ACT001 hydrochloride
ACT001 (Dimethylaminomicheliolide; DMAMCL) hydrochloride is an orally active, blood-brain barrier-permeable anti-inflammatory and anti-tumor agent. ACT001 hydrochloride exerts microglia-mediated neuroanti-inflammatory effects by inhibiting the AKT/NF-κB/NLRP3 axis and suppressing apoptosis (apoptosis). ACT001 hydrochloride inhibits tumor proliferation by upregulating NKTR and inhibiting AKT. ACT001 hydrochloride alleviates metabolic-associated fatty liver disease by regulating gut microbiota and inhibiting ileal FXR. ACT001 hydrochloride inhibits pyroptosis (pyroptosis) and pro-inflammatory cytokine release by activating PPAR-γ and inhibiting NF-κB/NLRP3.
For research use only. We do not sell to patients.
- CAS No.: 1403357-80-1
- Formula: C17H28ClNO3
- Molecular Weight:329.86
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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
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HL-60 | IC50 |
17.2 μM
Compound: 21, DMAMCL
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Cytotoxicity against human HL60 cells after 18 hrs by annexin-V labeling-based flow cytometry
Cytotoxicity against human HL60 cells after 18 hrs by annexin-V labeling-based flow cytometry
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[PMID: 22985027] |
ACT001 (10-40 µM; 28 h) dose-dependently reduces the secretion levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-18) and increases the secretion level of the anti-inflammatory cytokine IL-10 in LPS (HY-D1056)-stimulated NR8383 rat alveolar macrophages[1].
ACT001 (10-40 µM; 28 h) dose-dependently reduces the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-18) and increases the mRNA expression of the anti-inflammatory cytokine IL-10 in LPS-stimulated NR8383 rat alveolar macrophages[1].
ACT001 (10-40 µM; 28 h) dose-dependently reduces the pyroptosis level of LPS-stimulated NR8383 rat alveolar macrophages, as determined by caspase-1 activity assay and PI staining[1].
ACT001 (10-40 µM; 28 h) dose-dependently reduces the protein expression of NLRP3 inflammasome components (NLRP3, ASC) and pyroptosis mediators (caspase-1 p20, GSDMD-N) in LPS-stimulated NR8383 rat alveolar macrophages[1].
ACT001 (10-40 µM; 28 h) dose-dependently upregulates the expression of PPAR-γ in LPS-stimulated NR8383 rat alveolar macrophages and inhibits the activation of the NF-κB pathway (reducing the phosphorylation levels of IκB-α and NF-κB p65), while PPAR-γ inhibitors reverse these anti-inflammatory/anti-pyroptotic effects[1].
ACT001 (0.0625-800 μM; 72 h) potently inhibits the viability of non-small cell lung cancer (NSCLC) cell lines, with the strongest activity against H1703 cells (IC50 = 9.21 μM) and H1975 cells (IC50 = 14.42 μM) after 72 hours of treatment[2].
ACT001 (10-20 μM; 10-14 days) inhibits the clonal proliferation of H1703 and H1975 non-small cell lung cancer (NSCLC) cells in a dose-dependent manner[2].
ACT001 (10-20 μM) alters gene expression in H1703 non-small cell lung cancer (NSCLC) cells, among which the cell cycle pathway is most significantly affected, and NKTR is one of the most significantly upregulated genes[2].
ACT001 (10-20 μM) induces G1/S cell cycle arrest in H1703 and H1975 non-small cell lung cancer (NSCLC) cells[2].
ACT001 (10-20 μM) downregulates the expression of cyclinD1 and CDK6 in H1703 and H1975 non-small cell lung cancer (NSCLC) cells[2].
ACT001 (10-20 μM) dose-dependently inhibits AKT phosphorylation in H1703 and H1975 non-small cell lung cancer (NSCLC) cells without altering the expression of total AKT[2].
ACT001 (10-20 μM) upregulates the mRNA and protein expression of NKTR in H1703 and H1975 non-small cell lung cancer (NSCLC) cells in a dose-dependent manner[2].
ACT001 (20 μM) upregulates the mRNA and protein expression of NKTR, even in NKTR-knockdown H1703 and H1975 non-small cell lung cancer (NSCLC) cells[2].
