Anti-androgen Peptides Target Src Kinase SH3 Domain
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Solution Overview
Problem
Current therapies for prostate and breast cancers that target the androgen receptor (AR) often become ineffective due to drug resistance and have undesirable side effects, necessitating the development of specific, non-toxic compounds that can abolish the AR/Src association to inhibit cancer cell growth.
Innovation Solution
Novel synthetic peptides with proline stretches that bind to the SH3 domain of Src kinase, preventing AR interaction and activation, thereby inhibiting AR/Src association and exhibiting anti-tumor activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-androgen therapies are used to target the androgen receptor in prostate and breast cancers, then cancer cell growth is inhibited initially, but drug resistance develops and therapies become ineffective over time
Solution Approach 1:
The patent introduces a peptide intermediary that specifically binds to the SH3 domain of Src kinase, preventing the formation of the AR-Src complex. This peptide acts as a mediator to block the interaction between the androgen receptor and Src kinase, thereby inhibiting downstream signaling pathways that lead to cancer cell proliferation and drug resistance development.
Solution Approach 2:
The invention extracts and targets a specific molecular interaction (AR-Src association) that is critical for cancer progression and therapy resistance. By isolating this specific interaction as the therapeutic target, the patent develops a more precise intervention strategy that addresses the root mechanism of resistance without affecting other cellular processes.
2Object-affected harmful factors
If conventional anti-androgen compounds are administered to block androgen receptor activity, then tumor growth is suppressed, but undesirable side effects occur
Solution Approach 1:
The patent applies local quality by designing a peptide that specifically targets the SH3 domain of Src kinase, a localized molecular structure involved in the AR-Src interaction. This localized targeting approach allows the therapy to act precisely at the site of pathological interaction without broadly affecting other cellular functions, thereby reducing systemic side effects.
Solution Approach 2:
The invention changes the molecular parameter of interaction by using a peptide-based approach instead of traditional small molecule anti-androgens. This parameter change in the therapeutic agent's structure and mechanism allows for more selective binding and reduced off-target effects, improving the therapeutic index.
3Productivity
If androgen ablation therapy is used to treat prostate cancer, then initial response is positive in over 80% of patients, but disease progression occurs in a median of 12 to 18 months due to hormone refractory state
Solution Approach 1:
The patent employs preliminary action by blocking the AR-Src interaction early in the disease process, preventing the molecular events that lead to hormone refractory state. By interfering with this critical signaling pathway before resistance develops, the therapy aims to extend the effective treatment duration and delay disease progression beyond the typical 12-18 month timeline.
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 peptides effectively reduce AR activity and DNA synthesis in cancer cells, demonstrating anti-tumor effects in both in vitro and in vivo models, offering a potential alternative to existing therapies with reduced side effects.
Implementation Method 1
The peptides effectively reduce AR activity and DNA synthesis in cancer cells, demonstrating anti-tumor effects in both in vitro and in vivo models
Data Source
AI summary
The present invention relates to isolated or purified or partially purified peptide derived molecules having the following general formula (S1): X-[(Pro)n-His-Pro-His-Ala-Arg-Ile-Lys]m-Y. The peptides are for medical use, in particular as anti-tumoral agents.