Market Intelligence, Preclinical Progress, and High-Purity Reagents for ARHGAP45 (Minor Histocompatibility Antigen HA-1) Drug Discovery.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for ARHGAP45 drug discovery, covering both its immunological role as HA-1 and its RhoGAP signaling function. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Antigen | ARHGAP45 (HA-1) Peptide-HLA Complex / Full-Length Recombinant Protein High purity (>95%), Endotoxin <1 EU/μg. Sequence Verified. Available in His-tag, GST-tag, or native forms (HEK293 expressed). |
View ARHGAP45 Products |
| Mutant Control | ARHGAP45 GAP Domain Mutant (Arginine Finger Mutant) Catalytically inactive variant for mechanistic controls. Also includes HA-1 epitope point mutants (e.g., rs1801284, rs2074442, rs7251797). Sequence verified. |
View ARHGAP45 Products |
| Gene Delivery | ARHGAP45 Promise-ORF / Lentivirus Full-length ORF for stable cell line construction in migration/invasion assays or TCR-T target cell generation. |
View ARHGAP45 Products |
| Benchmark Ab/TCR | Anti-ARHGAP45 Recombinant Reference Antibody / Recombinant TCR (HA-1/HLA-A*02:01) Sequence-verified positive control for binding assays and Western Blot. |
View ARHGAP45 Products |
| Validator | ARHGAP45 siRNA Set (3 unique sequences) For knockdown verification and specificity controls in cell-based assays. |
View ARHGAP45 Products |
| Substrate / Related Family | RHOA / RAC1 / CDC42 Recombinant Proteins Primary GTPase substrates for GAP activity assays; active (GTP-bound) and inactive (GDP-bound) forms available. |
View RHOA Products / View RAC1 Products / View CDC42 Products |
| Related Target A | HLA-A (especially HLA-A*02:01) Major histocompatibility complex presenting the HA-1 peptide. Essential for TCR-T and bispecific antibody development. |
View HLA-A Products |
| Related Target B | CD3E Coreceptor for bispecific T-cell engager (TCE) cross-linking. |
View CD3E Products |
| Related Target C | ARHGAP21 / ARHGAP24 / ARHGAP44 (GRAF1) Homolog panel for selectivity counter-screening. Mass spec verified identities. |
View ARHGAP21 Products / View ARHGAP24 Products / View ARHGAP44 Products |
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| TCR Specificity & Cross-Reactivity (HA-1 context) | High-purity HLA-peptide monomers/tetramers strictly verified by mass spectrometry and SEC for native conformation. |
| GAP Activity Measurement (GTP Hydrolysis) | High-purity ARHGAP45 (>95%) with validated RhoA binding domain; low endotoxin ensures no interference in enzymatic assays. |
| Catalytic Mechanism Validation | Arginine-finger mutant proteins available as negative controls; sequence-verified active site integrity. |
| Selectivity vs ARHGAP Family | Homolog panel (ARHGAP21, ARHGAP24, ARHGAP44) available for counter-screening; mass spec verified identities. |
| Cross-species Preclinical Evaluation | Human / Mouse / Cynomolgus ortholog proteins available, sequence verified. |
| Lack of Reliable Controls | Recombinant positive control TCRs, high-affinity antibodies, and catalytic mutants included. |
| False Positives in Screening | Validated siRNA sets for orthogonal specificity checks in cell-based assays. |
Live ARHGAP45 R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
Global Clinical Landscape & Future Outlook
ARHGAP45, also known as Minor Histocompatibility Antigen HA-1 (HMHA1) and GRAF3, occupies a dual role in drug discovery: (1) as a well-characterized minor histocompatibility antigen exclusively expressed in hematopoietic cells, making it a prime target for T-cell therapy (TCR-T, bispecific T-cell engagers) in post-transplant relapse of leukemia and other hematological malignancies; (2) as a Rho GTPase activating protein (RhoGAP) that negatively regulates RhoA, Rac1, and Cdc42, controlling cytoskeletal dynamics in cancer metastasis, immune cell migration, and neuroinflammation. The field is currently at the preclinical–translational interface, with academic centers leading TCR-T programs targeting the HA-1 peptide/HLA-A*02:01 complex, while early-stage biotechs explore small-molecule inhibitors and protein degraders (PROTACs) against the GAP domain. The next wave of R&D is expected to prioritize off-the-shelf TCR-NK therapies, isoform-selective inhibitors, and dual-acting modalities that exploit both the immunogenic epitope and the enzymatic activity.
Competitive Modality & Indication Snapshot
| Modality | Representative Players / Focus | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| TCR-T Cell Therapy | Academic Medical Centers (e.g., LUMC), Next-Gen Cell Therapy Biotechs | Leukemia, Post-SCT Relapse | TCR Affinity & Specificity Assay (high-purity Peptide-HLA Complexes) |
| Bispecific T-Cell Engagers (TCE) | Early-stage Immuno-oncology Innovators | Refractory Hematological Malignancies | Heterodimer Binding Validation (Target + CD3E recombinant proteins) |
| Peptide Vaccines | Translational Research Institutes | Leukemia prophylaxis | Epitope Presentation Assay (HEK293 expressed native antigens) |
| Small Molecule Inhibitors | Discovery-Stage Programs | Metastatic Solid Tumors (breast, melanoma) | GAP Activity Inhibition Assay (high-purity ARHGAP45 + RhoA complex) |
| Protein Interaction Disruptors | Academic & Biotech Consortia | Immunology (T cell migration) | Pull-down Assay (full-length native folding) |
| Genetic Modulation (siRNA/CRISPR) | Academic & Early Biotech Consortia | Solid Tumors, Hematologic Malignancies | Stable overexpression lines (Lentivirus) and knockdown validation (siRNA) |
| Targeted Protein Degradation (PROTAC) | Undisclosed Preclinical Labs | Oncology | Full-length recombinant protein for ternary complex formation studies |
Molecular Differentiation & Assay Strategy
To develop a best-in-class ARHGAP45 modulator (whether TCR-T, small molecule, or degrader), differentiation must be achieved across several dimensions:
- Affinity & Selectivity: The TCR or antibody must show high affinity for the HA-1/HLA complex without off-target binding to similar peptides or empty HLA. For small molecules, selectivity against homologs (ARHGAP21, ARHGAP24, etc.) is critical to avoid toxicity. Recommended assay: SPR/BLI kinetic analysis using high-purity pMHC monomers and homolog panels.
- Catalytic Mechanism: For GAP inhibitors, the arginine finger mutant (RxxxA) provides a negative control to confirm on-target activity. Full-length and GAP-domain proteins are needed for conformational integrity.
- Cellular Delivery & Functional Validation: Stable cell lines expressing ARHGAP45 and HLA-A*02:01 (via lentivirus) are essential for cytotoxicity and cytokine release assays. siRNA-based rescue experiments confirm specificity.
- Cross-species Translation: Human, mouse, and cynomolgus orthologs support preclinical efficacy and toxicology studies.
- Degradation Strategy: For PROTACs, ternary complex formation (ARHGAP45-E3 ligase-linker) must be validated using HEK293-expressed full-length protein with native post-translational modifications.
TarMart provides all necessary reagents—high-purity proteins, mutants, lentivirus, siRNA, and control antibodies—to support these assays with guaranteed quality (purity >95%, endotoxin <1 EU/μg, sequence verified).