product name Tanzisertib(CC-930)
Description: Tanzisertib (CC-930) is a potent JNK1/JNK2/JNK3 inhibitor used for the treatment of fibrotic and infammatory indications. CC-930 is kinetically competitive with ATP in the JNK-dependent phosphorylation of the protein substrate c-Jun and potent against all isoforms of JNK (Ki(JNK1) = 44 ± 3 nM, IC50(JNK1) = 61 nM, Ki(JNK2) = 6.2 ± 0.6 nM, IC50(JNK2) = 5 nM, IC50(JNK3) = 5 nM) and selective against MAP kinases ERK1 and p38a with IC50 of 0.48 and 3.4 μM respectively.
References: Bioorg Med Chem Lett. 2012;22(3):1433-8; J Hepatol. 2014 Dec;61(6):1376-84; Ann Rheum Dis. 2012;71(5):737-45.
484.9
Formula
C21H23F3N6O2.HCl
CAS No.
899805-25-5 (free base)
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 89 mg/mL (183.5 mM)
Water: <1 mg/mL
Ethanol: 89 mg/mL (183.5 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: CC-930 inhibits the formation of phospho-cJun in human PBMC stimulated by phorbol-12-myristate-13-acetate and phytohemeagglutinin (IC50=1 μM). CC-930 (1-2 μM) substantially reduces hepatocyte apoptosis and necrosis, abrogates apoptosis and necrosis in FC-loaded WT hepatocytes. CC-930 blocks the JNK pathway that is activated by pro-fibrotic cytokines in systemic sclerosis. Kinase Assay: Cell Assay: Systemic sclerosis (SSc) fibroblasts are incubated with 1 µM CC-930 in 96-well plates for 20 h. Then MTT is added at a final concentration of 1 mg/mL, and the cells are further incubated at 37°C for 4 h. Mock-treated fibroblasts are used as controls, and all other results are normalised to untreated cells. |
|---|---|
| In Vivo | In the acute rat LPS-induced TNFα production PK-PD model, the compound inhibits the production of TNFα by 23% and 77% at 10 and 30 mg/kg oral dose respectively. CC-930 is well-tolerated and exposure is dose-proportional. |
| Animal model | Male C57Bl/6 mice |
| Formulation & Dosage | Dissolved in 5% DMA and 30% PEG 400 (i.v.) or 0.5% CMC/0.25% Tween80(p.o.); 2 mg/kg(i.v.) or 10 mg/kg(p.o.); i.v. or p.o. |
| References | Bioorg Med Chem Lett. 2012;22(3):1433-8; J Hepatol. 2014 Dec;61(6):1376-84; Ann Rheum Dis. 2012;71(5):737-45. |
