Delving into the Latest Updates on ML211 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

LYPLA2

Mechanism

LYPLA2 inhibitors(lysophospholipase 2 inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

The Scripps Research Institute

Active Organization

The Scripps Research Institute

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Polysorbate (PS) degradation in monoclonal antibody (mAb) formulations poses a significant challenge in the biopharmaceutical industry. PS maintains protein stability during drug product's shelf life but is vulnerable to breakdown by low-abundance residual host cell proteins (HCPs), particularly hydrolytic enzymes such as lipases and esterases. In this study, we used activity-based protein profiling (ABPP) coupled with mass spectrometry to identify acyl-protein thioesterase-1 (APT-1) as a polysorbate-degrading HCP in one case of mAb formulation with stability problems. We validated the role of APT1 by matching the polysorbate degradation fingerprint in the mAb formulation with that of a recombinant APT1 protein. Furthermore, we found an agreement between APT1 levels and PS degradation rates in the mAb formulation, and we successfully halted PS degradation using APT1-specific inhibitors ML348 and ML211. APT1 was found to co-purify with a specific mAb via hitchhiking mechanism. Our work provides a streamlined approach to identifying critical HCPs in PS degradation, supporting quality-by-design principles in pharmaceutical development.

100 Deals associated with ML211

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