Hit-to-Lead Services

Developing innovative therapies for leukemia requires the establishment of supporting evidence for the efficacy of new molecules. To achieve this, pharmaceutical companies and research institutions must adhere to key preclinical stages of the drug discovery process, including lead compound optimization. Alfa Cytology, a leading CRO in early-stage drug discovery, can assist you in achieving success in hit-to-lead.

Introduction to Hit-to-Lead

In recent decades, targeted inhibitors have emerged to effectively inhibit leukemia cell proliferation. During early-stage drug development, potential lead compounds are identified from high-throughput screening and undergo limited optimization. Subsequently, selective cytotoxicity testing against leukemia cells in vitro is conducted to develop effective therapeutic drugs.

Fig. 1. Identification of hit compound from chemical library and further optimizations to discover lead compound. (Yao, Y. et al., 2022)

Our Services

we specialize in providing comprehensive solutions to accelerate the identification and optimization of potential lead compounds for leukemia treatment. Our services are designed to streamline the drug discovery process and maximize the chances of success in developing effective therapies. Our hit-to-lead services for leukemia encompass the following key components:

Design and Synthesis of Hybrid Compounds

By employing computer-aided drug design (CADD) and medicinal chemistry, we investigate the modeling, binding affinity, and structural modifications of potential drug-target interactions. Based on the target characteristics, we design pharmacophores and synthesize compounds and related analogs. Our services assist you in optimizing hit compounds to enhance potency, selectivity, or other drug-like properties.

Physicochemical and Metabolic Evaluation

To evaluate the drug-like properties of the compounds of interest, we measured the physicochemical parameters and in vitro metabolic stability of multiple novel lead compounds. We conducted drug-likeness assessments on all potential analogs and compared them to previous hits and structurally similar compounds, aiming to reduce time and cost expenditures during the hit-to-lead process.

Hit-to-Lead Process

High-throughput screening is initial used to identify hits, these hits can include molecules with known biological activity, or novel compounds that exhibit potential.

Hit Identification

Following hit confirmation, several compound clusters will be chosen according to their characteristics in the previously defined tests.

Hit expansion

Hit confirmation

After identification hits go through further testing which aims to confirm their activity, and assess their potential for optimization.

Lead optimization

This phase is to synthesize lead compounds, new analogs with improved potency, reduced off-target activities, and reasonable in vivo pharmacokinetics.

Alfa Cytology's hit-to-lead Services offer a tailored approach to accelerate the identification and optimization of lead compounds, ultimately advancing the development of novel therapies for leukemia treatment. Contact us to discuss your specific needs, and let us be your trusted partner in the quest for effective leukemia treatments.

Reference

Yao, Y.; et al. Angiogenesis and anti-leukaemia activity of novel indole derivatives as potent colchicine binding site inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2022, 37(1): 652-665.

For research use only. Not intended for any clinical use.