Zinc-Binding PI3K Inhibitor Combination for Resistant Cancer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for particularly effective combinations of drugs for the treatment of specific types of cancer, particularly in addressing cancer cells resistant to therapy.
Innovation Solution
A combination therapy involving a compound of Formula I, which includes a phosphoinositide 3-kinase inhibitor with a zinc binding moiety, and a PD-1 signaling inhibitor, such as pembrolizumab or nivolumab, is administered to treat cancers, with the compounds being administered separately or simultaneously via various routes to achieve synergistic therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If combination therapy with multiple agents is used to treat cancer, then therapeutic effectiveness is improved, but treatment complexity increases
Solution Approach 1:
The patent combines a phosphoinositide 3-kinase inhibitor (Compound 1) with a PD-1 signaling inhibitor in a unified treatment protocol. This merging of two distinct therapeutic agents into a coordinated combination therapy enhances anti-tumor effectiveness by targeting multiple pathways simultaneously while managing the complexity through structured administration guidelines
2Reliability
If combination therapy is used to address resistant cancer cells, then treatment efficacy is improved, but safety risks increase
Solution Approach 1:
The patent employs parameter changes by adjusting the dosing levels and administration timing of both Compound 1 and the PD-1 inhibitor. This allows optimization of the therapeutic window, maintaining high efficacy against resistant cancer cells while managing safety risks through controlled exposure levels
3Productivity
If multiple drugs are administered simultaneously, then therapeutic impact is enhanced, but administration complexity increases
Solution Approach 1:
The patent segments the administration protocol into distinct components with specific timing and routing instructions for Compound 1 and the PD-1 inhibitor. This segmentation allows each drug to be optimized for its own delivery while maintaining coordinated therapeutic impact, reducing administration complexity through structured protocols
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination therapy demonstrates significant antitumor activity in mouse xenograft tumor models, substantial uptake by tumor tissue, and a favorable safety profile, effectively inhibiting PI3K and HDAC, and showing potent antiproliferative activity against various cancer cell lines.
Implementation Method 1
a phosphoinositide 3-kinase inhibitor with a zinc binding moiety
Data Source
AI summary
The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject:(a) a compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and(b) a PD-1 signaling inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and the PD-1 signaling inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a PD-1 signaling inhibitor and a pharmaceutically acceptable carrier or excipient.