CIDD-8633 is a potent inhibitor of DDR2 with an IC50 of 6.105 μM. It significantly suppresses the proliferation of MIA-PaCa-2 and AsPC-1 cells, with IC25 values of 4.0 and 5.5 μM, respectively. Additionally, CIDD-8633 hinders cell migration, arrests the cell cycle, induces apoptosis (apoptosis), and substantially reduces the growth of pancreatic ductal adenocarcinoma (PDAC) tumors. This compound is applicable in pancreatic cancer research, including studies on PDAC.

DDR2:6.105 μM

CIDD-8633 enhances the stability of DDR2 protein in AsPC-1, MIA PaCa-2, and KPC cells at a temperature range of 40°C-64°C. It inhibits the long-term clonogenic capacity of AsPC1 and MIA-PaCa-2 cells at a concentration of 4-5.5 μM over 7-10 days. CIDD-8633, at 4-6 μM for 72 hours, significantly reduces phosphorylated DDR2 and downstream effector phosphorylated ERK levels in AsPC1 and MIA-PaCa-2 cells. At 1.5 μM over 48 hours, it suppresses nuclear translocation of the DDR2-ERK signaling pathway and blocks proliferation signals in AsPC1 and MIA-PaCa-2 cells. When used in concentrations of 0.1-10 μM for 72 hours, CIDD-8633 decreases pancreatic ductal adenocarcinoma (PDAC) cell proliferation in a dose-dependent manner. At 4 μM for 16 hours, it reduces MIA PaCa-2 cell migration by inhibiting DDR2. Cell cycle progression is inhibited at the G1/S phase in AsPC1 and MIA-PaCa-2 cells at 4-6 μM over 72 hours. The compound also induces apoptosis in these cells through caspase-3 activation. Additionally, CIDD-8633 at 6 μM for 48 hours upregulates genes such as CDKN1A, DDIT3, IL-1β, PMAIP1, and CASP4 in AsPC1 and MIA-PaCa-2 cells. At concentrations of 4-10 μM over 72 hours, it significantly decreases levels of p-DDR2 and p-ERK in AsPC1 and MIA-PaCa-2 cells.

CIDD-8633 (40 mg/kg, i.p., administered twice weekly for 28 days) exerts antitumor effects by targeting DDR2 in mouse models induced with MIA PaCa-2 and Pan02 cells.