Tanzisertib is a potent, selective, and orally active c-Jun amino-terminal kinase (JNK) inhibitor used for treatment of dermal fibrosis.
Tanzisertib (CC-930, JNK-930, JNKI-1) has an ATP-competitive inhibitory effect on the phosphorylation of the JNK-dependent protein substrate c-Jun and 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), selective inhibition of ERK1 and p38a with IC50 of 0.48 μM and 3.4 μM, respectively .
In the acute PK-PD rat model of LPS-induced TNFα production, oral administration of 10 mg/kg and 30 mg/kg of CC-930 reduced the production of TNFα in vivo by 23% and 77%, respectively. CC-930 is well tolerated in vivo and its effect is proportional to dose.
| Target | Value |
JNK3
(Cell-free assay) | 0.006 μM |
JNK2
(Cell-free assay) | 0.007 μM |
< td style="border-bottom: 1px dotted #ccc;padding: 5px;"> JNK1
(Cell-free assay) 0.061 μM |
JNK3: 6 nM (IC50); JNK2: 7 nM (IC50); JNK1: 61 nM (IC50)
