MS41

Target: This ligand targets eleven-nineteen leukemia protein ENL/MLLT1 bromodomain in biochemical or cellular target-engagement studies.

Mechanism of Action: Used as the target-protein recognition element, this ligand provides the binding interface for eleven-nineteen leukemia protein ENL/MLLT1 bromodomain. In PROTAC design, a derivatizable position on the ligand can be connected through an optimized linker to an E3 ligase ligand, such as a CRBN, VHL, or IAP recruiter, while preserving productive target engagement. The resulting bifunctional molecule brings eleven-nineteen leukemia protein ENL/MLLT1 bromodomain into proximity with the recruited E3 ligase, enabling ternary-complex formation. If the complex has favorable geometry and residence time, target lysine ubiquitination is promoted, leading to proteasome-dependent degradation in experimental systems.

• PROTAC-Mediated BRD Degradation: MS41 can be used as a ligand module to build PROTACs that recruit an E3 ligase and drive selective ubiquitination of BRD-family targets. In targeted protein degradation workflows, MS41-containing chimeras help evaluate degradation potency, proteasome dependence, and cellular selectivity compared with occupancy-based inhibition approaches.

• E3 Ligase Recruitment Optimization: Incorporating MS41 into PROTAC architectures enables systematic tuning of linker length, attachment chemistry, and E3 ligase engagement to maximize target turnover. Researchers can use MS41-based chimeras to compare degradation efficiency across ligase choices, assess ternary complex stabilization, and map structure–activity relationships governing productive ubiquitination.

• Mechanism-of-Action Profiling: MS41-derived PROTACs support mechanistic studies distinguishing degradation from mere inhibition. By combining MS41 PROTAC treatment with proteasome or neddylation pathway perturbations, investigators can quantify pathway dependence, characterize kinetics of target loss, and determine whether degradation requires efficient ubiquitin transfer.

• Proteome-Selective Degradation Studies: MS41 can be leveraged to design PROTACs aimed at achieving controlled selectivity within BRD-associated networks. In PROTAC research, MS41-containing constructs can be paired with proteomic readouts to evaluate off-target degradation patterns, identify compensatory pathway activation, and refine ligand–linker strategies for improved specificity.

Structure: The structure of MS41 is characterized by primary or secondary amine/basic nitrogen centers; amide/urea/sulfonamide hydrogen-bonding motifs; phenol or alcohol functionality; heteroaromatic protein-recognition scaffold. These features provide defined hydrogen-bonding, hydrophobic, and steric elements that can support affinity retention while enabling analogue-based linker-vector selection.

Reactivity: The amine/basic nitrogen-containing motif can be evaluated for acylation, sulfonylation, alkylation, or carbamate/urea linker installation when that vector is solvent exposed. For PROTAC construction, the POI ligand can be paired with CRBN ligands such as thalidomide, pomalidomide, or lenalidomide analogues, VHL ligands such as VH032 derivatives, or less common IAP/MDM2/cIAP-recruiting ligands, with alkyl, PEG, piperazine, triazole, or amide linkers screened for ternary-complex formation. In practice, incorporation into PROTACs should begin from derivatives that preserve the reported binding pharmacophore, followed by systematic variation of linker length, polarity, rigidity, and exit-vector geometry to optimize target engagement, E3 recruitment, and cellular degradation readouts.