ACT001 (1-10 μM; 12-48 h) exhibits no cytotoxicity against mouse microglial BV2 cells at concentrations up to 10 μM and incubation durations of 12-48 h[3].
ACT001 (1-10 μM; 24-48 h) dose-dependently inhibits LPS-induced pro-inflammatory activation of mouse microglial BV2 cells, reduces amoeboid morphological changes and the expression of pro-inflammatory cytokines, and increases the expression of anti-inflammatory cytokines[3].
ACT001 (1-10 μM; 24-48 h) dose-dependently inhibits LPS-induced activation of primary mouse microglia, reduces NO production and the number of CD68+ activated cells, without affecting cell viability[3].
ACT001 (1-10 μM; 24-48 h) dose-dependently inhibits LPS-induced activation of primary rat microglia, reduces NO production and the number of CD68+ activated cells, without affecting cell viability[3].
ACT001 (1-10 μM; 24-48 h) dose-dependently reduces neuronal apoptosis of mouse hippocampal HT22 cells induced by LPS-activated mouse microglial BV2 cells in a Transwell co-culture model, accompanied by decreased NO production[3].
ACT001 (1-2 μM; 24 h) dose-dependently alleviates the inhibitory effect of LPS-activated mouse microglial BV2 cells on angiogenesis of mouse brain endothelial bEnd.3 cells, reduces VEGF levels, and restores the expression of tight junction proteins[3].
ACT001 (1-10 μM; 24 h) inhibits the AKT/NFκB/NLRP3 neuroinflammatory pathway in rat primary microglia and mouse microglial BV2 cells by directly binding to AKT, reducing AKT phosphorylation levels, suppressing NFκB nuclear translocation, and inhibiting NLRP3 inflammasome activation[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NR8383 rat alveolar macrophages
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Concentration:10, 20 and 40 µM (4 h pretreatment followed by 24 h LPS stimulation)
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Incubation Time:4 h pretreatment + 24 h (LPS stimulation)
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Result:Significantly decreased secretion of proinflammatory cytokines TNF-α, IL-6, IL-1β, and IL-18 compared to LPS-only treatment.
Increased secretion of anti-inflammatory cytokine IL-10 compared to LPS-only treatment.
Exhibited dose-dependent effects on cytokine secretion.
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Cell Line:NR8383 rat alveolar macrophages
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Concentration:10, 20 and 40 µM (4 h pretreatment followed by 24 h LPS stimulation)
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Incubation Time:4 h pretreatment + 24 h (LPS stimulation)
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Result:Significantly decreased mRNA expression of proinflammatory cytokines TNF-α, IL-6, IL-1β, and IL-18 compared to LPS-only treatment.
Increased mRNA expression of anti-inflammatory cytokine IL-10 compared to LPS-only treatment.
Exhibited dose-dependent effects on cytokine gene expression.
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Cell Line:NR8383 rat alveolar macrophages
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Concentration:10, 20 and 40 µM (4 h pretreatment followed by 24 h LPS stimulation)
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Incubation Time:4 h pretreatment + 24 h (LPS stimulation)
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Result:Significantly reduced expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N in a dose-dependent manner compared to LPS-only treatment.
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Cell Line:NR8383 rat alveolar macrophages
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Concentration:10, 20 and 40 µM (4 h pretreatment followed by 24 h LPS stimulation); 40 µM (with PPAR-γ inhibitor pretreatment)
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Incubation Time:4 h pretreatment + 24 h (LPS stimulation); 4 h PPAR-γ inhibitor pretreatment + 4 h ACT001 pretreatment + 24 h (LPS stimulation)
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Result:Upregulated PPAR-γ expression and downregulated phosphorylation of IκB-α and NF-κB p65 in a dose-dependent manner compared to LPS-only treatment.
Reversed these effects when co-treated with PPAR-γ inhibitor T0070907, decreasing PPAR-γ expression and increasing phosphorylation of IκB-α and NF-κB p65.
Increased expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N compared to ACT001-only treatment when co-treated with PPAR-γ inhibitor.
