BI 847325 / Boehringer Ingelheim - LARVOL DELTA

Identifying Novel Epigenetic Therapies for T-Cell Lymphomas By High Throughput Drug Screen (ASH 2024) - "Introduction : Epigenetic alterations are known to contribute to development of T-cell lymphomas (TCL), and numerous epigenetic modifiers have shown safety and clinical efficacy in TCL leading to FDA approval of three histone deacetylase inhibiters (vorinostat, romidepsin, and belinostat)...At the conclusion of this screen, we tested cytotoxicity of our most encouraging compound in combination with other top performing compounds.Results : We identified BI-847325, bortezomib, camptothecin, CUDC-907, and WAY-118959-A as the most encouraging cytotoxic compounds that are not currently being used clinically. We compared the top 5 compounds to 4 standard of care (SOC) cytotoxic drugs (belinostat, gemcitabine, romidepsin, and vincristine) that are used clinically...We tested cytotoxicity of camptothecin in combination with 5 compounds (belinostat, bortezomib, BI-847325, romidepsin, and vincristine) that also demonstrated cytotoxicity in the malignant T-cells with relative..."

Cutaneous T-cell Lymphoma • Gene Therapies • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • ANXA5

Targeted therapy with a dual MEK and Aurora kinases inhibitor induces apoptosis and cell cycle arrest in an acute myeloid leukemia stem cell line (EACR 2024) - "Our findings suggest that multi-targeting MEK and Aurora kinases by BI.847325 might be a promising option to overcome AML. However, further complementary assays and in vivo models are needed to shed light on the detailed regulatory mechanisms of this compound."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CDKN1A • MCL1 • MYC

High in vitro and in vivo activity of BI-847325, a dual MEK/Aurora kinase inhibitor, in human solid and hematologic cancer models. (PubMed, Cancer Res Commun) - "BI-847325 showed a broader range of activity than the MEK inhibitor GDC-0623. In conclusion, dual MEK/Aurora kinase inhibition shows remarkable potential for treating multiple types of hematological and solid tumors. The combination with capecitabine was synergistic in colorectal, gastric, and mammary cancer."

Journal • Preclinical • Acute Lymphocytic Leukemia • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • MAP2K1 • NRAS

High in vitro and in vivo activity of BI-847325, a dual MEK/Aurora kinase inhibitor, in human solid and hematologic cancer models (Cancer Res Commun) - "The high antiproliferative activity of BI-847325 was validated in vivo using subcutaneous xenograft models. After oral administration of 80 and 40 mg/kg once weekly for 3 or 4 weeks, BI-847325 was highly active in 4/5 colorectal, 2/2 gastric, 2/2 mammary, and 1/1 pancreatic cancer models (T/C < 25%), and tumor regressions were observed in 5/11 cancer models."

Preclinical • Breast Cancer • Colorectal Cancer • Gastric Cancer • Hematological Malignancies • Pancreatic Cancer

BI-847325, a selective dual MEK and Aurora kinases inhibitor, reduces aggressive behavior of anaplastic thyroid carcinoma on an in vitro three-dimensional culture. (PubMed, Cancer Cell Int) - "The results of the present study suggest that BI-857,325 might be an effective multi-targeted anticancer drug for ATC treatment."

Journal • Preclinical • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • ABCB1 • ANXA5 • AURKA • AURKB

GANT61/BI-847325 combination: a new hope in lung cancer treatment. (PubMed, Med Oncol) - "To the best of our knowledge, the antitumor effects of BI-847325/GANT61 combination have not been tested before. Further in-vitro and in-vivo studies are warranted to support the findings."

IO biomarker • Journal • Brain Cancer • Glioma • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BAX • CASP3 • CCND1 • GLI1 • MCL1 • mTOR

Alginate-based 3D cell culture technique to evaluate the half-maximal inhibitory concentration: an in vitro model of anticancer drug study for anaplastic thyroid carcinoma. (PubMed, Thyroid Res) - "The findings of this study are beneficial for developing in vitro ATC 3D models to analyze the efficacy of different chemotherapy drugs and formulations."

Journal • Preclinical • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

Monotherapy dose finding with BI 847325 in solid tumours (clinicaltrials.gov) - P1, N=140; Sponsor: Boehringer Ingelheim; Recruiting -> Active, not recruiting.

Enrollment closed • Oncology

BI847325 (BI5) reverses acquired BRAF inhibitor resistance through dual inhibition of MEK and CDK9 (SMR 2013) - “Treatment with BI5 led to a time-dependent decrease in CDK9 expression and the Ser2/5 phosphorylation of RNA polymerase II. The role of CDK9 in regulating Mcl-1 expression was confirmed through siRNA knockdown of CDK9.”

Preclinical • Melanoma • Oncology

Transcript-level regulation of MALAT1-mediated cell cycle and apoptosis genes using dual MEK/Aurora kinase inhibitor "BI-847325" on anaplastic thyroid carcinoma. (PubMed, Daru) - "MALAT1 gene expression following BI-847325 treatment was significantly downregulated in C643 and SW1736 cell lines. Reversely, miR-363-3p expression was significantly upregulated by BI-847325 in both ATC cell lines. Mcl1 expression was significantly downregulated after treatment in C643 cell lines. Moreover, the expression of this gene was not significantly reduced following BI-847325 treatment in SW1736 cell line. Additionally, cyclin D1 expression was significantly downregulated after treatment in both ATC cell lines. Altogether, the result of this study was the first report of MALAT1's molecular function in ATC and suggested that BI-847325 which inhibits both MEK and Aurora kinase family could be effective against ATC by regulating the genes involved in cell cycle and apoptosis including MALAT1and its downstream genes. Graphical abstract Schematic representation of the biological role of MALAT1 in cyclin D1, miR-363-3p and Mcl1 gene regulations. Stimulation of..."

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