BCR-ABL Inhibitors Development Services

As a preclinical contract research organization (CRO) committed to advancing oncology research, Alfa Cytology offers a comprehensive service dedicated to the development of BCR-ABL inhibitors specifically tailored for the treatment of chronic myeloid leukemia (CML). We offer a comprehensive suite of services specifically designed to facilitate the development of BCR-ABL inhibitors in CML.

Functional Roles of BCR-ABL Inhibitors

The formation of the BCR-ABL fusion protein occurs due to a chromosomal translocation, involving the fusion of a segment from the breakpoint cluster region (BCR) gene on chromosome 22 with a segment from the abelson (ABL) gene on chromosome 9. BCR-ABL inhibitors function by selectively binding to and inhibiting the activity of the BCR-ABL fusion protein. This binding action effectively disrupts the downstream signaling pathways associated with the fusion protein, leading to the impairment of leukemic cell growth and survival. Targeting the fundamental molecular driver of the disease, BCR-ABL inhibitors have brought about a transformative impact on the treatment of chronic myeloid leukemia (CML) and certain forms of acute lymphoblastic leukemia (ALL).

Fig. 1. BCR-ABL1 Tyrosine Kinase Inhibitors and Resistance Mechanisms. (Braun, T.P. et al., 2020)

BCR-ABL Inhibitor Discovery

• We leverage advanced molecular simulation software in our pursuit of BCR-ABL inhibitors. Our process begins by utilizing the best pharmacophore model to search through extensive drug databases, specifically targeting compounds that align with the desired chemical characteristics. Through meticulous screening, we identify candidate BCR-ABL inhibitors with promising potential.
• To further enhance the inhibitory activity of tyrosine kinases, improve oral bioavailability, and enhance water solubility, we offer comprehensive chemical optimization of the selected drug candidates. Our experienced team applies strategies such as introducing amide groups and spaced benzene rings, which have shown efficacy in augmenting the desired properties of the inhibitors.

Solutions for BCR-ABL Inhibitor Resistance

• Developing Inhibitors that target the T315I mutation in BCR-ABL. In our pursuit of addressing the T315I mutation of BCR-ABL, we have employed a rational drug design approach to develop a novel inhibitor. This inhibitor is specifically designed to relax the conformational and binding requirements while maintaining a high degree of specificity.
• To predict patients' response to the drugs and provide solutions for TKI drug resistance, we utilize DNA microarray technology. The microarray data used in our analysis are sourced from the NCBI gene expression synthesis website. Through individual analysis and meta-analysis, we identify differentially expressed genes from integrated microarray data and pinpoint potential therapeutic targets.

Advantages of Our Services

• Extensive experience in inhibitor development.
• Expert pharmaceutical chemistry team.
• Efficient drug R&D.
• High-standard experimental procedures.
• Customized BCR-ABL inhibitors development services.

Alfa Cytology offers comprehensive services for developing BCR-ABL inhibitors in CML, aiming to accelerate the discovery and development of effective therapies for patients with this challenging disease. Contact us to discuss your specific needs and how our services can support your drug development.