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Cell Line:human NSCLC cell lines NCI-H1703, NCI-H1975
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Concentration:10 and 20 μM
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Incubation Time:10-14 days
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Result:Significantly reduced the number of colonies formed by both cell lines in an increasing concentration-dependent manner.
Reduced colony number by ~50% relative to control in H1703 cells treated with 10 μM, and by ~70% with 20 μM.
Reduced colony number by ~40% relative to control in H1975 cells treated with 10 μM, and by ~60% with 20 μM.
All reductions were statistically significant.
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Cell Line:murine microglia BV2 cells
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Concentration:1, 2, 5 and 10 μM
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Incubation Time:12, 24, 36 and 48 h
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Result:Failed to significantly reduce cell viability over 12-48 hours, with viability remaining near 100% of control levels.
Caused only a minor reduction in viability at 10 μM after 48 hours.
Induced dose- and time-dependent decreases in cell viability at concentrations exceeding 10 μM.
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Cell Line:murine hippocampal HT22 cells (in BV2-HT22 Transwell co-culture model with LPS-activated murine microglia BV2 cells)
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Concentration:1, 2, 5 and 10 μM
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Incubation Time:12, 24, 36 and 48 h
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Result:Reduced NO production in co-culture supernatants in a dose-dependent manner.
Reversed HT22 cell apoptosis induced by LPS-activated BV2 cells in a dose-dependent manner.
ACT001 (200 mg/kg; p.o.; once daily; for 12 consecutive days) hydrochloride significantly inhibits the growth of non-small cell lung cancer xenografts in BALB/c nude mice, upregulates NKTR expression, downregulates Ki67 expression, and causes no hepatotoxicity or nephrotoxicity[2].
ACT001 (100 mg/kg; p.o.; once daily; for 7 consecutive days) hydrochloride reduces the lesion volume induced by traumatic brain injury (TBI) by 5.36% in male C57BL/6 mice on day 7 post-injury. It improves blood-brain barrier (BBB) integrity and promotes neurobehavioral recovery by inhibiting microglial activation and neuronal apoptosis[3].
The neuroprotective efficacy of ACT001 (100 mg/kg; p.o.; once daily; for 7 consecutive days) hydrochloride is significantly reduced in male C57BL/6 mice with traumatic brain injury (TBI) whose microglia are depleted by PLX5622[3].
ACT001 (200 mg/kg/d; oral administration; daily dosing; for 20 consecutive weeks) hydrochloride alleviates metabolic dysfunction-associated steatotic liver disease (MASLD) induced by high-fat diet (HFD) in female C57BL/6J mice, significantly reduces hepatic aspartate transaminase (AST) and triglyceride (TG) levels, restores intestinal barrier function, modulates gut microbiota, and regulates the bile acid-FXR-FGF15 axis[4].
ACT001 (200 mg/kg/d; oral administration; daily dosing; for 6 consecutive weeks) hydrochloride alleviates MCD-induced MASLD in female C57BL/6J mice, significantly reduces the levels of intestinal inflammatory markers, modulates the gut microbiota, and regulates the bile acid-FXR-FGF15 axis[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (5-6 weeks old)[2]
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Dosage:200 mg/kg
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Administration:p.o.; daily; 12 days
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Result:Reduced subcutaneous tumor volumes significantly compared to controls.
Increased NKTR expression significantly in tumor xenografts.
Reduced Ki67 expression significantly in tumor xenografts.
Showed no detectable hepatic or renal toxicity via HE staining of liver and kidney tissue.
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Animal Model:C57BL/6 (male, 8-12 weeks old, 20-25 g, TBI induced via controlled cortical impact)[3]
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Dosage:100 mg/kg
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Administration:p.o.; daily; 7 days
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Result:Reduced ipsilateral cortex lesion volume by 5% at 7 days post-TBI.
Decreased Evans blue leakage in the ipsilateral cortex at 7 days post-TBI.
Lowered modified Neurological Severity Score (mNSS) at 14 days post-TBI.
Reduced ratio of left foot faults in the Grid-Walking Test at 14 days post-TBI.
Increased time on the Rotarod Test at 14 days post-TBI.
Raised average score in the Hanging Wire Test at 14 days post-TBI.
