Histone Methyltransferase Inhibitors & Menin-MLL Disruptors for MLL-Rearranged and NPM1-Mutant Acute Leukemias. High-purity recombinant SET domains, interaction partners, and lentiviral systems for next-generation epigenetic drug development.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for KMT2A/MLL drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Enzyme Target | KMT2A/MLL SET Domain Recombinant Protein Active methyltransferase domain (residues 3765-3969), Sequence Verified, >95% purity, HEK293 expressed. |
View KMT2A Products |
| PPI Partner | MEN1 (Menin) Recombinant Protein Full-length binding partner for MLL complex interaction assays, High Purity (>95%). |
View MEN1 Products |
| Complex Component | WDR5 Recombinant Protein WD40 repeat protein, critical for MLL complex assembly, Endotoxin <1EU/µg. |
View WDR5 Products |
| Gene Delivery | KMT2A Lentivirus Premade Particles Full-length ORF or SET domain for stable cell line construction in leukemia models. |
View KMT2A Products |
| Benchmark Ab | Anti-KMT2A/MLL Recombinant Antibody Sequence-defined positive control for Western/IP, validated for ChIP compatibility. |
View KMT2A Products |
| Validator | KMT2A/MLL siRNA Set (3 unique sequences) For specific knockdown verification in MLL-r leukemia cell lines. |
View KMT2A Products |
| Related Target A | MEN1 (Menin) Direct binding partner; co-target for MLL-Menin disruption strategies. |
View MEN1 Products |
| Related Target B | WDR5 Core COMPASS subunit essential for KMT2A methyltransferase assembly. |
View WDR5 Products |
| Related Target: DOT1L | DOT1L Recombinant Protein Downstream methyltransferase in MLL-rearranged leukemia; synergy target. |
View DOT1L Products |
| Selectivity Panel | KMT2B SET Domain Protein Paralog for selectivity screening (avoid KMT2B toxicity), Sequence Verified. |
View KMT2B Products |
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| KMT2 Family Selectivity (KMT2B/C/D off-target) | Homolog Panel Available: Human KMT2A, KMT2B, KMT2C, KMT2D SET domains with >95% purity, identical expression systems (HEK293) for consistent assay kinetics. |
| Menin-MLL PPI Disruption Validation | Truncated MLL1 peptides (residues 2826-2930) and Full-length MEN1 protein for AlphaScreen/SPR assay development. |
| Cellular Context (Nuclear Entry) | Lentivirus for Stable Cell Lines: KMT2A wild-type and MLL-AF9 fusion constructs in leukemia cell models; preserve native chromatin context. |
| Resistance Mutation Screening | Menin Mutant Proteins (MEN1 V101G, F27A, A59T) and KMT2A interface variants for mechanistic resistance studies. |
| Drug Resistance Modeling | Human/Mouse orthologs and site-directed mutant recombinant proteins available with >95% purity. |
| Lack of Assay Controls | Clinical-grade benchmark antibodies and Menin protein pairings available. |
Live KMT2A/MLL R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
- ➤ View Active Clinical Trials for KMT2A/MLL-r Leukemia
- ➤ Menin-MLL Inhibitor Trials (Revumenib, Ziftomenib)
- ➤ Latest Resistance Research
- ➤ Recent Patent Filings
Global Clinical Landscape & Future Outlook
The race for KMT2A/MLL-targeted therapeutics has shifted decisively toward Menin-MLL protein-protein interaction (PPI) disruption, with first-generation inhibitors (revumenib, ziftomenib) showing clinical efficacy in MLL-rearranged and NPM1-mutant acute leukemias. As these agents advance through Phase II/III, the next wave of R&D focuses on direct SET domain inhibitors (addressing resistance mutations at the Menin interface) and PROTAC degraders capable of eliminating both wild-type and fusion oncoproteins. Key players include Syndax (Revumenib, Phase III), Kura Oncology (Ziftomenib, Phase II), Johnson & Johnson (JNJ-75276617), Biomea Fusion (BMF-219), and Daiichi Sankyo (DS-1594). The field is increasingly differentiating between MLL-rearranged leukemia (dependent on Menin-MLL interaction) and solid tumor applications, where KMT2A wild-type function may require distinct inhibition strategies. Combination therapies with BCL-2 inhibitors (Venetoclax), FLT3 inhibitors, and DOT1L inhibitors are being actively explored to overcome resistance and improve durable responses.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Menin-MLL Inhibitor (Small Molecule) | Syndax (Revumenib), Kura Oncology (Ziftomenib), J&J (JNJ-75276617), Biomea Fusion (BMF-219) | MLL-r AML/ALL, NPM1-mutant AML | PPI Disruption Assay: MEN1 + MLL1 peptide (2826-2930) with High Purity (>95%) for AlphaScreen/FP |
| Direct SET Domain Inhibitor | Daiichi Sankyo (DS-1594), Discovery-stage programs | Refractory AML, Solid Tumors | Enzymatic Activity Assay: Full SET domain with proper cofactor (SAM) binding; Selectivity panel vs KMT2B required |
| PROTAC Degrader | Preclinical (Universities, Biotech) | MLL-r Leukemia, MDS | Cell-Based Degradation: Lentivirus-expressed KMT2A-Fusion constructs for t1/2 measurements |
| Combination (Menin + DOT1L) | Various Academia | High-Risk MLL-r | Dual Target Validation: KMT2A + DOT1L proteins for mechanistic synergy studies |
| WDR5-MLL Inhibitor | Discovery Phase / Academia | Solid Tumors, AML | Selectivity Assay (Need structural homolog proteins) |
Key Functional Domains & Mutations
Based on UniProt Q03164, KMT2A contains the following key domains: SET domain (catalytic), Bromo domain, FYR N-terminal, FYR C-terminal. Clinically relevant mutations include dbSNP:rs9332745, rs9332747, and rs9332772, which are documented in UniProt. These mutations may impact drug binding or protein stability and are critical for resistance modeling.
This integrated analysis combines knowledge from multiple intelligence streams to provide a comprehensive, non-redundant overview of the KMT2A/MLL landscape.