LYRM03
LYRM03 is a derivative of Ubenimex (HY-B0134) and a Aminopeptidase N inhibitor. LYRM03 is isolated from Streptomyces HCCB10043. LYRM03 inhibits TLR4, MyD88, NLRP3, ASC, NF-κB and p38 MAPK, stabilizes IκB, and suppresses LPS-induced expression of iNOS and COX-2. LYRM03 reduces the levels of inflammatory cytokines and oxidative stress markers, and alleviates pulmonary edema. LYRM03 exhibits anticancer activity against breast cancer. LYRM03 has anti-inflammatory activity. LYRM03 can be used in the research of acute lung injury and breast cancer.
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- CAS. Nr.: 1820750-36-4
- Formel: C21H33N3O5
- Molecular Weight:407.50
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
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COX-2 |
iNOS |
TLR4 |
NLRP3 |
Microbial Metabolite |
LYRM03 (50-200 μM; 6-24 h) does not affect the viability of NR8383 rat alveolar macrophages after 6, 12, or 24 hours of incubation[1].
LYRM03 (50-200 μM; 24 h) dose-dependently reduces LPS-induced increases in TNF-α, IL-1β, and IL-18 levels in NR8383 rat alveolar macrophage cell supernatants after 24 hours of incubation[1].
LYRM03 (50-200 μM; 24 h) dose-dependently inhibits LPS-induced activation of the NF-κB/TLR4/MyD88 signaling pathway in NR8383 rat alveolar macrophage cells after 24 hours of incubation[1].
LYRM03 (50-200 μM; 24 h) dose-dependently inhibits LPS-induced upregulation of the NLRP3 inflammasome in NR8383 rat alveolar macrophage cells after 24 hours of incubation[1].
LYRM03 (50-500 µmol/L; 1 h pre-incubation + 2 h, 4 h, 16 h, 24 h LPS treatment) inhibits LPS-induced inflammatory mediator expression and nitric oxide production in murine alveolar macrophages, with dose-dependent suppression of iNOS, COX-2, and Myd88 at concentrations ranging from 50 to 500 µmol/L[2].
LYRM03 (100 µmol/L; 1 h pre-incubation + 5, 15, 30, 45, 60 min LPS stimulation) suppresses Myd88-dependent TLR4 signaling in murine alveolar macrophages at 100 µmol/L by inhibiting LPS-induced IκB degradation and p38 MAPK phosphorylation[2].
LYRM03 (10-100 μg/mL; 1 h) inhibits APN enzymatic activity in human breast cancer MDA-MB-231 cells by over 50% at concentrations of 50 μg/mL and 100 μg/mL without altering APN protein expression[4].
LYRM03 (10-100 μg/mL; 6-48 h) induces less than 20% cell death in human breast cancer MDA-MB-231 cells at concentrations up to 100 μg/mL and incubation times up to 48 h[4].
LYRM03 (10-100 μg/mL; 6-48 h) does not induce significant apoptosis in human breast cancer MDA-MB-231 cells at concentrations up to 100 μg/mL and incubation times up to 48 h[4].
LYRM03 (10-100 μg/mL; 6-24 h) dose-dependently inhibits the migration of human breast cancer MDA-MB-231 cells in a wound healing assay, with the strongest effect at 100 μg/mL over 24 h[4].
LYRM03 (50-100 μg/mL; 10 days) reduces colony formation by human breast cancer MDA-MB-231 cells at concentrations of 50 μg/mL and 100 μg/mL over 10 days[4].
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 macrophage cell line
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Concentration:50 μM; 100 μM; 200 μM
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Incubation Time:6 h; 12 h; 24 h
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Result:Showed no significant alteration in cell viability in any group treated with LYRM03, with or without LPS stimulation, relative to the Sham group (p > 0.05).
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Cell Line:NR8383 rat alveolar macrophage cell line
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Concentration:50 μM; 100 μM; 200 μM
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Incubation Time:24 h after LPS stimulation
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Result:Reduced LPS-induced elevated levels of TNF-α, IL-1β, and IL-18 in cell supernatants relative to the LPS-only group (p < 0.05).
Exhibited no effect on cytokine levels when used alone.
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Cell Line:murine alveolar macrophages
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Concentration:100 µmol/L (pre-incubation for 1 h, LPS stimulation for 5, 15, 30, 45, 60 min)
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Incubation Time:1 h pre-incubation + 5, 15, 30, 45, 60 min LPS stimulation
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Result:Significantly reduced LPS-induced IκB degradation at 15, 30, and 45 min post-LPS stimulation.
Significantly inhibited LPS-induced p38 MAPK phosphorylation at 15, 30, 45, and 60 min post-LPS stimulation, while total p38 protein levels remained unchanged.
