HATC
HATC is a HIF-1α AUTAC degrader. HATC links HIF-1α to LC3 to form a ternary complex that undergoes degradation via the autophagy-lysosome fusion pathway. HATC induces dose-dependent HIF-1α degradation in multiple cell types. HATC reduces visceral fat accumulation, hepatic lipid deposition, senescent cell aggregation, and bone loss; alleviates age-related intervertebral disc degeneration, liver dysfunction, kyphosis, and alveolar dilation; decreases circulating lactic acid levels; improves physical performance; and reverses age-related changes in granulocyte proportions. HATC extends median and maximum lifespan, reduces transcriptomic age, and causes no obvious persistent toxicity. HATC can be used in the research of age-related diseases (pink: LC3 ligand (HY-50759); blue: HIF-1α ligand (HY-P10426); Linker: (HY-W008264)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C79H102ClN13O13
- Peso molecular:1477.19
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
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HIF-1α |
HATC (1-2 μM) potently induces autophagic degradation of HIF-1α in NP cells at 5% oxygen with no cytotoxicity at concentrations up to 2 μM[1].
HATC induces autophagic degradation of HIF-1α in 293T and HeLa cells under hypoxic conditions[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Plasma Concentration |
|---|---|---|---|
| Mice[1] | 20 mg/kg | i.p. | 0.3 μM |
HATC (20 mg/kg; i.p.; once weekly) reduces HIF-1α levels and alleviates lumbar spine instability-induced accelerated intervertebral disc aging in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J mice (male and female, aged 20 months at treatment initiation)[1]
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Dosage:20 mg/kg
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Administration:i.p.; once weekly; until natural death
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Result:Extended median lifespan by 14% and maximum lifespan by 12.1% compared to vehicle.
Mitigated age-associated weight gain and prevented rapid terminal weight loss, maintaining stable body weight until late life.
Reduced HIF-1α levels across multiple organs (lung, spleen, liver) compared to vehicle-treated aged mice.
Lowered predicted transcriptomic age in 24-month-old mice, with transcriptomic changes showing upregulation of pathways linked to improved organ function and metabolic health.
Reduced abdominal visceral fat accumulation and hepatic lipid deposition, prevented age-related increases in serum alanine aminotransferase and aspartate aminotransferase levels, and lowered circulating lactate levels to near young-mouse levels.
Improved multiple physical performance metrics (grip strength, maximal walking speed, bean balance time, hanging endurance, daily activity) to values approaching young mice.
Reduced age-related bone mass loss in female mice, improved spinal kyphosis index (lower spinal curvature), and attenuated age-dependent alveolar volume expansion in the lungs.
Reduced P16INK4a-positive senescent cells in organs, decreased inflammatory cell invasion in lung and liver, lowered circulating levels of SASP markers (IL-6, G-CSF), and reversed age-related increases in granulocyte proportion.
Reduced spontaneous tumor incidence by ~20% compared to vehicle-treated mice.
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Animal Model:mice (aged 9 months at treatment initiation, LSI-induced aging model)[1]
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Dosage:20 mg/kg
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Administration:i.p.; once weekly; 3 months
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Result:Significantly reduced HIF-1α levels in IVDs within 2 weeks of treatment initiation.
Alleviated age-related disc degeneration, as shown by improved histological scores on Safranin O/Fast Green staining, higher T2-weighted MRI signal intensity in IVDs, increased paw withdrawal threshold (reduced low back pain), and reduced P16INK4a-positive senescent cell accumulation in IVDs compared to vehicle-treated LSI mice.
Caused no overt toxicity or tissue damage in major organs (lung, spleen, liver) as assessed by H&E staining.
Chemical Information
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Peso molecular 1477.19
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Fòrmula C79H102ClN13O13
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SMILES
O=C1N(CC2=CC=CC=C2)C([C@@H](C(C)C)N(CCCNC(CCOCCOCCOCCN3C=C(C[C@H](NC([C@H](CC4=CC=C(O)C=C4)N5)=O)C(N[C@@H](CC(C)C)C(N[C@@H](CC(C)C)C(N[C@@H](CC6=CC=CC=C6)C(N[C@@H](C(C)C)C5=O)=O)=O)=O)=O)N=N3)=O)C(C7=CC=C(C)C=C7)=O)=NC8=CC(Cl)=CC=C18
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
HATC Related Classifications
HY-184158 Related Classifications
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