(4R,5S)-nutlin carboxylic acid

Background Introduction

(4R,5S)-Nutlin carboxylic acid is a key derivative of the nutlin class, renowned for its high affinity toward the MDM2 E3 ubiquitin ligase. Nutlin compounds are small-molecule inhibitors that disrupt the MDM2-p53 interaction and have gained significant traction as E3 ligase-recruiting ligands in the PROTAC (Proteolysis Targeting Chimera) platform. The introduction of a carboxylic acid group in (4R,5S)-nutlin carboxylic acid offers an efficient handle for chemical conjugation, greatly facilitating the design and synthesis of innovative MDM2-based PROTAC molecules.

Mechanism

(4R,5S)-Nutlin carboxylic acid functions by binding selectively to the MDM2 protein, a crucial E3 ubiquitin ligase component in the cellular protein degradation pathway. When incorporated into a PROTAC molecule, it recruits the MDM2 E3 ligase to physically interact with the target protein, leading to ubiquitination and subsequent proteasomal degradation of the target. The carboxylic acid moiety serves as a versatile functional group for linker attachment, ensuring stable and efficient PROTAC assembly.

Applications

(4R,5S)-Nutlin carboxylic acid is an essential building block for the development of MDM2-based PROTACs, opening new avenues for targeted protein degradation in oncology, inflammation, and beyond. Its chemical flexibility supports the synthesis of bifunctional degraders for various research and therapeutic objectives. Practical applications include:

• Construction of PROTACs utilizing MDM2 recruitment for selective protein degradation
• Chemical biology studies investigating p53 pathway modulation and E3 ligase functionality
• Medicinal chemistry and SAR optimization of MDM2-recruiting warheads
• Advanced PROTAC library design for functional genomics and drug discovery projects

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Selective MDM2-p53 interaction inhibitor used for MDM2-based PROTAC design
• Carboxylic acid functionality enables versatile conjugation for targeted protein degradation