LSD1 Inhibitor Combinations for Synergistic Solid Tumor Therapy

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Solution Overview

Problem

Current LSD1 inhibitors, such as Tranylcypromine, exhibit undesired side effects due to MAO-A inhibition, necessitating the development of cyclopropylamine derivatives with potent LSD1 inhibitory activity and reduced MAO-A inhibitory activity for effective cancer treatment.

Innovation Solution

Combining LSD1 inhibitors with specific active pharmaceutical ingredients, such as ABT-199, ABT-263, and Veliparib, to achieve additive or synergistic effects in inhibiting cancer cell growth in vitro and in vivo.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current LSD1 inhibitors such as Tranylcypromine are used, then LSD1 inhibitory activity is achieved, but MAO-A inhibition causes undesired side effects

Engineering Contradiction:

ImproveLSD1 inhibitory activityVSAvoidMAO-A inhibition side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the inhibitory activity into two separate components: LSD1 inhibition (desired) and MAO-A inhibition (undesired). By designing cyclopropylamine derivatives that selectively inhibit LSD1 while sparing MAO-A, the invention isolates the therapeutic effect from the harmful side effects, resolving the technical contradiction between reliability of LSD1 inhibition and harmful MAO-A inhibition effects.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by creating compounds with selective inhibitory properties - the cyclopropylamine derivatives exhibit potent LSD1 inhibition in specific cellular contexts (cancer cells) while maintaining minimal MAO-A inhibition. This localized selectivity allows the drug to act precisely on the target enzyme without affecting other enzymes, thereby achieving reliable LSD1 inhibition without the harmful side effects of MAO-A inhibition.

Inventive Principle:

Principle #3Local quality

2Ease of operation

If single-agent LSD1 inhibitors are used, then treatment simplicity is maintained, but cancer treatment efficacy is limited

Engineering Contradiction:

Improvetreatment simplicityVSAvoidcancer treatment efficacy

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent merges LSD1 inhibitors with other anti-cancer agents (such as ABT-199, ABT-263, Veliparib, and platinum-based drugs) to create combination therapies. This merging of multiple therapeutic mechanisms produces synergistic or additive effects that significantly enhance cancer treatment efficacy compared to single-agent therapy, while the combined regimen remains clinically manageable.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent employs composite therapeutic strategies by combining LSD1 inhibitors (cyclopropylamine derivatives) with other pharmacologically active compounds. This composite approach leverages the unique mechanism of LSD1 inhibition alongside other anti-cancer mechanisms, creating a multi-faceted therapeutic effect that overcomes the limitations of single-agent therapy and improves overall treatment efficacy.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS12564559B2Combinations of LSD1 inhibitors for use in the treatment of solid tumors

Publication Date: 2026.03.03 ORYZON GENOMICS SA

AI summary

The instant invention relates to therapeutic combinations of LSD1 inhibitors and one or more other active pharmaceutical ingredient(s) or pharmaceutically acceptable salts thereof. The combinations are particularly useful for treating neoplastic diseases, such as cancer, particularly small cell lung cancer (SCLC).