1. Cytoskeleton
  2. Lysyl Oxidase
  3. 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.

LNO 9

LNO 9 Chemical Structure

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Description

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[1].

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.

Cell Proliferation Assay[1]

Cell Line: Hypoxia-induced human pulmonary arterial smooth muscle cells (HPASMCs)
Concentration: 20-40 μM
Incubation Time: 24 h
Result: Significantly suppressed hypoxia-induced HPASMC proliferation, with efficacy superior to lenumlostat at equivalent concentrations.

Cell Migration Assay [1]

Cell Line: Hypoxia-induced human pulmonary arterial smooth muscle cells (HPASMCs)
Concentration: 20-40 μM
Incubation Time: 24 h
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.; once daily; for 14 consecutive days) can significantly reduce RVSP in hypoxia-induced pulmonary arterial hypertension rats through dual inhibition of LOXL2 and stimulation of sGC, while ameliorating right ventricular hypertrophy and inhibiting pulmonary vascular remodeling[1].
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.

Animal Model: Sprague-Dawley rat with pulmonary arterial hypertension (male, 160-180 g, hypoxia-induced modeling)[1]
Dosage: 15 mg/kg; 30 mg/kg
Administration: p.o.; daily; 14 days
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.
Molecular Weight

544.45

Formula

C23H24F4N4O7

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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LNO 9
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HY-183644
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