product name Laquinimod
Description: Laquinimod (also known as ABR-215062, LAQ) is an orally active immunoregulator. Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the CNS that can be elicited in rodents and represents the major animal model for the study of multiple sclerosis (MS). Laquinimod treatment at 0.1-1 μM does not affect the viability of peripheral blood mononuclear cells (PBMC). By performing the large-scale gene expression microarray analysis in PBMC from healthy subjects or relapsing-remitting multiple sclerosis (RRMS) patients, Laquinimod is shown to induce suppression of genes related to antigen presentation and corresponding inflammatory pathways.
References: Neuropharmacology. 2002 Apr;42(5):731-9; J Neuroimmunol. 2002 Sep;130(1-2):163-72; J Neuroimmunol. 2010 Apr 15;221(1-2):87-94.
356.8
Formula
C19H17ClN2O3
CAS No.
248281-84-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 61 mg/mL (170.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
ABR-215062, LAQ
other peoduct :
| In Vitro |
In vitro activity: Laquinimod treatment at 0.1-1 μM does not affect the viability of peripheral blood mononuclear cells (PBMC). By performing the large-scale gene expression microarray analysis in PBMC from healthy subjects or relapsing-remitting multiple sclerosis (RRMS) patients, Laquinimod is shown to induce suppression of genes related to antigen presentation and corresponding inflammatory pathways. Laquinimod induces activation of Th2 response in CD14+ and CD4+ cells and suppression of proliferation in CD8+ cells. Laquinimod displays significant effects on immune modulation related to the suppression of antigen presenting mechanism followed by a decrease of chemotaxis and adhesion, and exhibits potent anti-inflammatory potency through the suppression of the NF-κB pathway that concordantly leads to the activation of apoptosis of immuno-competent cells. Kinase Assay: Cell Assay: The peripheral blood mononuclear cells (PBMC) are incubated with Laquinimod for 24 hours. Cell viability is measured on total PBMC by propidium iodide (PI) staining using an automated cell counter. Protein expression level is assessed in PBMC samples by Western blot using anti-HLA-DQA/DQB monoclonal antibodies. |
|---|---|
| In Vivo | Administration of Laquinimod (0.16-16 mg/kg/day) dose-dependently inhibits the incidence of experimental autoimmune neuritis (EAN) in Lewis rats, ameliorates clinical signs and inhibits P0 peptide 180-199-specific T cell responses as well as the inflammation and demyelination in the peripheral nerves, suggesting that Laquinimod may mediate its effects by regulation of Th1/Th2 cytokine balance. Laquinimod significantly inhibits the development of murine acute experimental autoimmune encephalomyelitis (EAE), being approximately 20 times more potent than the immunomodulator roquinimex. Laquinimod treatment inhibits the development of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat in a dose-dependent manner, and shows better disease inhibitory effects as compared to roquinimex (Linomide). Laquinimod potently inhibits the development of chronic experimental autoimmune encephalomyelitis (chEAE) in IFN-beta k.o. mice and wild type mice. Laquinimod reduces clinical signs, inflammation, and demyelination in C57BL/6 mice with active EAE induced with MOG(35-55) peptide, and down-regulates VLA-4-mediated adhesiveness and pro-inflammatory cytokines such as IL-17. The study of Laquinimod in the mice model of EAE using a conditional BDNF knockout strain lacking BDNF expression in myeloid cells and T cells (LLF mice) indicates Laquinimod also modulates autoimmune demyelination via induction of brain-derived neurotrophic factor (BDNF). |
| Animal model | Lewis rats with experimental autoimmune neuritis (EAN) induced by inoculation with peripheral nerve myelin P0 protein peptide 180-199 and Freunds complete adjuvant |
| Formulation & Dosage | Dissolved in PBS; 0.16, 1.6 and 16 mg/kg/day; s.c. daily |
| References | Neuropharmacology. 2002 Apr;42(5):731-9; J Neuroimmunol. 2002 Sep;130(1-2):163-72; J Neuroimmunol. 2010 Apr 15;221(1-2):87-94. |
