LNO 9
LNO 9 is an orally active LOXL2 inhibitor and NO donor, with an IC50 of 0.17 μM against human LOXL2. LNO 9 competitively binds to the LTQ cofactor of LOXL2 to form an irreversible complex, thereby inhibiting collagen oxidation and abnormal cross-linking. LNO 9 releases nitric oxide (NO) to increase cGMP levels in pulmonary artery smooth muscle cells. LNO 9 inhibits hypoxia-induced collagen modification and possesses vasodilatory activity. LNO 9 ameliorates right ventricular hypertrophy and pulmonary artery medial thickness in rat models induced by hypoxia and Monocrotaline (HY-N0750), and can be used for research on pulmonary hypertension.
For research use only. We do not sell to patients.
- Formula: C23H24F4N4O7
- Molecular Weight:544.45
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
LNO 9 (2 h) exhibits selective inhibition of human LOXL2 over human LOX, LOXL3, SSAO, DAO, MAO-A, and MAO-B, with an LOXL2 IC50 of 0.17 μM[1].
LNO 9 (20-40 μM; 24 h) significantly inhibits hypoxia-induced proliferation of HPASMCs, with efficacy superior to lenumlostat[1].
LNO 9 (20-40 μM; 24 h) significantly inhibits hypoxia-induced migration of HPASMCs, with efficacy superior to lenumlostat[1].
LNO 9 (20-40 μM) modulates sGC, YAP/TAZ, and fibrotic signaling pathways in hypoxia-induced HPASMCs, increasing p-VASP and p-YAP/p-TAZ while reducing PKG1, nuclear YAP/TAZ/TEAD4, α-SMA, collagen I, fibronectin 1, and p-Smad3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Hypoxia-induced human pulmonary arterial smooth muscle cells (HPASMCs)
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Concentration:20-40 μM
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Incubation Time:24 h
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Result:Significantly suppressed hypoxia-induced HPASMC proliferation, with efficacy superior to lenumlostat at equivalent concentrations.
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Cell Line:Hypoxia-induced human pulmonary arterial smooth muscle cells (HPASMCs)
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Concentration:20-40 μM
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Incubation Time:24 h
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Result:Significantly suppressed hypoxia-induced HPASMC migration, with greater efficacy than lenumlostat at equivalent concentrations.
In Vivo
LNO 9 (15-30 mg/kg; p.o.; daily; 14 days) significantly reduces RVSP, ameliorates right ventricular hypertrophy, inhibits pulmonary vascular remodeling, and increases survival rate to 60% in monocrotaline (HY-N0750)-induced pulmonary hypertension rats via dual inhibition of LOXL2 and stimulation of sGC[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley rat with pulmonary arterial hypertension (male, 160-180 g, hypoxia-induced modeling)[1]
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Dosage:15 mg/kg; 30 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Reduced right ventricular systolic pressure (RVSP) to 37.8 mmHg (vs. hypoxia model 50.8 mmHg) at 15 mg/kg, and to 29.9 mmHg (vs. hypoxia model 50.8 mmHg) at 30 mg/kg, with greater reduction than lenumlostat 30 mg/kg (43.3 mmHg).
Ameliorated right ventricular hypertrophy via decreased RV/(LV + S) ratio and RV/tibia length ratio, without reducing rat body weight.
Reduced total, soluble, and insoluble collagen content in pulmonary arteries, decreased collagen cross-linking (insoluble/soluble collagen ratio), and reduced pulmonary arterial medial wall thickness (PAMT%).
Increased pulmonary artery p-VASP protein levels and decreased PKG1, α-SMA, and collagen I protein levels compared to the hypoxia group.
Chemical Information
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Molecular Weight 544.45
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Formula C23H24F4N4O7
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SMILES
NCC1=CC(C(F)(F)F)=NC(OC2=CC(C(N3C[C@H]([C@@H](C3)F)OC(CCCCO[N+]([O-])=O)=O)=O)=CC=C2)=C1
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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.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Cardiovascular Diseases
Cardiovascular disease can be modeled as maladaptive cardiac remodeling, where ischemic injury or pressure overload activates inflammatory signaling, fibroblast activation, extracellular-matrix deposition, cardiomyocyte hypertrophy, vascular remodeling, and progressive ventricular dysfunction. The TGF-β/SMAD axis is a central profibrotic pathway after myocardial injury and pressure overload, while innate immune and cytokine pathways regulate leukocyte recruitment, scar formation, and adverse remodeling. Key unresolved questions include which inflammatory signals are reparative versus harmful, when fibrosis is protective versus maladaptive, and whether pathway inhibition improves function without weakening necessary infarct healing or compensatory remodeling.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LNO 9 Related Classifications
HY-183644 Related Classifications
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