Meis1 was first discovered in BXH-2 mouse leukemia model. Studies in the last decade have shown that Meis1 has crucial roles in cellular metabolism, redox state, and tumorigenesis. Meis1 maintains cytoplasmic glycolysis through transactivation of hypoxic tumor markers, namely Hif-1α and Hif-2α. MEIS proteins includes MEIS1, MEIS2 and MEIS3 proteins. MEIS proteins have been shown to interact with PBX and HOXA9 proteins. MEIS proteins are known as an oncogene and overexpressed in various cancers including leukemia. Intriguingly, a high level of Meis1 expression was found to be associated with resistance to conventional chemotherapies (Reviewed in Current drug targets).
We have used in silico, in vitro and in vivo approaches to identify small-molecule MEIS inhibitors (MEISi). In silico screening of a million druggable small molecules allowed us to identify putative MEISi. MEIS dependent luciferase reporter assays were used to validate in vitro efficacy of MEIS inhibitors. Small molecules named MEISi-1 and MEISi-2 demonstrated a significant inhibition of MEIS-luciferase activity. In addition, inhibition of MEIS protein resulted in downregulation of MEIS target gene expression in human and animal studies in ex vivo and in vivo, respectively.
Meinox rolls out four product pipelines, aiming at large, global, and unmet needs.
We have developed first-in-class, selective, drug-like small molecule MEIS inhibitors. Studies demonstrated that blocking the MEIS proteins in tumors could:
We are focusing our product pipeline on two distinct indications: Cancer (i.e. prostate, pancreas, leukemia) and obesity / diabetes. While these two indications may seem a world apart, excellent targets have been identified in both areas of disease, opening up the possibility to leverage our technology to its full potential.
Our team includes experts in project management, drug discovery, and cancer biology. We seek to share our expertise and proprietary small molecule platforms that can be deployed in collaboration with strategic partners to develop next generation therapeutics for various cancer and malignancies.
MEIS inhibitor manuscript is out! It is available at Nature.com/Scientific Report & bioRxiov for an early insight! These studies warrant identification of first-in-class MEIS inhibitors as potential pharmaceuticals to be utilized in targeting molecular basis of diseases. Read
ASC / J. Med. Chem
In this work, we performed lead optimization on MEISi-1 by synthesizing 45 novel analogues. Lead Optimization and Structure–Activity Relationship Studies on MEIS1 Inhibitor now published in J. Med. Chem. Read
Current Drug Targets
In this peer-reviewed paper, we discuss role of Meis1, how it transcriptionally regulates the expression of hypoxic tumor markers, namely Hif-1α and Hif-2α, their involvement in the cytoplasmic glycolysis and scavenging of reactive oxygen species. Read
Cell & Bioscience
This peer-reviewed study showed that HSCs poses hypoxic metabolism, which depends on MEIS1 activity. Here we also utilized MEIS-Luc reporter in the analysis of MEIS1 cofactors. Read
This study demonstrate that loss of Meis1 results in down-regulation of both Hif-1 and Hif-2. This resulted in a shift to mitochondrial metabolism, increased reactive oxygen species production, and apoptosis. Read
Cell Stem Cell
This is the first report about MEIS-lusiferase reporter. Here we showed that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1a. Read
This is the first report showing that targeting MEIS1 in vitro and in vivo by means of LoxP technology allows improved cardiomyocyte proliferation. Read
The MEINOX has developed its in-company IP strategy to ensure the protection of her proprietary MEISi-EX™ technology. Other patent applications for the MEISi-EX™ technology are pending.
In addition to these applications, Meinox will continue to investigate her Freedom to Operate and file patents protecting new developments, indications and products.
2016/16602, "A COMBINATION INHIBITING MEIS PROTEINS". PCT 25418.57, PCT/TR2017/050445 "A COMBINATION INHIBITING MEIS PROTEINS". WO2018203855A2 /EP3541410A2 / US20190343886A1 / AU2017412642A1 / CN109963580A / KR20190084953A / JP2020500185A
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