 Patents (Medical) associated with SCC-31

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10

Literatures (Medical) associated with SCC-31

01 Nov 2024·Antiviral Research

Large-scale deep learning identifies the antiviral potential of PKI-179 and MTI-31 against coronaviruses

Article

Author: Kurmasheva, Naziia ; Thielke, Anne L. ; van der Horst, Demi ; Chorošajev, Vladimir ; Silva da Costa, Leandro ; Belouzard, Sandrine ; Carter-Timofte, Madalina E. ; Olagnier, David ; Hansen, Anne Louise ; Danneels, Adeline ; Carter-Timofte, Madalina E ; Beny, Cedric ; Thielke, Anne L ; Holm, Christian K. ; Holm, Christian K ; de Weber, Ivan

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global pandemic of Coronavirus Disease (2019) (COVID-19), underscoring the urgency for effective antiviral drugs. Despite the development of different vaccination strategies, the search for specific antiviral compounds remains crucial. Here, we combine machine learning (ML) techniques with in vitro validation to efficiently identify potential antiviral compounds. We overcome the limited amount of SARS-CoV-2 data available for ML using various techniques, supplemented with data from diverse biomedical assays, which enables end-to-end training of a deep neural network architecture. We use its predictions to identify and prioritize compounds for in vitro testing. Two top-hit compounds, PKI-179 and MTI-31, originally identified as Pi3K-mTORC1/2 pathway inhibitors, exhibit significant antiviral activity against SARS-CoV-2 at low micromolar doses. Notably, both compounds outperform the well-known mTOR inhibitor rapamycin. Furthermore, PKI-179 and MTI-31 demonstrate broad-spectrum antiviral activity against SARS-CoV-2 variants of concern and other coronaviruses. In a physiologically relevant model, both compounds show antiviral effects in primary human airway epithelial (HAE) cultures derived from healthy donors cultured in an air-liquid interface (ALI). This study highlights the potential of ML combined with in vitro testing to expedite drug discovery, emphasizing the adaptability of AI-driven approaches across different viruses, thereby contributing to pandemic preparedness.

01 Apr 2024·Applied Biochemistry and Biotechnology

Protective Autophagy Attenuates the Cytotoxicity of MTI-31 in Renal Cancer Cells by Activating the ERK Pathway

Article

Author: Liu, Rongzong ; Hu, Yun ; Hu, Jimeng ; Xu, Chenyang ; Zou, Lujia ; Zang, Yiwen ; Yang, Chen ; Xiong, Zuquan ; Dai, Meng-Shi ; Zhang, Wenye ; Wang, Hao

The mammalian target of rapamycin (mTOR) is a key regulatory molecular target to treat cancer, and MTI-31 is a potent mTOR inhibitory agent for the therapeutically target of the renal cell carcinoma (RCC). However, the therapeutic efficacy of MTI-31 is limited by multiple factors, including autophagy. MTI-31 can activate cells to generate autophagy, which may in turn indirectly affect cell proliferation and apoptosis. We aimed to observe changes in cell protective autophagy via the ERK pathway and explore the potential mechanism underlying drug resistance of RCC cells to MTI-31. Different concentrations of 786-O and RCC4 cells were co-cultured with MTI-31 for distinct durations. The result of autophagy marker detection by Western blot showed that MTI-31 could induce RCC cells to produce autophagy in a dose and time-dependent manner. After treating the RCC cells with the autophagy inhibitor chloroquine (CQ), CCK8 and Western blot assays demonstrated that CQ could effectively enhance cell apoptosis induced by MTI-31 and that the autophagy induced by MTI-31 was cytoprotective. In addition, CCK8 and Western blot demonstrated that MTI-31 exerted its effect by activating the ERK pathway rather than the JNK or p38 pathway. The use of the ERK inhibitor AZD6244 to block the ERK pathway could effectively promote cell apoptosis induced by MTI-31. AZD6244 attenuated the autophagy induced by MTI-31 and increased the cytotoxicity of MTI-31. Western blot also demonstrated that MTI-31-induced autophagy was mediated by the downstream regulators of ERK pathways, including Beclin-1 and Bcl-2. It demonstrated that the MTI-31 mediated activation ERK pathway is associated with the induction of autophagy, and autophagy can attenuate the cytotoxicity of MTI-31 on RCC cells. In summary, inhibition of ERK pathway-mediated autophagy can rectify drug resistance to MTI-31 effectively.

