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Mutant isocitrate dehydrogenase (IDH) enzymes have functional activity, resulting in excessive accumulation of carcinogenic metabolites, thus participating in the development of cancer. IDH1 mutant protein has become an attractive target for leukemia drug development. Alfa Cytology provides a full range of drug development services for your IDH inhibitor development, dedicated to innovating or optimizing IDH inhibitors. We have advanced technology and rich experience to provide new insights into the development of your IDH inhibitors, to help you complete the IDH inhibitor discovery project, and to develop new metabolic therapies targeting leukemia.
IDH enzymes play a crucial role in cell metabolism by catalyzing the oxidative decarboxylation of isocitrate to α-ketoglutaric acid (α-KG). The IDH family consists of three isozymes: IDH1, IDH2, and IDH3. However, when IDH undergoes mutations, α-KG is converted into (D)-2-hydroxyglutaric acid (2-HG), leading to the accumulation of 2-HG and disrupting normal cell differentiation processes. Mutations in IDH1 and IDH2 are observed in approximately 30% of acute myeloid leukemia (AML) patients. These mutations cause abnormal epigenetic regulation in AML cells, impairing their ability to differentiate. Notably, FDA-approved IDH2 inhibitors have been developed to address relapsed/refractory AML.
Fig. 1. Mutant IDH1 and IDH2 (mIDH1 and mIDH2). (McMurry, H. et al., 2021)
IDH inhibitors are a promising agent for the treatment of patients with IDH-mutated R/R AML. Alfa Cytology provides comprehensive IDH inhibitor development services.
Through our genomics technology and bioinformatics tools and database, we analyze the data, provide mutation sites for IDH enzymes, and develop new action sites as potential therapeutic targets.
We have a library of compounds including natural products, synthetic compounds, and heavy spot libraries. Through our large number of chemical libraries, we can select or design several diverse compounds that can be used to screen for possible inhibitors of IDH.
Computational methods, including molecular modeling and virtual screening, were used to predict and screen compounds with potential inhibitory activity. A screening experiment for IDH was designed, and HTS was used to identify small molecules or compounds that could inhibit mutant IDH enzymes.
A series of compounds with similar structures were synthesized and evaluated, and the relationship between their structure and inhibitory activity was studied to optimize the activity of the compounds. Modify the compounds, optimize the structure and function of the compounds, and give full play to the best efficacy of the candidate compounds.
We provide research services on the pharmacokinetic properties of compounds, including absorption, distribution, metabolism, and excretion (ADME), and evaluate the properties of candidate compounds. According to the actual effect of the candidate compounds, pharmacochemical techniques are used to improve the potency, selectivity, and pharmacokinetic characteristics of the identified hits.
We have a variety of cell and animal models for IDH mutation research to evaluate the efficacy and selectivity of IDH inhibitor candidates.
Alfa Cytology provides screening, optimization, and verification services for IDH inhibitors. We focus on the development of leukemia-targeted drugs to help reduce the time for drug development and reduce the risk of downstream testing. If you are interested in the drug development of leukemia, we will be your most suitable partner. Please contact us if you are interested in our services or would like to know more.
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