LCB 03-0110 is a potent, ATP-competitive inhibitor of Discoidin domain receptor (DDR) family and c-Src tyrosine kinase family, as well as Btk and Syk; potently inhibits the activated tyrosine kinase activity of DDR2 (IC50=6 nM), and nonactivated form of DDR2 (IC50=145 nM); suppresses collagen-induced autophosphorylation of DDR1 and DDR2 with IC50 of 164 and 171 nM in cell-based assays; inhibits all eight Src family kinases with IC50 of 2-20 nM; suppresses the proliferation and migration of primary dermal fibroblasts induced by TGF β1 and type I collagen (IC50=194 nM), inhibits cell migration and nitric oxide, iNOS, COX2, and TNF-α synthesis in LPS-activated J774A.1 macrophage cells; suppresses hypertrophic scar formation in wound healing models.

Dual DDR1 and DDR2 inhibitor 5n is a highly potent, selective, dual Discoidin domain receptor DDR1 and DDR2 inhibitor with Kd of 7.9 and 8.0 nM, IC50 of 9.4 and 20.4 nM, repectively; displays significant selectivity against a panel of 403 wild-type kinases at 1 uM (Abl1 IC50=494 nM); dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) release in mouse primary peritoneal macrophages (MPMs), attenuates lung pathophysiologic changes in LPS-challenged mice, effectively decreases the levels of TNF-α and IL-6 both in BALF and serum.

DDR2-IN-5 is a potent, dual DDR2/SRC inhibitor with IC50 of 56/12 nM, potently suppresses DDR2 mutated cell lines HCC-366 and NCI-H2286 with IC50 of 0.44 uM and 0.29 uM.

DDR1 inhibitor 7rh is a potent, selective, ATP-competitive, orally available Discoidin domain receptor 1 (DDR1) inhibitor with IC50 of 6.8 nM in cell-free kinase assays; DDR1 inhibitor 7rh is significantly less potent in suppressing the kinase activities of DDR2 (IC50=101 nM), Bcr-Abl (IC50=355 nM), and c-Kit (IC50>10 uM); inhibits DDR1-mediated signaling induced by soluble collagen (50 μg/ml) in a concentration-dependent manner, inhibits activation of PYK2 and PEAK1, signaling proteins downstream of DDR1 in PANC-1 cells; induces significant decrease of total protein levels of DDR1 and Bcl-xL, causes a significant reduction in the level of MMP-2 in NSCLS cells; suppresses the growth of K562 human CML cells with IC50 of 38 nM, A549, NCI-H23 and NCI-H460 human NSCLC cells with IC50 of 2.7, 2.1 and 3.0 µM, respectively; abrogates collagen-induced DDR1 signaling in pancreatic tumor cells and consequently reduces colony formation and migration, exhibits striking efficacy in combination with chemotherapy in orthotopic xenografts and autochthonous pancreatic tumors.

DDR1 inhibitor 2.45 (Compound 2.45) is a novel potent, selective, bioavailable Discoidin Domain Receptor 1 (DDR1) inhibitor with IC50 of 29 nM, displays 64-fold selectivity over DDR2 in biochemical assays; also possesses excellent kinome selectivity against a kinase panel of 468 kinases; Compound 2.45 inhibits DDR1 phosphorylation (70% inhibition at 1 uM in HT1080 cells overexpressing DDR1) and recruitment of SHC1 in vitro, and modulates phenotype of collagen stimulated renal epithelial cells; Compound 2.45 preserves renal function and reduces tissue damage in Col4a3−/− mice (the preclinical mouse model of Alport syndrome).

DDR-TRK-1 (DDR1 inhibitor 6j) is a potent, selective selective DDR1 inhibitor with IC50 of 9.4 nM, also potently inhibits TRK family with IC50 of 18-100 nM; DDR-TRK-1 inhibits colony formation and migration of Panc-1 pancreatic cancer cells. In cellular and mouse models of lung fibrosis, DDR-TRK-1 inhibits signaling, expression of fibrotic markers and fibrotic features such as hydroxproline expression; DDR-TRK-1 is selective in KINOMEscan at 1 uM,t he closest off target is CDK11 (370 nM).

DDR inhibitor X is a potent discoidin domain receptor (DDR) inhibitor with IC50 of 3.3 nM for DDR2, and shows 53% inhibition on DDR1 at 1.5 nM.

ALW-II-49-7 (DDR2-IN-1) is a potent, selective DDR2 inhibitor with IC50 of 18.6 nM, also shows ability to inhibit DDR1 and Ephrin-family kinases (IC50=40 nM for EphB2); displays excellent overall kinase selectivity against a panel of over 350 kinases; decreases DDR2 phosphorylation but has little effect on the proliferation of DDR2 mutated cancer cell lines.

WRG-28 (DDR2 inhibitor WRG-28) is a potent, selective, allosteric inhibitor of discoidin domain receptor 2 (DDR2) with binding IC50 of 230 nM; blunted collagen I-mediated DDR2 tyrosine phosphorylation, ERK activation, and SNAIL1 protein stabilization (IC50=286 nM) in HEK293 cells expressing DDR2, without effect on normal mammary epithelial MCF10A cells; displays no activity against collagen I-induced tyrosine phosphorylation of the related DDR1 RTK in HEK293 cells; WRG-28 inhibits DDR2-collagen interaction in an allosteric manner, inhibits tumor invasion and migration, as well as tumor-supporting roles of the stroma, and inhibits metastatic breast tumor cell colonization in the lungs.

LCB 03-0110 is a potent, ATP-competitive inhibitor of Discoidin domain receptor (DDR) family and c-Src tyrosine kinase family, as well as Btk and Syk; potently inhibits the activated tyrosine kinase activity of DDR2 (IC50=6 nM), and nonactivated form of DDR2 (IC50=145 nM); suppresses collagen-induced autophosphorylation of DDR1 and DDR2 with IC50 of 164 and 171 nM in cell-based assays; inhibits all eight Src family kinases with IC50 of 2-20 nM; suppresses the proliferation and migration of primary dermal fibroblasts induced by TGF β1 and type I collagen (IC50=194 nM), inhibits cell migration and nitric oxide, iNOS, COX2, and TNF-α synthesis in LPS-activated J774A.1 macrophage cells; suppresses hypertrophic scar formation in wound healing models.