3,4-Dihydroquinazoline Derivative Blocks Calcium Influx to Arrest Cancer Cell Cycle

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Solution Overview

Problem

Current cancer treatments face challenges such as side effects on normal cells and drug tolerance, limiting the effectiveness of targeted therapy and existing anti-cancer drugs, necessitating a novel agent that can enhance treatment efficacy by blocking T-type calcium channels in cancer cells.

Innovation Solution

A 3,4-dihydroquinazoline derivative or its pharmaceutically acceptable salt, which acts as a T-type calcium channel blocker, is developed to inhibit intracellular calcium influx in cancer cells, arresting the cell cycle and enhancing the efficacy of existing anti-cancer drugs when used in combination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If targeted therapy is used to reduce side effects on normal cells, then side effects are reduced, but drug tolerance develops and efficacy diminishes over time

Engineering Contradiction:
Improveside effects on normal cellsVSAvoiddrug efficacy
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent employs alternating treatment cycles between targeted therapy and chemotherapy to prevent drug tolerance. The 3,4-dihydroquinazoline derivative is administered in periodic cycles with existing anti-cancer drugs, allowing the cancer cells to not adapt to a single therapeutic mechanism continuously, thereby maintaining efficacy while managing side effects through scheduled treatment intervals

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent combines the 3,4-dihydroquinazoline derivative (a T-type calcium channel blocker) with existing anti-cancer drugs to create a composite therapeutic approach. This combination therapy addresses drug tolerance by engaging multiple cellular pathways simultaneously - the calcium channel blocking action complements the mechanisms of existing drugs, producing synergistic effects that overcome resistance while maintaining targeted therapy's reduced side effect profile

Inventive Principle:
Principle #40Composite materials

2Reliability

If existing anti-cancer drugs are used continuously to treat cancer, then initial treatment efficacy is achieved, but drug tolerance develops reducing long-term effectiveness

Engineering Contradiction:
Improveinitial treatment efficacyVSAvoidlong-term treatment effectiveness
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent introduces dynamic treatment protocols where the 3,4-dihydroquinazoline derivative is combined with existing anti-cancer drugs in varying ratios and sequences. This dynamic approach allows adjustment of therapeutic strategies based on treatment response, preventing cancer cells from developing fixed resistance patterns and extending the duration of effective treatment

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The 3,4-dihydroquinazoline derivative acts as an intermediary agent that enhances the action of existing anti-cancer drugs through calcium channel blocking. This intermediary mechanism prevents drug tolerance by interfering with calcium-dependent survival pathways in cancer cells, thereby extending the effective duration of treatment with existing drugs

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If targeted therapy is applied selectively based on specific targeted molecules, then treatment precision is improved, but applicability is limited to patients with specific molecular markers

Engineering Contradiction:
Improvetreatment precisionVSAvoidpatient applicability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent makes the 3,4-dihydroquinazoline derivative a universal anti-cancer agent that can be combined with multiple different existing anti-cancer drugs targeting various cancer types and mechanisms. This multi-functional approach allows the compound to enhance the efficacy of different targeted therapies and chemotherapy agents, expanding patient applicability across various cancer indications while maintaining precision through mechanism-based selection

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 3,4-dihydroquinazoline derivative effectively induces cell cycle arrest in cancer cells, providing strong synergistic anti-cancer activity when combined with existing drugs, thereby overcoming drug tolerance and enhancing treatment outcomes for various types of cancer.

Implementation Method 1

Calcium plays a critical role as an intracellular signal, and controls various cell processes, of which calcium appears to play an important role in cell growth. For example, calcium signaling is required for cell cycle progression from G1 phase to S phase during mitosis, and the depletion of intracellular calcium arrests the cell cycle in the transition of G0/G1 into S phase.

Methodology Applied
Scientific EffectCalcium signaling:

Implementation Method 2

Regulation of the intracellular calcium amount has been proposed to be via a T-type calcium channel. Lined with this proposition, it has recently been reported that T-type calcium channel blockers (CCBs) inhibited cellular proliferation

Methodology Applied
Scientific EffectT-type calcium channel blocking:

Data Source

PatentEP3150584B13,4-dihydroquinazoline derivative and complex preparation containing same
Publication Date: 2018.09.26 UNIVERSITY INDUSTRY COOPERATION GROUP OF KYUNG HEE UNIVERSITY

AI summary

The present invention relates to a 3,4-dihydroquinazoline derivative or a pharmaceutically acceptable salt thereof, which can block the intracellular influx of calcium ions acting as a secondary signal essential to the proliferation and growth of cancer cells, thereby inducing the cell cycle arrest of cancer cells, and eventually reinforcing the efficacy of existing anti-cancer drugs, and a combination comprising the above compound and another anti-cancer drug.