Market Intelligence, Clinical Progress, and High-Purity Reagents for Metabolic Disease and Oncology Development.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for AMPK Alpha 1 drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Active Kinase | PRKAA1 (AMPK Alpha 1) Kinase Domain (1-550), Active Human, GST-tag, T172 phosphorylated, High purity (>90%), Kinase Assay Ready. |
View PRKAA1 Products |
| Inactive Mutant | PRKAA1 T172A Kinase Dead Mutant Sequence Verified, ATP-binding competent but catalytically inactive, Negative control. |
View PRKAA1 Products |
| Isoform Selectivity Panel | PRKAA2 (AMPK Alpha 2) Kinase Domain Human, His-tag, For alpha 1 vs alpha 2 counter-screening. |
View PRKAA2 Products |
| Gene Delivery | PRKAA1 Lentivirus Particles CMV promoter, Puromycin resistance, Full-length ORF for stable cell line generation. |
View PRKAA1 Products |
| Phospho-Specific Ab | Anti-Phospho-AMPK Alpha (Thr172) Rabbit monoclonal, Recombinant, For detection of activated kinase. |
View PRKAA1 Products |
| Knockdown Validator | PRKAA1 siRNA Set (3 unique sequences) For isoform-specific knockdown and specificity confirmation. |
View PRKAA1 Products |
| Complex Component A | PRKAB1 (AMPK Beta 1) Full Length Scaffold subunit, required for heterotrimeric complex assembly. |
View PRKAB1 Products |
| Complex Component B | PRKAG1 (AMPK Gamma 1) Full Length Nucleotide binding subunit, CBS domain containing. |
View PRKAG1 Products |
| Upstream Kinase | LKB1 (STK11) Active Kinase Domain For in vitro phosphorylation and activation assays. |
View LKB1 Products |
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| α1/α2 Isoform Selectivity Screening | Matched pair of Human PRKAA1 and PRKAA2 recombinant kinase domains with identical tags and purity specs (>90%), enabling direct IC50 comparison. |
| Activation State Dependence | Phosphorylated T172 (Active) vs T172A mutant (Inactive) protein pair for mechanistic validation of allosteric vs ATP-competitive inhibitors. |
| Heterotrimeric Complex Assembly | PRKAB1 and PRKAG1 full-length proteins available for in vitro reconstitution of native AMPK complexes. |
| Cellular Context (LKB1-deficient models) | PRKAA1 Lentivirus for stable integration into HEK293 or HepG2 backgrounds with defined LKB1 status. |
| Phospho-Specific Detection | Anti-pT172 antibody with no cross-reactivity to unphosphorylated form or PRKAA2 (when appropriately selected). |
Live AMPK Alpha 1 R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
Global Clinical Landscape & Future Outlook
The race for AMPK-targeted metabolic therapeutics has pivoted sharply following the clinical discontinuation of pan-AMPK activators like MK-8722, which demonstrated robust glucose-lowering efficacy but induced dose-limiting cardiac hypertrophy attributed to Alpha 2 isoform activation in cardiomyocytes. This safety signal has catalyzed a strategic shift toward Alpha 1 isoform-selective activation (PRKAA1) or tissue-restricted delivery mechanisms to spare cardiac tissue. Current front-runners including Poxel Pharma's Imeglimin (O304 mechanism) and next-generation direct activators are prioritizing liver-specific Alpha 1 engagement for Type 2 Diabetes and NASH. The competitive landscape is additionally fragmented by mechanism-of-action divergence: allosteric ADaM site activators (A-769662 analogs) versus nucleotide pocket binders, and emerging PROTAC approaches targeting regulatory complexes.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Pan-AMPK Activators | Merck (MK-8722 - discontinued), AstraZeneca | Type 2 Diabetes (historical) | Alpha 1/Alpha 2 Selectivity Panel (Need PRKAA1 vs PRKAA2 proteins) |
| Alpha-1 Selective Small Molecules | Poxel Pharma (O304), Novo Nordisk | T2D, NASH, HFpEF | Isoform-specific Kinase Assays (Need PRKAA1 T172-phosphorylated Active protein) |
| Metformin-like Indirect Activators | Multiple Generic/Research Programs | Metabolic Syndrome, Cancer | Cellular Energy Stress Models (Need PRKAA1 Lentivirus for LKB1-deficient lines) |
| AMPK Complex PROTACs | Emerging Academic/Startups | Cancer (metabolic reprogramming) | Heterotrimeric Complex Proteins (Need PRKAB1/PRKAG1 for ternary complex formation) |
Key Mutations and Functional Domains
- Protein Kinase Domain: The catalytic domain of PRKAA1 is essential for kinase activity, as evidenced by UniProt Q13131.
- dbSNP:rs17855679: A key mutation in PRKAA1, documented in UniProt Q13131 VAR_058401.
- dbSNP:rs928784854: A somatic mutation found in a breast cancer sample, documented in UniProt Q13131 VAR_035622.
Future Directions and Assay Strategy
Future R&D will focus on tissue-specific activation for NASH/MASH and targeted AMPK inhibitors for oncology contexts where metabolic stress adaptations drive tumor resistance. Key assay needs include isoform selectivity panels, activation state dependence (using T172A mutants), and heterotrimeric complex assembly for native AMPK reconstitution. TarMart provides high-purity (>95%), sequence-verified recombinant proteins and matched pairs for precise counter-screening, ensuring robust and reproducible results.