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Cell Line:MDA-MB-231
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Concentration:10 μg/mL; 50 μg/mL; 100 μg/mL
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Incubation Time:6 h; 12 h; 24 h; 48 h
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Result:Detected no significant cleaved PARP expression via western blot.
Showed no significant increase in apoptotic cells in any treated group compared to untreated controls via flow cytometry.
LYRM03 (20 mg/kg; i.p.; single administration) has no detectable effect on lung injury, oxidative stress, inflammation, or NF-κB/TLR4/NLRP3 pathway activity in healthy rats[1].
LYRM03 (10 mg/kg; i.p.) effectively attenuates LPS-induced acute lung injury in male C57BL/6 mice, reducing inflammatory cell infiltration, pro-inflammatory cytokine production, and lung tissue damage via suppression of Myd88-dependent TLR4 signaling[2].
Posttreatment with LYRM03 (5-20 mg/kg; i.p.; administered at 1 and 12 h after LPS) dose-dependently protects against LPS-induced acute lung injury in rats, with the 20 mg/kg dose exerting the strongest effect by inhibiting the NF-κB/MyD88/TLR4 axis, reducing oxidative stress, inflammation, and pulmonary apoptosis[3].
LYRM03 (100 mg/kg; i.p.; 3 times per week) potently reduces lung metastatic foci formation in a SCID mouse model of MDA-MB-231 breast cancer[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley rats (220-250 g; LPS-induced acute lung injury)[1]
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Dosage:5 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:i.p.; at 1 and 12 h after LPS exposure
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Result:Reduced LPS-induced lung injury scores, lung wet/dry weight ratio, and protein content in BALF in a dose-dependent manner.
Decreased LPS-induced increases in myeloperoxidase (MPO) activity in lung tissue, serum malondialdehyde (MDA) levels, and serum levels of TNF-α, IL-1β, and IL-18 in a dose-dependent manner.
Increased serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in a dose-dependent manner.
Inhibited LPS-induced upregulation of TLR4, MyD88, p-IKKα, p-IKKβ, p-IκBα, p-NF-κB protein and mRNA levels, as well as NLRP3, ASC, and caspase-1 protein and mRNA levels in lung tissue in a dose-dependent manner.
Increased lung injury scores when administered at 20 mg/kg alongside siRNA targeting NF-κB p65, TLR4, or NLRP3 compared to rats treated with 20 mg/kg LYRM03 plus LPS alone.
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Animal Model:Sprague-Dawley rats (220-250 g; healthy)[1]
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Dosage:20 mg/kg
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Administration:i.p.; single administration
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Result:Did not alter lung injury scores, lung wet/dry weight ratio, BALF protein content, lung MPO activity, serum MDA, SOD, or GSH-Px levels, or serum TNF-α, IL-1β, or IL-18 levels compared to sham-treated rats.
Did not affect TLR4, MyD88, NF-κB pathway components, or NLRP3 inflammasome protein and mRNA levels in lung tissue.
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Animal Model:C57BL/6 (male, 6-12 weeks old, 22 g, Specific Pathogen-Free, intratracheal LPS-induced ALI)[2]
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Dosage:10 mg/kg
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Administration:i.p.; single dose (4-h groups); two doses, at time of LPS challenge and 12 hours post-challenge (24-h groups)
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Result:Reduced LPS-induced BALF total protein concentration by approximately 32.7% at 4 hours.
Significantly reduced BALF total protein concentration at 24 hours.
Significantly decreased LPS-induced myeloperoxidase (MPO) activity in lung tissue at both 4 and 24 hours.
Attenuated LPS-induced inflammatory cell infiltration and inter-alveolar septal thickening in lung tissue at 4 and 24 hours.
Reduced LPS-induced mRNA expression of TNF-α, IL-1β, IL-6, and MIP-2 in lung tissue to approximately 30% of LPS-only levels at 4 hours.
Significantly decreased BALF concentrations of IL-6 and TNF-α at 4 hours.
Significantly suppressed LPS-induced iNOS and COX-2 protein expression in lung tissue at 24 hours.
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Animal Model:Sprague-Dawley (adult male, 250-300 g, LPS-induced acute lung injury)[3]
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Dosage:5 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:i.p.; administered at 1 and 12 h after LPS
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Result:Reduced lung injury score to 11.50, lung wet-dry weight ratio to 6.311, BALF protein to 75.37 mg/mL at 5 mg/kg.
Reduced lung injury score to 8.205, lung wet-dry weight ratio to 5.750, BALF protein to 61.81 mg/mL at 10 mg/kg.
Reduced lung injury score to 6.700, lung wet-dry weight ratio to 5.580, BALF protein to 52.55 mg/mL at 20 mg/kg.
