CTPS1 and BCL2 Inhibitor Combination for Selective Cancer Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer therapies targeting CTPS inhibitors are non-selective, affecting both CTPS1 and CTPS2 isoforms, leading to toxicity and efficacy issues, while BCL2 inhibitors show promise but may not adequately address the complex cell division pathways in cancer cells.
Innovation Solution
The combination of a CTPS1 inhibitor with a BCL2 inhibitor, where the CTPS1 inhibitor selectively targets CTPS1 over CTPS2, potentially offering a more targeted approach to cancer therapy by disrupting nucleotide synthesis and promoting apoptosis in cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-selective CTPS inhibitors (affecting both CTPS1 and CTPS2) are used, then broad CTPS activity is blocked, but toxicity and efficacy issues occur due to lack of selectivity
Solution Approach 1:
The invention segments the CTPS enzyme into two distinct isoforms (CTPS1 and CTPS2) and develops inhibitors that selectively target CTPS1 while sparing CTPS2. This segmentation allows differential inhibition where CTPS1 (predominant in cancer cells) is blocked to achieve therapeutic effect, while CTPS2 (important in normal cells) remains functional to reduce toxicity.
Solution Approach 2:
The invention applies local quality by creating inhibitors with specific molecular characteristics that confer selectivity for CTPS1 over CTPS2. The compounds possess structural features (such as specific substituents at defined positions in the molecular scaffold) that enable preferential binding to CTPS1, thereby achieving localized therapeutic action in cancer cells while minimizing impact on normal cells.
2Reliability
If BCL2 inhibitors alone are used, then apoptosis is triggered in cancer cells, but the complex cell division pathways are not adequately addressed
Solution Approach 1:
The invention merges two distinct therapeutic mechanisms into a combination therapy: CTPS1 inhibition (blocking nucleotide synthesis and cell division) and BCL2 inhibition (triggering apoptosis). This combination addresses multiple critical pathways in cancer cell survival and proliferation simultaneously, providing synergistic anticancer activity that overcomes limitations of single-agent therapy.
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
This combination therapy aims to enhance in vivo efficacy, reduce side effects, and improve the safety profile by selectively targeting cancer cells, thereby potentially overcoming the limitations of existing therapies.
Implementation Method 1
A key bottleneck in the de novo pyrimidine synthesis pathway is the enzyme cytidine triphosphate synthase (CTPS) which catalyses the conversion of UTP to CTP
Implementation Method 2
Therapeutic inhibition of BCL2 can be achieved by drugs designed to mimic the activity of the BH3 domain of pro-apoptotic proteins. These drugs induce apoptosis by triggering mitochondrial membrane depolarisation
Data Source
AI summary
The invention provides inter alia methods of treating cancer comprising administering to a subject a cytidine triphosphate synthase 1 (CTPS1) inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor.