Tie-2

Razuprotafib (AKB-9778) is a protein tyrosine phosphatase ß (HPTPß) inhibitor with an IC50 of 50 nM. It effectively activates Tie-2 and provides protection against acute kidney injury.

Regorafenib (BAY 73-4506) is an orally active, multi-targeted receptor tyrosine kinase inhibitor that inhibits RET, C-RAF, VEGFR2, c-Kit, VEGFR1, and PDGFRβ, exhibiting both antitumor and anti-angiogenic activity.

CEP-11981 is an orally active TIE2 pan-VEGFR inhibitor with broad tyrosine kinase inhibitory activity, exhibiting antitumour and anti-angiogenic effects, and is applicable for the treatment of refractory solid tumours.

CE-245677 is a potent, reversible inhibitor of Tie2 and TrkA B kinases, with cellular IC50 values of 4.7 nM and 1 nM, respectively.

GSK-1070916 (GSK-1070916A) is a reversible and ATP-competitive inhibitor of Aurora B C with IC50 of 3.5 nM 6.5 nM. It displays >100-fold selectivity against the closely related Aurora A-TPX2 complex. Phase 1.

EOC317 (ACTB-1003) is an oral kinase inhibitor with IC50 values of 6 nM, 2 nM, and 4 nM for FGFR1, VEGFR2, and Tie-2, respectively.

Foretinib (GSK1363089) is a broad-spectrum tyrosine kinase inhibitor with IC50s of 0.4 nM and 0.9 nM for Met and KDR.

Pexmetinib (ARRY-614) is an orally bioavailable dual p38 MAPK Tie-2 inhibitor studied in acute myeloid leukemia and inhibits osteoclastogenesis and breast cancer-induced osteolysis via the P38 STAT3 signaling pathway.

Vanucizumab is a bispecific humanised monoclonal antibody that simultaneously inhibits the receptor interactions of VEGF-A and Angiopoietin-2 (Ang-2), exhibiting anti-angiogenic and anti-cancer effects, and can be used for the treatment of advanced solid tumours.

Altiratinib (DCC-2701)(DCC-2701) is a novel c-MET/TIE-2/VEGFR inhibitor; effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with an HGF antagonist in vitro.

Regorafenib Monohydrate is a novel oral multikinase inhibitor with IC50 values of 13, 4.2, 46, 22, 7, 1.5, 2.5, 28, 19 nM for VEGFR1, murine VEGFR2, murine VEGFR3, PDGFR-β, KIT, RET, RAF-1, B-RAF and B-RAF(V600E) respectively.

Cpd27 (TIE-2 VEGFR-2 kinase-IN-2) is a TIE-2 and VEGFR-2 inhibitor that inhibits RIPK1 and protects RGCs from TNF-stimulated cell death and can be used to study glaucoma.

NVP-BAW2881 (BAW2881) is a potent and selective VEGFR (vascular endothelial growth factor receptor tyrosine kinase) inhibitor with efficacy in inhibiting chronic and acute skin inflammation.

BAY-826 is a novel, potent and selective TIE-2 inhibitor that inhibits TIE-2 phosphorylation and can be used to study tumors.

Tie2 kinase inhibitor 1 (Tie2 kinase inhibitor), an optimized compound of SB-203580, is selective to Tie2 with IC50 of 0.25 μM, which is 200-fold more effective than p38.

TIE-2 VEGFR-2 kinase-IN-5 (TIE-2 and VEGFR-2 tyrosine kinase receptor inhibitor) is a potent agent with anti-angiogenic activity, commonly used in biomedical research focused on angiogenesis.

CE-245677 mesylate is a selective Tie2 kinase inhibitor with oral activity and potential antitumor effects, used for pain research.

Zansecimab (LY-3127804) is a monoclonal antibody targeting angiopoietin 2 (Ang 2) for the study of cardiovascular and immune diseases.

5α-Hydroxycostic acid, a naturally occurring sesquiterpene, inhibits choroidal neovascularization in rats through dual signaling pathways mediated by VEGF VEGFR and Ang2 Tie2 (angiopoietin 2), and exhibits anti-inflammatory and anti-angiogenic effects on human breast cancer cells

GW768505A free base is a potent dual inhibitor of VEGFR2 (KDR) and Tie-2 (pIC50: 7.81 for VEGFR2) with anti-angiogenic activity.

TIE-2 VEGFR-2 kinase-IN-4, a benzimidazole derivative, is a potent inhibitor of the tyrosine kinase receptors TIE-2 and VEGFR-2, with IC50 values of 5.2 nM and 5.1 nM, respectively. This compound is utilized in angiogenesis research [1].

Regorafenib (BAY 73-4506) mesylate is an orally active multi-target receptor tyrosine kinase inhibitor, inhibiting VEGFR1 2 3 (IC50=13 4.2 46 nM), PDGFRβ (IC50: 22 nM), Kit (IC50: 7 nM), RET (IC50: 1.5 nM), and Raf-1 (IC50: 2.5 nM), with potent anti-tumor and anti-angiogenic effects.

CEP-14083 is a potent ALK inhibitor that has shown activity in an NPM ALK–carrying T-cell lymphoma in vitro study. Presumably, this compound binds to the hinge region of the kinase in an ATP-competitive manner. CEP-14083 displays a potent activity against ALK in enzymatic assays (IC50 = 11 nmol L). Further, CEP-14083 is also able to inhibit the insulin receptor at a concentration within a nanomolar range. In a preclinical assay, CEP-14083 showed that, via NPM ALK TK inhibition, it could control the expression of molecules that determine T-cell identity and signaling in lymphoma cells. CEP-14083 has shown preclinical activity in both cell lines and animal models harboring ALK alteration.

2-MT 63 is a novel TIE-2 kinase inhibitor that demonstrates unique and improved kinase selectivity compared to other inhibitors known to interact with TIE-2. 2-MT 63 has a good kinase selectivity profile in enzyme assays with >30-fold selectivity (typically much greater) against the tested kinases. Importantly, the profile includes selectivity against other targets of relevance for angiogenesis (KDR, PDGFR, EPHB4).