HDAC6 and BCL-2 Inhibitor Combination for Resistant Cancer
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Solution Overview
Problem
Current cancer treatments, particularly for resistant and refractory cancers, lack effective and safe therapeutic options, necessitating the development of alternative methods that combine histone deacetylase 6 (HDAC6) inhibitors with B-cell lymphoma 2 (BCL-2) inhibitors to target cancer cells effectively.
Innovation Solution
A pharmaceutical combination comprising a histone deacetylase 6 (HDAC6) inhibitor and a BCL-2 inhibitor, specifically formulated to target and inhibit HDAC6 and BCL-2 proteins, which are administered alone or in combination to treat various types of cancers, including hematologic cancers that are resistant to prior therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pan-HDAC inhibition is used to treat cancer, then cancer cell growth arrest is achieved, but significant adverse effects occur
Solution Approach 1:
The patent segments the HDAC inhibition function by using selective HDAC6 inhibitors instead of pan-HDAC inhibitors. This targets a specific HDAC isoform (HDAC6) while sparing others, thereby maintaining anti-cancer efficacy through HDAC6-specific mechanisms while reducing off-target adverse effects associated with broad HDAC inhibition.
Solution Approach 2:
The patent applies local quality by designing inhibitors with specific molecular characteristics that confer selectivity for HDAC6 over other HDAC isoforms. The chemical structures (Formulas I and II) incorporate specific substituents and functional groups that enable preferential binding to HDAC6, achieving localized inhibition at the target enzyme level.
2Reliability
If combination therapy with HDAC6 inhibitor and BCL-2 inhibitor is used, then synergistic anti-cancer effect is achieved, but treatment complexity increases
Solution Approach 1:
The patent merges two distinct therapeutic mechanisms by combining HDAC6 inhibition with BCL-2 inhibition in a single combination therapy regimen. This dual-target approach synergistically enhances anti-cancer efficacy by simultaneously disrupting protein homeostasis through HDAC6 inhibition and preventing apoptosis through BCL-2 inhibition, particularly in resistant cancer types.
Data Source
AI summary
The present disclosure relates to a pharmaceutical combination comprising (a) a histone deacetylase 6 inhibitor and (b) a BCL-2 inhibitor, including combined preparations and pharmaceutical compositions thereof; uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.