Kidney-Targeted Peptide Compounds for Selective Renal Cancer Therapy

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Solution Overview

Problem

Current anticancer drugs for renal cell carcinoma (RCC) and metastatic RCC exhibit high levels of adverse effects due to cytotoxicity, leading to toxicity in healthy tissues and organs, necessitating the development of safer therapies with improved selectivity for cancerous cells.

Innovation Solution

Novel compounds comprising acyclic and cyclic peptides with a kidney-affinity structure and a cytotoxic payload, designed for targeted delivery and release specifically at the cancer site, minimizing exposure to healthy tissues and utilizing enzymatic or chemical cleavage for controlled payload release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cytotoxic anticancer drugs are used to treat renal cell carcinoma, then therapeutic effect against cancer cells is achieved, but severe toxicity to healthy tissues and organs occurs

Engineering Contradiction:

Improvetherapeutic effectVSAvoidtoxicity to healthy tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The anticancer drug is segmented into two functional components: a kidney-targeting moiety that directs the compound to renal tissue, and a cytotoxic payload that provides the therapeutic effect. This segmentation allows the toxic agent to be delivered only to the intended target (kidney cancer cells) while sparing healthy tissues, thereby maintaining therapeutic efficacy while reducing systemic toxicity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

A kidney-targeting moiety acts as an intermediary that mediates between the cytotoxic payload and kidney cancer cells. This intermediary component binds specifically to receptors or structures on kidney cancer cells, facilitating selective delivery of the toxic agent to the cancer cells while preventing off-target effects on healthy tissues

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If standard-of-care drugs like sunitinib are administered to achieve optimal anticancer effect, then cytotoxic effect on cancer cells is achieved, but hematotoxicity and bone marrow suppression occur

Engineering Contradiction:

Improveanticancer effectVSAvoidhematotoxicity

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The compound exhibits local quality by concentrating the cytotoxic effect specifically in kidney tissue through the kidney-targeting moiety. The drug's pharmacological activity is localized to the kidney, where it can exert its anticancer effect on renal cell carcinoma without causing systemic hematotoxicity or bone marrow suppression that characterizes conventional cytotoxic agents

Inventive Principle:

Principle #3Local quality

3Reliability

If axitinib is used to treat renal cancer, then anticancer therapeutic effect is achieved, but severe hypertension and cardiac failure occur

Engineering Contradiction:

Improveanticancer therapeutic effectVSAvoidcardiac toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The harmful cardiovascular side effects are extracted from the therapeutic effect by removing the systemic circulation exposure. The kidney-targeting moiety extracts the drug from the systemic circulation and delivers it directly to kidney cancer cells, taking out the toxic effects (hypertension, cardiac failure) from the therapeutic equation while preserving the anticancer activity

Inventive Principle:

Principle #2Taking out (Extraction)

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

These compounds achieve selective and safer anticancer therapy with reduced adverse effects on normal organs, demonstrating enhanced targeting and efficacy against kidney cancer cells while minimizing toxicity to healthy tissues.

Implementation Method 1

The compounds of formula I and compositions thereof are selectively taken up by kidney cancer cells, with or without subsequent endocytosis

Methodology Applied

Scientific EffectEndocytosis:

Implementation Method 2

designed for targeted delivery and release specifically at the cancer site, minimizing exposure to healthy tissues and utilizing enzymatic or chemical cleavage for controlled payload release

Methodology Applied

Scientific EffectEnzymatic cleavage: Enzyme

Data Source

PatentUS20230141981A1Novel compounds and composition for targeted therapy of kidney-associated cancers

Publication Date: 2023.05.11 SHANGHAI MICURX PHARMACEUTICAL CO LTD

AI summary

The present invention provides therapeutic compounds of the following formula I: or pharmaceutically acceptable salts, hydrates, or solvates thereof that are therapeutic or anticancer agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.