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Recently, the Canadian biotechnology company Cyclica, an investment enterprise of the China Canada Angel Alliance (CCAA for short) managed by Zhongguancun Dahe Capital, cooperated with the Structural Genomics Consortium (SGC for short) to carry out a research and development project in support of the Target 2035 plan. In the process of promoting the cooperation project, it successfully found the first new compound that effectively acts on DCAF1 protein, The crystal structure of the complex of DCAF1 protein and the compound was successfully resolved. The success of this cooperation shows the unique advantages of Cyclica in drug research and development on low data and non data targets.

Target 2035 Program is a global cooperation program led by the Structural Genomics Consortium (SGC) to support scientific development. It aims to determine pharmacological modulators for each protein in the human proteome by 2035.

As a part of the Target 2035 plan, Cyclica and SGC carried out research on three WDR proteins, DCAF1, COP1 and WDR41, and searched for chemical molecules that interact with WDR protein by using Cyclica’s proprietary in-depth learning platform to screen the commercial chemical molecule database.

Combined with a series of biophysical experiments and analysis of SGC, Cyclica successfully found compounds that bind DCAF1 protein, and these compounds were further verified in a series of subsequent experiments. Then, SGC successfully resolved the crystal structure of the complex of DCAF1 protein and the chemical molecule. At present, this crystal structure, as the first composite structure combining DCAF1 protein and its interacting chemical molecules, has been stored in the PDB protein structure database (PDB code: 7SSE).

Dr. Vijay Shahani, Director of the Applied Science Department of Cyclica, said that,   “At Cyclica, we believe that while promoting our own internal drug R&D product pipeline, we should also make contributions to open science and build a better future together. The chemical probe research and development project for DCAF1 protein, which we carried out in cooperation with SGC, has made remarkable achievements, and we have successfully obtained the first crystal structure that combines DCAF1 protein with chemical probe. With this key discovery, we will continue to promote these transformations To further evaluate the therapeutic potential of DCAF1 binding molecules. It’s a pleasure to work with SGC’s world-class excellent team. We are looking forward to the next cooperation opportunity and working together to achieve greater breakthroughs.

DCAF1 protein not only participates in ubiquitination in human body, but also participates in the process of proteasome degrading many proteins related to human diseases. The newly discovered crystal structure of DCAF1 complex will contribute to the discovery of new interacting compounds, thus further promoting the study of biological characteristics of DCAF1. In addition, DCAF1 ligand may be a useful component of PROTAC (proteolysis targeting chimera) molecules that can induce protein degradation. PROTACs and molecular binders represent a promising new therapeutic approach for target proteins that are not suitable for traditional drugs. Because it is possible to expand the scope of application of PROTACs by using DCAF1, so as to further expand its therapeutic application in the future.

Dr. Cheryl Arrowsmith, the chief scientist of the Toronto Laboratory of the Structural Genomics Alliance, commented on this innovative cooperation and how these influential experimental results were obtained in this cooperation, “In the process of this cooperation, we soon found a promising compound (hit) for the challenging and unprecedented goal (DCAF1). This was achieved by testing about 100 compounds predicted by Cyclica’s deep learning platform through experiments, while” traditional ” The method involves testing thousands of molecules through experiments. The cooperation with Cyclica makes us more confident in the research and development of computer technology, and the research and development of computing drugs will play a key role in the Target2035 plan.