ATB1071
ATB1071 is a brain-penetrant and orally active p62/SQSTM1 activator. ATB1071 binds to the p62-ZZ domain, promotes PB1-dependent p62 self-polymerization, and activates p62-mediated mitophagy. ATB1071 can be used for the research of Leigh syndrome, cerebral ischemia-reperfusion injury[1].
For research use only. We do not sell to patients.
- CAS No.: 2921556-65-0
- Formula: C25H27F2NO4
- Molecular Weight:443.48
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
ATB1071 (1 mM; 2 h) engages the p62-ZZ domain to promote PB1-dependent p62 oligomerization in HeLa cell lysates[1].
ATB1071 activates p62-dependent selective autophagy in SH-SY5Y cells without engaging canonical AMPK activation or mTOR inhibition[1].
ATB1071 (2.5-10 μM) induces p62-dependent, autophagy-lysosome-mediated clearance of damaged mitochondria selectively under mitochondrial stress in SH-SY5Y cells, with dose-dependent activity at 2.5-10 μM[1].
ATB1071 induces mitophagy in mt-mKeima HeLa cells via a Parkin-independent pathway under Rotenone (HY-B1756)-induced stress, and enhances Parkin-mediated mitophagy under CCCP (HY-100941)-induced stress[1].
ATB1071 activates mitophagy and restores mitochondrial bioenergetic function in NDUFS4-knockdown SH-SY5Y cells, reversing MMP depolarization, ROS elevation, and ATP deficiency[1].
ATB1071 (2-5 μM; 8-24 h) enhances the interaction between p62 and NIPSNAP1 in HEK293T cells, particularly under mitochondrial stress, via a mechanism dependent on the p62 ZZ/PB1 axis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | AUClast | T1/2 | Bioavailability | Brain-to-Plasma Ratio |
|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | p.o. | 5750.6 ng·h/mL | 9.8 h | 70.4 % | 2.12 % |
ATB1071 (10 mg/kg; i.p.; at 0, 3, 24, and 48 hours post-MCAO) provides robust neuroprotection and restores neurological function after cerebral ischemia-reperfusion injury primarily via EBP1-dependent mitophagy[1].
ATB1071 (10 mg/kg; i.p.; at 0, 3, 24, and 48 hours post-MCAO) has its mediated mitophagy restored by reintroduction of EBP1, which enhances neuroprotection and functional recovery after cerebral ischemia-reperfusion injury in Ebp1-deficient mice[1].
ATB1071 (p.o.; daily for 1 week or 3 times per week for 2 weeks) exhibits NOAEL of at least 30 mg/kg and 300 mg/kg in ICR mice and rats, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:B6.129S4-Ndufs4m1.1Rpa/J mice (Ndufs4-/-; starting at postnatal day 10); wild-type/heterozygous control mice (starting at postnatal day 10)[1]
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Dosage:10 mg/kg
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Administration:i.p.; every other day; 40 days
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Result:Increased TOM20+LC3+ proximity ligation assay puncta in the deep cerebellar nuclei and olfactory bulb of Ndufs4-/- mice.
Elevated p62 levels by ~1.8-fold and its oligomeric/aggregated species by ~2.4-fold in the brain mitochondrial fraction.
Reduced GFAP+ astrocytes and Iba1+ microglia.
Lowered expression of inflammation-associated genes (Cd14, Il-1β, S100a8).
Extended median survival by ~31% and maximal lifespan by ~64% relative to vehicle-treated Ndufs4-/- mice.
Improved forelimb grip strength by ~34% at postnatal day 40.
Increased rotarod latency to fall by ~3-fold at postnatal day 50.
Delayed the onset of clasping/twisting by ~12%.
Reduced skin inflammation-associated hair loss severity scores from 2 to 1.22 at postnatal day 20.
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Animal Model:Pa2g4flox/flox mice (control; aged 6-8 weeks); CamK2-Cre;Pa2g4flox/flox mice (neuron-specific Ebp1 knockout, Ebp1 CKO; aged 6-8 weeks)[1]
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Dosage:10 mg/kg
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Administration:i.p.; at 0, 3, 24, and 48 hours post-MCAO
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Result:Decreased TOM20 levels, increased p62 and LC3-II levels, and enhanced recruitment of LC3+ phagophores to TOM20+ mitochondria in the hippocampus of control MCAO mice.
Reduced infarct volume by ~85% in control MCAO mice.
Lowered neuronal death in the CA1 region by ~91% in control MCAO mice.
Increased rotarod latency to fall from 54.7 to 207.4 seconds in control MCAO mice.
Enhanced four-limb grip strength by ~1.3-fold and forelimb grip strength by ~1.6-fold in control MCAO mice.
Increased total open-field travel distance from 1919 to 2579 cm in control MCAO mice.
Raised Y-maze spontaneous alternation rate from 53% to 83% in control MCAO mice.
Blunted effects in Ebp1 CKO mice, with only ~46% infarct volume reduction, ~40% neuronal death reduction, and no significant improvements in motor, behavioral, or cognitive functions.
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Animal Model:CamK2-Cre;Pa2g4flox/flox mice (neuron-specific Ebp1 knockout, Ebp1 CKO; aged 6-8 weeks)[1]
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Dosage:10 mg/kg
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Administration:i.p.; at 0, 3, 24, and 48 hours post-MCAO
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Result:Restored ATB1071-induced mitophagy in Ebp1 CKO mice via EBP1 reintroduction, as shown by increased LC3 and p62 levels and enhanced mitochondrial localization of LC3 in the hippocampus.
Reduced infarct volume by ~67% (vs ~52% in mock-expressing mice).
Lowered neuronal death by ~86% relative to the mock group.
Improved rotarod performance by ~2.2-fold.
Increased four-limb grip strength by ~1.5-fold and forelimb grip strength by ~1.5-fold.
Increased ambulatory activity by ~1.5-fold.
Improved working memory by ~33% compared with mock-expressing Ebp1 CKO mice.
Chemical Information
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CAS No. 2921556-65-0
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Molecular Weight 443.48
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Formula C25H27F2NO4
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SMILES
OCCNCCCOC1=CC(OCC2=CC=C(F)C=C2)=C(OCC3=CC=C(F)C=C3)C=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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