MDM2-FLT3 Combination Therapy for Resistant AML Treatment

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Solution Overview

Problem

Current cancer therapies, particularly for acute myeloid leukemia (AML) with FLT3 gene mutations, face challenges in effectively targeting the p53 antagonist MDM2 and FLT3 kinase, leading to poor prognosis in unfit, refractory, or relapsed patients.

Innovation Solution

A pharmaceutical combination of compounds M and N, represented by specific structures, is used to inhibit MDM2 and FLT3 kinase, potentially restoring p53 tumor suppressor function and providing a novel therapeutic approach for cancer treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a single anti-cancer agent is used, then the treatment is simple and well-tolerated, but the therapeutic effect is limited and resistance develops

Engineering Contradiction:
Improvetherapeutic effectVSAvoidtreatment complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines two anti-cancer agents with different mechanisms of action into a single pharmaceutical composition. The first agent targets DNA damage response pathways while the second agent targets protein synthesis, creating a synergistic effect that overcomes resistance mechanisms and enhances therapeutic efficacy compared to single-agent therapy.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If high doses of anti-cancer agents are administered, then therapeutic effect increases, but side effects and toxicity increase

Engineering Contradiction:
Improvetherapeutic effectVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the dosage parameters of two anti-cancer agents administered simultaneously at lower individual doses than would be required for monotherapy. By adjusting the concentration parameters and administration timing, the composition achieves enhanced therapeutic effect through synergistic interaction while maintaining toxicity levels within acceptable clinical ranges.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If anti-cancer treatment is intensified, then tumor control improves, but quality of life deteriorates

Engineering Contradiction:
Improvetumor controlVSAvoidquality of life
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent introduces a multi-component pharmaceutical composition as an intermediary system that mediates between aggressive anti-cancer therapy and patient tolerance. The composition includes agents with complementary mechanisms that work synergistically to achieve effective tumor control at reduced individual dosages, thereby improving quality of life while maintaining therapeutic efficacy.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP3999056B1Pharmaceutical combination and its use in the prevention and treatment of cancer
Publication Date: 2026.05.06 ASCENTAGE PHARMA SUZHOU CO LTD
  • EP3999056B1 patent drawingFigure 1~2
  • EP3999056B1 patent drawingFigure 3
  • EP3999056B1 patent drawing

AI summary

The invention discloses a novel pharmaceutical combination and a use thereof. The pharmaceutical combination comprises a compound of formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof; and a compound of formula (II), a pharmaceutically acceptable salt thereof or a solvate thereof. The pharmaceutical combination can be used to treat cancer.