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.
For research use only. We do not sell to patients.
- CAS No.: 1820750-36-4
- Formula: C21H33N3O5
- Molecular Weight:407.50
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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
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- References
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Biological Activity
Description
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COX-2 |
iNOS |
TLR4 |
NLRP3 |
Microbial Metabolite |
In Vitro
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.
In Vivo
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 No. 1820750-36-4
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Molecular Weight 407.50
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Formula 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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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
[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
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LYRM03 Related Classifications
HY-N19847 Related Classifications
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