23 Feb 2024·Oncogene

Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer

Article

Author: Deng, Yan ; Pei, Jinpeng ; Zhang, Yu ; Liu, Liang ; Ren, Zhiqiang ; Yu, Ker

AbstractThe recently approved KRASG12C mutation-specific inhibitors sotorasib and adagrasib (KRASG12C-I) represent a promising therapy for KRASG12C-driven non-small cell lung cancer (NSCLC). However, many eligible patients do not benefit due to intrinsic or acquired drug resistance. Tissue factor (TF) is overexpressed in KRAS-mutated (KRASmut) NSCLC and is the target of the FDA-approved ADC Tivdak. Here, we employed HuSC1-39, the parent antibody of a clinical stage TF-ADC (NCT04843709), to investigate the role of TF in KRASmut NSCLC. We found that patients with TF-overexpression had poor survival, elevated P-ERK/P-AKT activity levels and low immune effector cell infiltration in the tumor. In a panel of KRASG12C cell lines, KRASG12C-I response correlated with suppression of TF mRNA, which was not observed in resistant cells. In the drug resistant cells, TF-overexpression relied on an mTORC2-mediated and proteasome-dependent pathway. Combination treatment of HuSC1-39 or mTORC1/2 inhibitor MTI-31 with KRASG12C-I each produced synergistic antitumor efficacy in cell culture and in an orthotopic lung tumor model. TF-depletion in the resistant cells diminished epithelial mesenchymal transition, reduced tumor growth and greatly sensitized KRASG12C-I response. Moreover, employing immunohistochemistry and coculture studies, we demonstrated that HuSC1-39 or MTI-31 reset the tumor microenvironment and restore KRASG12C-I sensitivity by reshaping an M1-like macrophage profile with greatly enhanced phagocytic capacity toward tumor cell killing. Thus, we have identified the TF/mTORC2 axis as a critical new mechanism for triggering immunosuppression and KRASG12C-I resistance. We propose that targeting this axis with HuSC1-39 or MTI-31 will improve KRASG12C-I response in KRAS-driven NSCLC.

100 Deals associated with SCC-31

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	CN	Shanghai Institute of Materia Medica Chinese Academy of Sci	12 Jun 2017
Advanced Malignant Solid Neoplasm	Phase 1	CN	Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.	12 Jun 2017
Advanced Malignant Solid Neoplasm	Phase 1	CN	Fudan University	12 Jun 2017
HER2-negative breast cancer	Phase 1	CN	Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.	12 Jun 2017
HER2-negative breast cancer	Phase 1	CN	Shanghai Institute of Materia Medica Chinese Academy of Sci	12 Jun 2017
HER2-negative breast cancer	Phase 1	CN	Fudan University	12 Jun 2017
Metastatic breast cancer	Phase 1	CN	Fudan University	12 Jun 2017
Metastatic breast cancer	Phase 1	CN	Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.	12 Jun 2017
Metastatic breast cancer	Phase 1	CN	Shanghai Institute of Materia Medica Chinese Academy of Sci	12 Jun 2017
Advanced breast cancer	Discovery	CN	Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.	12 Jun 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03125746 (Pubmed \| BMC Cancer)	Phase 1	Advanced Malignant Solid Neoplasm	-	LXI-15029 10mg BID	jmbxpucmnj(ydesjjvgyc) = 20.8% ukqvsppfcx (zikpbalxlg ) View more	-	06 Dec 2023
				LXI-15029 20mg BID