Market Intelligence, Clinical Progress, and High-Purity Reagents for Epigenetic Oncology Development.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for KDM5A drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| WT Enzyme | KDM5A (RBP2) Catalytic Domain Recombinant Protein (JmjC, aa 391-580). High purity (>95%), Endotoxin <1 EU/ug, Sequence Verified. | View KDM5A Products |
| Mutant Enzyme (H483A) | Catalytic dead mutant for negative control in demethylation assays. Sequence Verified. | View KDM5A Products |
| Protein Mutant Panel | Additional mutants (e.g., NEDEHC, rs11062385, rs2229353) for resistance profiling. | View KDM5A Products |
| Gene Delivery | KDM5A Full-Length ORF Lentivirus (CMV promoter, puromycin selection). For stable cell line construction. | View KDM5A Products |
| Benchmark Ab | Anti-KDM5A (ChIP-grade, Clone EPR18875). Recombinant rabbit mAb, validated for ChIP-seq, WB, ICC. | View KDM5A Products |
| Validator | KDM5A siRNA Set (3 target-specific siRNAs). For knockdown verification and specificity controls. | View KDM5A Products |
| Paralog Selectivity A | KDM5B (PLU-1) Catalytic Domain Protein. High homology (~65% identity) for selectivity screening. | View KDM5B Products |
| Paralog Selectivity B | KDM5C (JARID1C / SMCX) Catalytic Domain Protein. X-linked disease cross-reference. | View KDM5C Products |
| Complementary Target A | EGFR Recombinant Protein (including T790M, C797S mutants). For combination therapy studies overcoming TKI resistance. | View EGFR Products |
| Complementary Target B | EZH2 Methyltransferase Protein. Synthetic lethality with KDM5A in certain cancers. | View EZH2 Products |
| Pathway Target | MYC Protein. Downstream oncogenic effector regulated by KDM5A; synergy and combination studies. | View MYC Products |
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| Subfamily Counter Screening (KDM5B/C/D off-target) | Human KDM5A, KDM5B, KDM5C, KDM5D catalytic domain proteins; >95% purity; mass spec verified. |
| Drug Resistance Profiling & Negative Controls | WT + H483A mutant pair plus active-site mutant panel; sequence verified. |
| Cellular Target Engagement | Full-length ORF Lentivirus for stable expression; Endotoxin <1 EU/ug. |
| Epigenetic Readout Validation | ChIP-grade antibodies with defined epitope; siRNA set for knockdown correlation. |
| Biochemical Assay Reproducibility | Endotoxin-controlled recombinant proteins; high batch-to-batch consistency for AlphaLISA/TR-FRET. |
Live KDM5A R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
Global Clinical Landscape & Future Outlook
The race for KDM5A (RBP2) therapeutics is intensifying, with major players shifting focus from pan-epigenetic inhibitors to highly selective KDM5A-specific small molecules and targeted PROTAC degraders. Because KDM5A serves both catalytic (demethylase) and structural scaffolding roles in chromatin complexes, merely inhibiting its enzymatic activity is often insufficient. As first-generation KDM5 inhibitors (e.g., CPI-1205 from Constellation) enter early clinical evaluations, the next wave of R&D is aggressively targeting PROTAC-mediated degradation, allosteric modulation, and combination regimens (particularly with EGFR TKIs and EZH2 inhibitors) to eradicate drug-tolerant persister (DTP) cells in solid tumors. Key indications include EGFR-mutant non-small cell lung cancer (NSCLC), ER+ breast cancer, acute myeloid leukemia (AML), and MYC-driven cancers. The field is also anticipating resistance mutations (e.g., at H483, N478, R495) driving demand for custom mutant proteins.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Small Molecule Inhibitor | Bayer, Epizyme/Ipsen, Constellation/MorphoSys, Takeda | Gastric Cancer, NSCLC, AML, Solid Tumors | Enzymatic Assay with JmjC domain; Paralog selectivity panel (KDM5A vs B/C/D) |
| PROTAC Degrader | Arvinas, C4 Therapeutics, Academic Consortia | Refractory Solid Tumors, ER+ Breast Cancer | Target Engagement Assay (full-length protein); Cellular degradation validation (Western Blot with ChIP-grade Ab) |
| Allosteric Modulator | Academic Consortia | Neurodegeneration, Solid Tumors | Conformational Binding Assay (full-length protein with PHD domains) |
| Combination Therapy (Targeted) | AstraZeneca, Daiichi Sankyo | EGFR-TKI Resistant NSCLC, ER+ Breast Cancer | Pathway Combo Screening (KDM5A + EGFR/EZH2 proteins); Resistance modeling with Lentivirus |
| Pan-KDM5 Tool Compound | Academic Labs | Epigenetic Research | Subfamily selectivity panel (KDM5A/B/C/D); WT + mutant pair for mechanism studies |
Key Differentiators & Assay Recommendations
To achieve best-in-class selectivity, drug candidates must demonstrate:
- Paralog selectivity: >50-fold window over KDM5B/C/D. Use TarMart's KDM5A/B/C/D protein panel in TR-FRET/AlphaScreen assays.
- Slow off-rate (residence time) for sustained chromatin occupancy; evaluate via SPR with high-purity JmjC domain.
- Cellular activity: Use H3K4me3 ChIP-qPCR after treatment; confirm target engagement with TarMart's validated antibodies.
- Resistance mutation profiling: Test candidate against clinically relevant variants (e.g., H483A, rs11062385, rs2229353) provided as custom recombinant proteins.
- Cell-based degradation assay (for PROTACs): Use full-length ORF lentivirus to construct stable cell lines and verify degradation by Western blot with MG132 control.
- Off-target liability screening: Include KDM4, KDM6, EZH2, and MYC pathways; TarMart provides orthogonal recombinant proteins.
Reported domains: JmjN, ARID, JmjC (UniProt P29375). Functional mutations in NEDEHC (decreased expression) and dbSNP rs11062385/rs2229353 are available as mutant proteins.