Reduced BALF TNF-α to 222.6 pg/mL, IL-1β to 394.1 pg/mL, IL-6 to 403.4 pg/mL at 5 mg/kg.
Reduced BALF TNF-α to 129.6 pg/mL, IL-1β to 375.2 pg/mL, IL-6 to 274.1 pg/mL at 10 mg/kg.
Reduced BALF TNF-α to 93.84 pg/mL, IL-1β to 357.7 pg/mL, IL-6 to 271.5 pg/mL at 20 mg/kg.
Reduced pulmonary MPO activity to 0.3043 U/g, serum MDA to 63.33 nmol/mL, and increased serum SOD to 13.16 U/mL, serum GSH-Px to 132.5 U/mL at 5 mg/kg.
Reduced pulmonary MPO activity to 0.2749 U/g, serum MDA to 41.98 nmol/mL, and increased serum SOD to 15.46 U/mL, serum GSH-Px to 162.1 U/mL at 10 mg/kg.
Reduced pulmonary MPO activity to 0.2039 U/g, serum MDA to 30.12 nmol/mL, and increased serum SOD to 19.54 U/mL, serum GSH-Px to 198.8 U/mL at 20 mg/kg.
Reduced serum TNF-α to 90.79 pg/mL, IL-8 to 1125 pg/mL, IL-6 to 345.6 pg/mL at 5 mg/kg.
Reduced serum TNF-α to 58.95 pg/mL, IL-8 to 1040 pg/mL, IL-6 to 283.2 pg/mL at 10 mg/kg.
Reduced serum TNF-α to 53.43 pg/mL, IL-8 to 904.9 pg/mL, IL-6 to 161.5 pg/mL at 20 mg/kg.
Reduced lung protein levels of TLR4 to 2.255, NF-kB to 2.228, and increased IkB-α to 0.5054 at 5 mg/kg.
Reduced lung protein levels of TLR4 to 1.942, HMGB1 to 2.039, MyD88 to 1.775, NF-kB to 2.187, and increased IkB-α to 0.6831 at 10 mg/kg.
Reduced lung protein levels of TLR4 to 1.702, HMGB1 to 1.674, MyD88 to 1.441, NF-kB to 1.852, and increased IkB-α to 0.6996 at 20 mg/kg; corresponding mRNA expression of TLR4, HMGB1, MyD88, and NF-kB was also significantly reduced, while IkB-α mRNA was increased across all doses.
Reduced apoptotic index to 42.99%, Cleaved Caspase 3 protein to 5.544, BAX protein to 4.811, and increased Cleaved PARP protein to 0.5449, Bcl-2 protein to 0.6006 at 5 mg/kg.
Reduced apoptotic index to 33.51%, Cleaved Caspase 3 protein to 3.625, BAX protein to 4.247, and increased Cleaved PARP protein to 0.6978, Bcl-2 protein to 0.7134 at 10 mg/kg.
Reduced apoptotic index to 28.60%, Cleaved Caspase 3 protein to 2.496, BAX protein to 3.385, and increased Cleaved PARP protein to 0.8879, Bcl-2 protein to 0.7743 at 20 mg/kg.
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Animal Model:SCID mice (female)[4]
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Dosage:100 mg/kg
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Administration:i.p.; 3 times per week
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Result:Showed significantly fewer metastatic foci compared to control mice.
Demonstrated better inhibition of lung metastasis than bestatin.
Chemical Information
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CAS. Nr. 1820750-36-4
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Molecular Weight 407.50
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Formel C21H33N3O5
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SMILES
CC[C@H](C)[C@@H](C(O)=O)NC([C@H](C(C)C)NC([C@@H](O)[C@H](N)CC1=CC=CC=C1)=O)=O
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Structure Classification
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Initial Source
Streptomyces parvus HCCB10043
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Wang B, et al. The Defensive Action of LYRM03 on LPS-Induced Acute Lung Injury by NF-κB/TLR4/NLRP3 Signals. J Invest Surg. 2021;34(3):284-296. [Content Brief]
[2]. He HQ, et al. LYRM03, an ubenimex derivative, attenuates LPS-induced acute lung injury in mice by suppressing the TLR4 signaling pathway. Acta Pharmacol Sin. 2017;38(3):342-350. [Content Brief]
[3]. Jiang Q, et al. Posttreatment With LYRM03 Protects Rats From Acute Lung Inflammation Induced by Lipopolysaccharide via Suppressing the NF-κB/MyD88/TLR4 Axis. J Surg Res. 2019;243:316-324. [Content Brief]
[4]. Yang YK, et al. Chemically synthesized LYRM03 could inhibit the metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo. Bioorg Med Chem Lett. 2019 Jul 15;29(14):1719-1726. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
LYRM03 Related Classifications
HY-N19847 Related Classifications
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