MTI-31 / Shanghai Inst. of Materia Medica, Fudan University, Luoxin Pharma - LARVOL DELTA

From EGFR mutations to STAT30-driven resistance in NSCLC: Biomarkers and multi-modal treatment approach. (PubMed, Pathol Res Pract) - "Preclinical studies of Polyphyllin I and MTI31 illustrate the reversal of epithelial-mesenchymal transition and restoration of sensitivity to EGFR-targeted agents. In contrast to previous reviews, we offer a comparative analysis of monotherapy versus combination regimens, highlight remaining knowledge gaps, and propose an integrated framework for co-targeting EGFR, STAT3, and immune checkpoints. We aim to elucidate EGFR-STAT3 signaling crosstalk in NSCLC and distinguish preclinical findings from clinical data to enhance the translational relevance of combination therapies."

Biomarker • IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • STAT3 • ZEB1

Analysis of Combinatorial Cohesin Subunit Gene Deletions in Budding Yeast. (PubMed, Genetics) - "These results further suggest that the addition of other suppressor mutations (such as ELG1 and RAD61) may support the viability of cells deleted of all auxiliary subunits - including IRR1/SCC3 (herein SCC3). Here, we test these predictions and report on novel gene deletion combinations required for cell cycle progression and cell viability."

Journal

Large-scale Deep Learning Identifies the Antiviral Potential of PKI-179 and MTI-31 Against Coronaviruses. (PubMed, Antiviral Res) - "Notably, both compounds outperform the well-known mTOR inhibitor rapamycin. 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."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Intronic miR-6741-3p targets the oncogene SRSF3: Implications for oral squamous cell carcinoma pathogenesis. (PubMed, PLoS One) - "We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulating SRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • SRSF3

Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer. (PubMed, Oncogene) - P1/2 | "The recently approved KRAS mutation-specific inhibitors sotorasib and adagrasib (KRAS-I) represent a promising therapy for KRAS-driven non-small cell lung cancer (NSCLC)...Tissue factor (TF) is overexpressed in KRAS-mutated (KRASmut) NSCLC and is the target of the FDA-approved ADC Tivdak...Thus, we have identified the TF/mTORC2 axis as a critical new mechanism for triggering immunosuppression and KRAS-I resistance. We propose that targeting this axis with HuSC1-39 or MTI-31 will improve KRAS-I response in KRAS-driven NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Phase I dose escalation study and pilot efficacy analysis of LXI-15029, a novel mTOR dual inhibitor, in Chinese subjects with advanced malignant solid tumors. (PubMed, BMC Cancer) - P1 | "LXI-15029 demonstrated reasonable safety and tolerability profiles and encouraging preliminary antitumor activity in Chinese patients with advanced malignant solid tumors, which warranted further validation in phase II trials."

Journal • Metastases • P1 data • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Leukopenia • Oncology • Solid Tumor

Phase I dose escalation study and pilot efficacy analysis of LXI-15029, a novel mTOR dual inhibitor, in Chinese subjects with advanced malignant solid tumors (BMC Cancer) - P1 | N=72 | NCT03125746 | Sponsor: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. | "Between June 2017 and July 2021, a total of 24 patients were enrolled. LXI-15029 was well tolerated at all doses. Only one dose-limiting toxicity (grade 3 increased alanine aminotransferase) occurred in the 150 mg group, and the maximum tolerated dose was 110 mg BID....LXI-15029 was absorbed rapidly after oral administration. The increases in the peak concentration and the area under the curve were greater than dose proportionality over the dose range. Eight patients had stable disease. The disease control rate was 40.0% (8/20; 95% CI 21.7–60.6). In evaluable patients, the median progression-free survival was 29 days (range 29–141)."

P1 data • Solid Tumor

Combining MTI-31 with RAD001 inhibits tumor growth and invasion of kidney cancer by activating autophagy. (PubMed, J Appl Genet) - "The outcomes from the mechanistic studies infer that the combination of MTI-31 and RAD001 increases the LC3 levels, which in turn translates into the activation of autophagy. To conclude, the combination of MTI-31 and RAD001 improves the anti-cancerous impact produced by RAD001 in vivo through the promotion of autophagy."

Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Calnuc-derived nesfatin-1-like peptide is an activator of tumor cell proliferation and migration. (PubMed, FEBS Lett) - "NLP treatment to carcinoma cell lines (SCC131 cells) promotes the expression of regulators of cell cycle, proliferation and clonogenicity by the AKT/mTOR pathway. NLP is causative of augmented migration and epithelial-mesenchymal transition (EMT), illustrating its metastatic propensity and establishing its tumor promotion ability."

Journal • Tumor cell • Oncology • NUCB1 • PCSK1

Protective Autophagy Attenuates the Cytotoxicity of MTI-31 in Renal Cancer Cells by Activating the ERK Pathway. (PubMed, Appl Biochem Biotechnol) - "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...The use of the ERK inhibitor AZD6244 to block the ERK pathway could effectively promote cell apoptosis induced by MTI-31...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."

IO biomarker • Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BCL2 • BECN1

Betanin alleviates inflammation and ameliorates apoptosis on human oral squamous cancer cells SCC131 and SCC4 through the NF-κB/PI3K/Akt signaling pathway. (PubMed, J Biochem Mol Toxicol) - "The above-mentioned results exposed that betanin can inhibit cell viability, MMP, inflammation and enhanced apoptosis via the expression of NF-κB/PI3K/Akt pathways. Thus, our current findings provided an innovative vision into the protective effect against OSCC."

Journal • Head and Neck Cancer • Immunology • Inflammation • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study of LXI-15029 in Patients With Advanced Malignant Solid Tumors (clinicaltrials.gov) - P1; N=72; Recruiting; Sponsor: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.; Trial completion date: Feb 2020 ➔ Oct 2021; Trial primary completion date: Feb 2020 ➔ Oct 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Non-immunogenic, low-toxicity and effective glioma targeting MTI-31 liposomes. (PubMed, J Control Release) - "While showing both systemic and immunological safety, VAP-liposome/MTI-31 treatment resulted in a significant improvement in the median survival time (24.5 days for saline, 26 days for free MTI-31, 25 days for liposomes/MTI-31 and 36 days for VAP-liposome/MTI-31). The results highlight MTI-31 as an effective anti-glioma agent when encapsulated in non-immunogenic glioma-targeted liposomes, which may contribute to the development of better anti-glioma treatment."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor

mTOR Promotes Tissue Factor Expression and Activity in EGFR-Mutant Cancer. (PubMed, Front Oncol) - "Application of mTORC1/2 inhibitors (AZD8055, WYE-125132, MTI-31, and rapamycin) or genetic mTORC-depletion all reduced TF expression, which appeared to be differentially mediated depending on cellular context. Thus, our results have identified TF as a functional biomarker of mTOR. Downregulation of mTOR-TF axis activity likely contributes to the therapeutic mechanism of mTORC1/2- and TF-targeted agents in EGFR-mut advanced NSCLC and GBM."

Journal • Cardiovascular • Fibrosis • Glioblastoma • Hematological Disorders • Hemophilia • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Thrombosis • CD31 • EGFR • mTOR