Reduced the number of Iba1+/CD68+ activated microglia in the peri-contusion region at 7 days post-TBI.
Reduced the number of NeuN+/TUNEL+ apoptotic neurons in the peri-contusion region at 7 days post-TBI.
Improved continuity of BBB tight junction proteins (ZO-1 and Occludin) at 7 days post-TBI.
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Animal Model:C57BL/6 (male, 8-12 weeks old, 20-25 g, TBI induced via controlled cortical impact, microglia depleted via 14 days of PLX5622 diet prior to CCI)[3]
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Dosage:100 mg/kg
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Administration:p.o.; daily; 7 days
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Result:Showed significantly higher mNSS scores at 14 days post-TBI compared to ACT001-treated mice without microglial depletion.
Increased ratio of left foot faults in the Grid-Walking Test at 14 days post-TBI compared to ACT001-treated mice without microglial depletion.
Reduced time on the Rotarod Test at 14 days post-TBI compared to ACT001-treated mice without microglial depletion.
Lowered average score in the Hanging Wire Test at 14 days post-TBI compared to ACT001-treated mice without microglial depletion.
Had more extensive extravasated blood in the ipsilateral cortex at 7 and 14 days post-TBI compared to non-depleted, ACT001-treated mice.
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Animal Model:C57BL/6J (female, 8 weeks old, 20 g, high-fat diet-induced)[4]
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Dosage:200 mg/kg/d
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Administration:p.o.; daily; 20 weeks
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Result:Reduced hepatic aspartate transaminase (AST), triglyceride (TG), and total cholesterol (TC) levels, with statistically significant improvements in AST and TG.
Mitigated liver damage, lipid deposition, and hepatocyte swelling, with greater improvement in liver damage than the reference drug PPC.
Restored expression of intestinal tight junction proteins (ZO-1, Occludin, Claudin-1) and significantly reduced intestinal TNF-α mRNA levels.
Enriched Verrucomicrobia phylum and Akkermansia genus; reversed HFD-induced reductions in Clostridium and Erysipelotrichaceae_Clostridium, and HFD-induced increases in Sutterella and Rikenella.
Increased levels of 23-Nor-Deoxycholic Acid (23-DCA), 5-β-Cholanic Acid-3α-ol-6-one (6-ketoLCA), Isolithocholic Acid (ILCA), and Lithocholic Acid-3-Sulfate (LCA-3S); decreased levels of conjugated BAs.
Significantly downregulated elevated ileal fibroblast growth factor 15 (FGF15) mRNA expression and significantly upregulated hepatic cholesterol 7α-hydroxylase (CYP7A1) mRNA expression.
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Animal Model:C57BL/6J (female, 8 weeks old, 20 g, methionine-choline-deficient diet-induced)[4]
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Dosage:200 mg/kg/d
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Administration:p.o.; daily; 6 weeks
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Result:Improved liver macroscopic appearance (color and texture) and reduced hepatic lipid droplet size and inflammatory infiltration.
Significantly reduced intestinal IL-6 and TNF-α mRNA levels and partially restored expression of intestinal tight junction proteins (ZO-1, Occludin, Claudin-1).
Enriched Bacteroidetes phylum and Bacteroides genus; reduced MCD-induced increases in Tenericutes phylum, Bifidobacterium, and Shigella; elevated relative abundances of Streptococcus, Enterococcus, Erysipelotrichaceae_Clostridium, Clostridium, Adlercreutzia, Subdoligranulum, cc_115, and Gemella.
Increased levels of 23-DCA, LCA-3S, and Chenodeoxycholic Acid (CDCA).
Significantly downregulated elevated ileal FGF15 mRNA expression, significantly upregulated hepatic CYP7A1 mRNA expression, and significantly increased hepatic bile salt export pump (BSEP) mRNA expression.
Chemical Information
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CAS No. 1403357-80-1
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Molecular Weight 329.86
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Formula C17H28ClNO3
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SMILES
C[C@@]1([C@]2([H])[C@]3([H])[C@](CCC(C)=C2CC1)([H])[C@@H](C(O3)=O)CN(C)C)O.Cl
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Synonyms
Dimethylaminomicheliolide hydrochloride; DMAMCL hydrochloride
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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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