APL180
APL180 (L-4F) is an Apo-A1 mimetic peptide. APL180 binds oxidized/oxidizable lipids with high affinity and sequesters pro-inflammatory oxidized lipids. APL180 downregulates glycolysis-related genes and HIF-1α expression, and upregulates CD206 and Arginase. APL180 inhibits atherosclerotic lesion progression and platelet aggregation. APL180 attenuates adverse left ventricular remodeling and systolic dysfunction after myocardial infarction. APL180 can be used for research on ovarian cancer.
For research use only. We do not sell to patients.
- CAS No.: 388566-97-0
- Formula: C114H156N24O28
- Molecular Weight:2310.60
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
HIF-1α |
In Vitro
In thioglycolate-elicited C57BL/6 peritoneal macrophages, APL180 (50 µg/mL; overnight) suppresses M1 inflammatory/glycolytic markers and augments HIF-2α in M1-polarized cells without affecting M2-polarized HIF-2α[2].
In RAW 264.7 mouse macrophages, APL180 (50 µg/mL; overnight) suppresses M1-associated iNOS/CCL3 and glycolytic/HIF-1α markers while upregulating CD206 and arginase in M1-polarized cells[2].
APL180 (150-1,000 ng/mL) ex vivo dose-dependently improves the HII in human plasma samples, with 150 ng/mL sufficient to sequester most HII-affecting oxidized lipids[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW 264.7 mouse macrophage cell line
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Concentration:50 µg/mL
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Incubation Time:overnight
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Result:L-4F significantly reduced expression of iNOS and CCL3 in M1-polarized RAW 264.7 cells.
L-4F significantly augmented expression of CD206 and arginase in M1-polarized RAW 264.7 cells compared with M0-polarized cells.
Significantly downregulated glycolytic gene and HIF-1α expression in M1-polarized cells.
Did not affect HIF-2α expression in M2-polarized macrophages.
In Vivo
APL180 (100 µg/day; i.v. via tail vein; once daily; 5 consecutive days) does not alter cardiac function or monocyte/macrophage profiles in sham-operated mice[2].
APL180 (5 mg/kg; i.p.; before ethanol gavages) does not produce behavioural changes in female Wistar rats subjected to alcohol binge drinking[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 10-12 weeks of age)[2]
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Dosage:100 µg/day in 200 µL PBS
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Administration:i.v. via tail vein; once daily; 5 consecutive days
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Result:Echocardiography: L-4F prevented progressive LV chamber dilatation and dysfunction; changes in LV EDV, ESV, and EF from day 3 to day 8 were smaller than in PBS-treated MI mice.
Representative LV volumes: PBS 3 days post-MI 61 µL and 8 days post-MI 88 µL; L-4F 3 days post-MI 60 µL and 8 days post-MI 65 µL.
Blood: PBS-treated MI mice had nearly 3-fold increased Ly6Chi monocytes versus sham; L-4F suppressed Ly6Chi monocytosis to levels comparable to sham.
No significant L-4F-mediated effects on circulating Ly6Clow monocytes in MI mice.
Spleen: PBS-treated MI mice had ~2-fold increased frequency of pro-inflammatory Ly6Chi monocytes in the spleen at 8 days post-MI versus sham; L-4F suppressed and normalized this.
Augmented spleen weight in MI mice versus L-4F-treated sham-operated mice.
Heart macrophages: L-4F suppressed pro-inflammatory F4/80+Ly6Chi macrophages in post-MI hearts without significant effects on F4/80+Ly6Clow macrophages.
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Animal Model:C57BL/6J (male, 10-12 weeks of age)[2]
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Dosage:100 µg/day in 200 µL PBS
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Administration:i.v. via tail vein; once daily; 5 consecutive days
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Result:Echocardiography: no differences between pre-administration LV EDV, ESV, and EF; no meaningful changes in EDV, ESV, and EF over time after either L-4F or PBS administration.
Blood: circulating Ly6Chi and Ly6Clow monocytes were comparable regardless of group.
Heart macrophages: L-4F had no effect on macrophages in sham-operated hearts.
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Animal Model:Wistar (female, 200-225 g)[3]
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Dosage:5 mg/kg
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Administration:i.p.; 15 min before alcohol gavages
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Result:4F administration showed no behavioural changes.
Exogenous administration of the ApoAI mimetic peptide had no effect on alcohol binge drinking-induced alterations during abstinence.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 388566-97-0
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Molecular Weight 2310.60
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Formula C114H156N24O28
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Synonyms
L-4F
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Sequence
Ac-Asp-Trp-Phe-Lys-Ala-Phe-Tyr-Asp-Lys-Val-Ala-Glu-Lys-Phe-Lys-Glu-Ala-Phe-NH2
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Sequence Shortening
Ac-DWFKAFYDKVAEKFKEAF-NH2
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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)
Keywords
- APL180
- 388566-97-0
- L-4F
- APL 180
- APL-180
- HIF/HIF Prolyl-Hydroxylase
- Arginase
- Apolipoprotein
- HDL inflammatory index inhibitor
- atherosclerotic lesion
- hematopoietic stem cell
- lipid sequestrant
- macrophage plasticity
- monocyte chemoattractant protein
- monocyte migration
- myocardial infarction
- ovarian cancer
- oxidized lipids
- Inhibitor
- inhibitor
- inhibit