1. Apoptosis NF-κB Metabolic Enzyme/Protease Immunology/Inflammation
  2. Ferroptosis Keap1-Nrf2 FOXO NO Synthase Quinone Reductase
  3. NPB-1575

NPB-1575 is a potent, orally active and brain-penetrant anti-inflammatory agent. NPB-1575 mitigates neuroinflammation and resists ferroptosis by activating the IRS2/Nrf2/NF-κB axis. NPB-1575 shows protective effect against cerebral ischemic injury and improve the neurological functional prognosis. NPB-1575 can be used for the study of ischemic stroke.

For research use only. We do not sell to patients.

NPB-1575 Chemical Structure

NPB-1575 Chemical Structure

CAS No. : 161984-54-9

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Description

NPB-1575 is a potent, orally active and brain-penetrant anti-inflammatory agent. NPB-1575 mitigates neuroinflammation and resists ferroptosis by activating the IRS2/Nrf2/NF-κB axis. NPB-1575 shows protective effect against cerebral ischemic injury and improve the neurological functional prognosis. NPB-1575 can be used for the study of ischemic stroke[1].

In Vitro

NPB-1575 (1-10 μM, 6 h) exhibits anti-inflammatory effects by activating Nrf2 and inhibiting FOXO1 via IRS2/Akt signaling in LPS-stimulated BV2 cells[1].
NPB-1575 (1-10 μM, 12 h) attenuates inflammatory response in primary microglia cells via upregulating IRS2[1].
NPB-1575 (10 μM, 12 h) inhibits ferroptosis in ischemic stroke via upregulating IRS2 In the primary neuron-microglia transwell cell model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: LPS (HY-D1056) (1 μg/mL)-stimulated BV2 microglial cells
Concentration: 1, 3, 10 μM
Incubation Time: Cultured for 6 h and then stimulated with LPS for 6 h
Result: Significantly reduced iNOS and Iba1 protein expression dose-dependently.
Significantly increased IRS2 and phosphorylation of AKT.
Increased the levels of Nrf2, HO-1 and NQO-1 concentration-dependently.
Markedly reduced the levels of total FOXO1 and nucleus FOXO1.
Be blocked by IRS2 knockout, FOXO1 overexpression, LY294002(HY-10108) and ML385 (HY-100523).
Reduced NO and TNF-α releases.

Western Blot Analysis[1]

Cell Line: Primary neuron-microglia transwell cell, following LPS stimulation
Concentration: 1, 3, 10 μM
Incubation Time: 12 h
Result: Reversed the ferroptosis of neurons.
Regulated the levels of TFR1, ACSL4, SLC7A11 and GPX4.
In Vivo

NPB-1575 (25 mg/kg, p.o., single dose after surgery) attenuates neuroinflammation during cerebral ischemia and resist ferroptosis through the IRS2 in pMCAO rats[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Permanent occlusion of middle cerebral artery (pMCAO) model established in Male Sprague-Dawley rats with a weight of 260–280 g[1]
Dosage: 25 mg/kg
Administration: Oral gavage (p.o.), 5 min to 4 h after surgery (pMCAO), and behavioral recovery (limb-placing test, rotarod) at 3, 7, and 28 days post-pMCAO.
Result: Reduced the cerebral infarction volume of rats at 3 and 7 days after pMCAO.
Showed significant improvement in behavioral recovery up to 28 days after pMCAO.
Significantly increased level of IRS2 and the protein expression in the brain tissue.
Significantly reduced the levels of CD68, iNOS and NF-κB.
Persistent suppression of microglial activation (Iba1) and pro-inflammatory cytokines (TNF-α, IL-6).
Promoted AKT phosphorylation, raised Nrf2, HO-1, and NQO-1 levels and reduced FOXO1 expression.
Improved TFR1, ACSL4 and SLC7A11 and GPX4 levels via IRS2 and the effects were reversed by IRS2 knockdown.
Molecular Weight

314.38

Formula

C19H22O4

CAS No.
SMILES

OC1=CC(O)=C(C/C=C(C)/C)C(CCC2=CC(O)=C(O)C=C2)=C1

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Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

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NPB-1575
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HY-174807
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