About Us

NCMNtech is a biotechnology company founded to provide a complete solution for membrane protein research and the design of next-generation drugs targeting membrane proteins.

 

Membrane proteins are major but challenging drug targets

Membrane proteins serve numerous vital roles, encompassing the movement of nutrients, conversion of energy, regulation of heart rhythm, and facilitation of complex cognitive processes in the brain. The membrane proteins are involved in a variety of human diseases, and their accessibility to both small and large-molecule medications is due to their location at the cell membrane surface. Membrane proteins are highly significant in the context of most diseases and are easily accessible to both small molecule and biological therapies. As a result, they are the primary focus of contemporary drug development. Throughout history, the development of membrane protein-targeting medications has been impeded by the challenges of recombinantly producing membrane proteins in sufficient quantities and stabilizing them in therapeutically relevant conformations. Numerous obstacles to membrane protein production are linked to their hydrophobicity, resulting from the presence of numerous transmembrane domains. This can result in aggregation and instability during the expression and purification processes. 

 

Many current drugs targeting membrane proteins have significant concerns

There are substantial concerns regarding numerous current medications that target membrane proteins, including opioids. Their lack of specificity is a concern, as it is a result of the analogous ligand-binding pockets in related membrane proteins. Another area of concern is their involvement in numerous signaling pathways, including ion channels and transporters, which can have a substantial effect on the overall equilibrium conditions of the cell. Unwanted consequences may result from these variables. These manifestations can manifest as unfavorable safety and side-effect profiles, underscoring the importance of developing the next generation of membrane protein-targeting pharmaceutics. The ability to generate an adequate quantity of full-length MPs in stable, functionally distinct conformations, preferably in conjunction with other proteins or lipid cofactors that form native-like complexes, will be a determining factor in the development of the next generation of MP-targeting therapeutics.

 

NCMNtech provides a comprehensive solution for the design of next-generation drugs targeting membrane proteins

NCMNtech was named after a novel biotechnology, the Native Cell Membrane Nanoparticles System (NCMN system), developed by Dr. Youzhong Guo and his colleagues in the Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University with federal grant support from NIH/NIGMS (R01GM132329). Distinct from the traditional detergent-based approaches for membrane protein extraction and purification and downstream applications in drug discovery, the NCMN system is a genuine detergent-free system. The NCMN system was developed to extract and purify membrane proteins and their associated lipid and protein partners in their native cell membrane environment. Membrane proteins fabricated in the form of NCMN particles retain their natural structure and function and, therefore, perfectly fit the requirement for the next-generation drugs targeting membrane proteins. The NCMN system is composed of three components: 1) NCMN polymer library; 2) Protocols for fabrication of NCMN particles of membrane proteins in their native functional and structural states; 3) Protocols for characterization and application of NCMN particles of membrane proteins, including but not limited to high-resolution structure determination, mass spectrometric analysis of and identity of native lipid species, various functional assay, ligand-protein binding assay, structure-based and high-through screen-based small molecule drug and antibody therapeutics development. The NCMN system has been successfully applied for high-resolution cryo-EM structural determinations for both prokaryotic and eukaryotic membrane proteins, including human membrane proteins and their associated native cell membrane lipids. The NCMN system has also been successfully used for detergent-free proteoliposome reconstitutions, functional assays of membrane protein channels, enzymes, and membrane protein-ligand interactions, as well as the discovery and identification of specific membrane protein-lipid interactions.

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A brief history of NCMNtech LLC.

When Dr. Youzhong Guo was a postdoc at Columbia University in the 2010s, he realized that traditional small molecule detergents often lead to inactivation and denaturation of membrane proteins, and he dreamed of a genuinely detergent-free system for membrane protein structural biology. In 2016, he moved to Virginia Commonwealth University as an Assistant Professor of Medicinal Chemistry, intrigued by the isolation of membrane proteins with styrene-maleic acid copolymers. He developed the prototype NCMN system and demonstrated its capability of high-resolution structure determination of membrane proteins with natively associated cell membrane lipids. After that, his research group focused on developing the NCMN system as a platform for membrane protein research and related drug discovery.

In 2023, Dr. Youzhong Guo and Dr. Weihua Qiu founded NCMNtech LLC as a biotechnology business that provides a comprehensive solution for membrane protein research and the design of next-generation drugs targeting membrane proteins.