product name CGI1746
Description: CGI1746 is a potent and highly selective small-molecule inhibitor of the Btk with IC50 of 1.9 nM. CGI-1746 potently inhibits both auto- and transphosphorylation of BTK. It binds to un-phosphorylated BTK and stabilizes it in an inactive enzyme state. In cellular assays, CGI-1746 blocks BCR-mediated B-cell proliferation and suppresses the production of IL-6, IL-1βand TNF in macrophages.
References: Nat Chem Biol. 2011 Jan;7(1):41-50.
579.69
Formula
C34H37N5O4
CAS No.
910232-84-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (172.5 mM)
Water: <1 mg/mL
Ethanol: 33 mg/mL warmed (56.9 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401384
| In Vitro |
In vitro activity: CGI1746 is specific for Btk, with ∼1,000-fold selectivity over Tec and Src family kinases. In an ATP-free competition binding assay, the dissociation constant for Btk is 1.5 nM. CGI1746 inhibits Btk activity in a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 inhibits both auto- and transphosphorylation steps necessary for enzyme activation. CGI1746 completely inhibits anti-IgM–induced murine and human B cell proliferation, with IC50s of 134 nM and 42 nM, respectively, but had no effect on anti-CD3- and anti-CD28–induced T cell proliferation. CGI1746 potently inhibits the proliferation of CD27+IgG+ B cells isolated from the tonsils of four human donors with an average IC50 of 112 nM. In macrophages, CGI1746 abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. CGI1746 potently inhibits TNFα, IL-1β and, to a lesser extent, IL-6 (three- to eight-fold higher IC50) production in human monocytes stimulated with immobilized or soluble immune complexes. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | CGI1746 abrogates B cell–dependent arthritis. CGI1746 treatment (100 mg/kg, s.c, twice-daily dosing) results in significant inhibition (97%) of overall clinical arthritis scores. CGI1746 treatment substantially reduces TNFα, IL-1β and IL-6, as well as MCP1 and MIP-1α on both the mRNA and protein level in the passive anti-collagen II antibody–induced arthritis (CAIA) model. CGI1746 shows comparable efficacy to TNFα blockade and significantly reduces clinical scores, as well as joint inflammation, in mice or rats with established arthritis. |
| Animal model | mouse models |
| Formulation & Dosage | 100 mg/kg; s.c. administration |
| References | Nat Chem Biol. 2011 Jan;7(1):41-50. |
Related Posts
product name CGI1746
Description: CGI1746 is a potent and highly selective small-molecule inhibitor of the Btk with IC50 of 1.9 nM. CGI-1746 potently inhibits both auto- and transphosphorylation of BTK. It binds to un-phosphorylated BTK and stabilizes it in an inactive enzyme state. In cellular assays, CGI-1746 blocks BCR-mediated B-cell proliferation and suppresses the production of IL-6, IL-1βand TNF in macrophages.
References: Nat Chem Biol. 2011 Jan;7(1):41-50.
579.69
Formula
C34H37N5O4
CAS No.
910232-84-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (172.5 mM)
Water: <1 mg/mL
Ethanol: 33 mg/mL warmed (56.9 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401384
| In Vitro |
In vitro activity: CGI1746 is specific for Btk, with ∼1,000-fold selectivity over Tec and Src family kinases. In an ATP-free competition binding assay, the dissociation constant for Btk is 1.5 nM. CGI1746 inhibits Btk activity in a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 inhibits both auto- and transphosphorylation steps necessary for enzyme activation. CGI1746 completely inhibits anti-IgM–induced murine and human B cell proliferation, with IC50s of 134 nM and 42 nM, respectively, but had no effect on anti-CD3- and anti-CD28–induced T cell proliferation. CGI1746 potently inhibits the proliferation of CD27+IgG+ B cells isolated from the tonsils of four human donors with an average IC50 of 112 nM. In macrophages, CGI1746 abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. CGI1746 potently inhibits TNFα, IL-1β and, to a lesser extent, IL-6 (three- to eight-fold higher IC50) production in human monocytes stimulated with immobilized or soluble immune complexes. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | CGI1746 abrogates B cell–dependent arthritis. CGI1746 treatment (100 mg/kg, s.c, twice-daily dosing) results in significant inhibition (97%) of overall clinical arthritis scores. CGI1746 treatment substantially reduces TNFα, IL-1β and IL-6, as well as MCP1 and MIP-1α on both the mRNA and protein level in the passive anti-collagen II antibody–induced arthritis (CAIA) model. CGI1746 shows comparable efficacy to TNFα blockade and significantly reduces clinical scores, as well as joint inflammation, in mice or rats with established arthritis. |
| Animal model | mouse models |
| Formulation & Dosage | 100 mg/kg; s.c. administration |
| References | Nat Chem Biol. 2011 Jan;7(1):41-50. |