Selective MAP4K1 Inhibitor Compounds for Immune Response Modulation

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Solution Overview

Problem

There is a need for new compounds that can selectively modulate MAP4K1 activity for the treatment of MAP4K1-dependent diseases or disorders such as cancer and viral infection, as existing treatments are inadequate.

Innovation Solution

Development of compounds represented by specific chemical formulas (Formulae I-VII) and their pharmaceutically acceptable salts, which inhibit MAP4K1 activity, thereby enhancing immune responses and treating associated diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing treatments are used, then current therapeutic options are available, but they are inadequate for treating MAP4K1-dependent diseases

Engineering Contradiction:

Improvetreatment efficacyVSAvoidtreatment applicability to MAP4K1-dependent diseases

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops novel chemical compounds with specific molecular structures (Formulae I-VII) that target MAP4K1 kinase activity. By changing the chemical parameters and structural properties of the compounds, they achieve selective inhibition of MAP4K1 with IC50 values in the nanomolar range, providing effective treatment for MAP4K1-dependent diseases where existing treatments failed

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent segments the broad class of kinase inhibitors into a specific subset that selectively targets MAP4K1. By designing compounds with specific structural features (substituents at positions R1-R12, ring systems, linker groups L1-L2), the invention isolates MAP4K1 inhibition from other kinase activities, enabling targeted therapy for diseases dependent on MAP4K1 signaling

Inventive Principle:

Principle #1Segmentation

2Reliability

If MAP4K1 activity is attenuated, then anti-tumor immunity is enhanced, but autoimmunity may be contributed to

Engineering Contradiction:

Improveanti-tumor immunityVSAvoidautoimmunity risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by creating compounds with specific spatial arrangements of functional groups that confer selective binding to MAP4K1's active site. The molecular structure features (specific ring systems, substituent positions, stereochemistry) ensure the inhibitor binds locally to MAP4K1 without affecting other kinases, allowing attenuation of MAP4K1 activity for anti-tumor immunity while minimizing broad immune suppression that could cause autoimmunity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses small molecule inhibitors as intermediaries to modulate MAP4K1 activity. These compounds act as mediators that can be precisely controlled in dosage and duration, allowing therapeutic attenuation of MAP4K1 to enhance anti-tumor immunity while the ability to control the intermediary's presence and concentration helps manage the risk of autoimmunity

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20260103475A1Map4k1 inhibitors

Publication Date: 2026.04.16 BLUEPRINT MEDICINES CORP

AI summary

One embodiment of the disclosure is a compound represented by Formula I or a pharmaceutically acceptable salt thereof. The variables in Formula I are defined herein.Compounds of Formula I are MAP4K1 inhibitors, which can be used to treat a diseases or disorders in a subject that benefits from control of MAP4K1 activity.