DDR1 Inhibitor

Sitravatinib (MGCD516) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC₅₀s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively. Sitravatinib shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.

GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC₅₀ values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.

VU6015929 is a potent, selective and orally active dual discoidin domain receptor 1/2 (DDR1/2) inhibitor with IC₅₀s of 4.67 nM and 7.39 nM, respectively. VU6015929 potently blocks collagen-induced DDR1 activation and collagen-IV production.

DDR1-IN-4 (Compound 2.45) is a selective and potent Discoidin Domain Receptor 1 (DDR1) autophosphorylation inhibitor, with IC₅₀ values of 29 nM and 1.9 μM for DDR1 and DDR2, respectively.

AP4-43 is an orally active CLK1, CLK4, PI3K, DDR1, EGFR and NEK4 inhibitor. AP4-43 reduces growth of mammalian colorectal cancer organoids. AP4-43 improves survival in a transgenic Drosophila model of KRAS-mutant colorectal cancer. AP4-43 can be used for the research of KRAS-mutant colorectal cancer.

DDR1-IN-6 is a selective Discoidin Domain Receptor family, member 1 (DDR1) inhibitor with an IC₅₀ of 9.72 nM. DDR1-IN-6 inhibits auto-phosphorylation DDR1b (Y513) with an IC₅₀ of 9.7 nM. DDR1-IN-6 has anti-cancer activity. DDR1-IN-6 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

DDR1/2 inhibitor-2 (Example 31) is a DDR1/DDR2 inhibitor, with IC₅₀ values less than 100 nM. DDR1/2 inhibitor-2 can be used for research of cancer and fibrotic diseases.

DDR1-IN-5 is a selective Discoidin Domain Receptor family, member 1 (DDR1) inhibitor with an IC₅₀ of 7.36 nM. DDR1-IN-5 inhibits auto-phosphorylation DDR1b (Y513) with an IC₅₀ of 4.1 nM. DDR1-IN-5 has anti-cancer activity. DDR1-IN-5 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

DDR1-IN-1 dihydrochloride is a potent and selective DDR1 receptor tyrosine kinase inhibitor with an IC₅₀ of 105 nM; 4-fold less potent for DDR2 (IC₅₀ = 413 nM).

SR-302, a chemical probe, is a potent and selectivity DDR/p38 inhibitor, with IC₅₀ values of 0.125, 0.023 and 0.018 μM for p38α, DDR1 and DDR2, respectively. SR-302 can be used for the research of fibrotic disorders, such as renal and pulmonary fibrosis, atherosclerosis, and various forms of cancer.

Sitravatinib malate (MGCD516 malate) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC₅₀s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively. Sitravatinib malate shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.

Axl-IN-21 is an orally active and selective AXL inhibitor (K_d = 2.7 nM, IC₅₀ = 4.0 nM). Axl-IN-21 displays kinase selectivity and retains strong activity against cancer-related mul-kinases (Mer with K_d = 1.4 nM, DDR1 with IC₅₀ = 22.2 nM, HIPK4 with K_d = 11.0 nM and LOK with K_d =10 nM). Axl-IN-21 overcomes tumor microenvironment-driven resistance by blocking CAF-derived GAS6-induced AXL/STAT3/ABCG1 signaling, restoring chemosensitivity and inhibiting drug efflux in gastric cancer (GC). Axl-IN-21 suppresses TGF-β1-induced epithelial-mesenchymal transition (EMT), migration, and invasion in MDA-MB-231 cells. Axl-IN-21 exhibits no significant cytotoxicity in non-cancerous cells. Axl-IN-21 can be research for triple negative breast cancer and gastric cancer^{[1] [2]} .

DDR1/2 IN-4 (Compound 37) is a selective dual DDR1 and DDR2 kinase inhibitor, with a pK_i of 8.6 for DDR1 and a pK_i of 8.2 for DDR2. DDR1/2 IN-4 functionally inhibits the kinase activities of DDR1 and DDR2. DDR1/2 IN-4 inhibits the release of MCP-1. DDR1/2 IN-4 can be used in studies related to idiopathic pulmonary fibrosis.

DDR1-IN-11 (Compound 4) is an inhibitor of Discoidin domain receptor 1 (DDR1) with an IC₅₀ of 46.16 nM. DDR1-IN-11 can achieve an inhibition rate of 99.86% against Z-138 cells at a concentration of 10 μM, and it can be used in the research of acute myeloid leukemia (AML).

DDR1-IN-8 (compound 7s) is a potent inhibitor of DDR1/2, with the IC₅₀ values of 0.045 μM and 0.126 μM, respectively. DDR1-IN-8 has anti-tumor activity.

DDR1/2 inhibitor-3 (5n) is a DDR1/2 inhibitor, with IC₅₀ values​of 9.4 and 20.4 nM, respectively. DDR1/2 inhibitor-3 can be used in anti-inflammatory research.