FLT3 Inhibitors Development Services
FTL3 inhibitors are effective targeted small molecular drugs for the treatment of acute myeloid leukemia (AML). They inhibit FLT3-mediated signaling pathways. Alfa Cytology specializes in the preclinical discovery of FLT3 inhibitors and promotes the development of new treatments for leukemia. We provide services for you to develop new or select the most effective FTL3 inhibitors and evaluate candidate compounds' inhibitory effect, toxicity, and pharmacokinetic properties on FLT3 mutant leukemia. We provide customized services to design specific experimental methods according to your research purpose, drug characteristics, and interests.
Introduction to FLT3
FMS-like tyrosine kinase 3 (FLT3) is a transmembrane tyrosine kinase receptor belonging to the class III receptor tyrosine kinase (RTK) family. It is normally expressed in hematopoietic cells and activated by FTL3 ligands. It is subsequently cascaded by downstream cell signals to regulate normal hematopoietic stem cell proliferation, differentiation, and survival. The mutation of the FTL3 gene leads to uncontrolled cell proliferation, survival, and anti-apoptosis. FLT3 mutant gene is often found in AML patients, accounting for 30%. Recently, many FLT3 inhibitors have been developed and have shown positive preclinical and clinical effects on AML.
Fig. 1. Chemical structures of reported FLT3 kinase inhibitors. (Dokla, E.M.E. et al., 2022)
Given the prevalence and poor prognosis of FLT3 mutations in acute myelocytic leukemia, targeting FLT3 signaling with small molecule inhibitors is a therapeutic strategy worthy of investigation.
Design Strategy of FLT3 Inhibitors
The molecular design and drug simulation are carried out using a new generation of molecular modeling and simulation environment tools. According to the compound's action target, the drug's molecular structure was designed. Through the synthesis and testing of structural analogs and derivatives of candidate compounds, the relationship between structure and activity was determined, and the potency and selectivity of drugs were optimized.
Screening Candidate FLT3 Inhibitors
Using our high-throughput screening platform, we screen out effective candidates for FLT3. Each compound in the compound library reacts to the target separately. This is usually achieved through automated equipment and high-throughput screening platforms. The compounds in the compound library are added to the screening experiment one by one, and then the activity of the compound is evaluated by measuring the activity of the target or the interaction with the target.
Deciphering the mechanism of FLT3 Inhibitors
| Experiment | Service Contents |
|---|---|
| Cytostatic assay | The concentration of drugs or inhibitors needed to inhibit 50% of biological processes or reactions was determined by Half-maximal inhibitory concentration (IC50) to evaluate the effective inhibitory activity of drugs against FLT3-ITD mutants. |
| Apoptosis | Apoptosis detection techniques, such as flow cytometry, were used to evaluate whether candidate compounds induce apoptosis in FLT3 mutant leukemic cells. |
| Identification of signaling pathways | The signaling pathways of the effects of candidate compounds on leukemic cells are usually evaluated by the content of key proteins ERK1/2 and mTOR on the signaling pathway and the phosphorylation of downstream signaling factors. |
| Evaluation of drug efficacy | The inhibitory effect of candidate compounds on the growth and spread of leukemic cells is usually evaluated by measuring tumor volume, number of leukemic cells, or survival rate. |
| Drug toxicity analysis | The toxicity of candidate compounds to normal cells and tissues was evaluated using mouse or other leukemia animal models. |
Advantages of Our Services
- Study of ligand-receptor interactions with accuracy and precision
- Optimize and improve candidate FLT3 inhibitors
- Have a large library of compounds
- Excellent ability to analyze the structure and function of compounds
- Advanced high-throughput screening platform
- Have leukemia models for FLT3 research.
- Provide full-stop service from drug discovery to preclinical service
Alfa Cytology provides development services for FLT3 inhibitors, covering drug design, screening, and efficacy research to find ideal drug candidates for you and accelerate preclinical research on your leukemia drugs. These results can guide further drug optimization, reasonable dose selection, and preclinical drug safety evaluation. Contact us if you are interested in our services or would like to know more.
Reference
- Dokla, E.M.E.; et al. Discovery of a benzimidazole-based dual FLT3/TrKA inhibitor targeting acute myeloid leukemia. Bioorganic & Medicinal Chemistry. 2022, 56: 116596.