TAM Receptor Inhibitor

Bemcentinib (R428) is a selective and orally active Axl inhibitor with an IC₅₀ of 14 nM. Bemcentinib retards cancer cell migration and invasion. Bemcentinib exhibits >100-fold selectivity for Axl versus Abl and 50- and >100-fold selectivity over TAM family kinases Mer and Tyro3, respectively, in cells. Bemcentinib blocks tumor spread and prolongs survival in models of metastatic breast cancer.

Cabozantinib is a potent and orally active inhibitor of VEGFR2 and MET, with IC₅₀ values of 0.035, and 1.3 nM, respectively. Cabozantinib displays strong inhibition of KIT, RET, AXL, TIE2, and FLT3 (IC₅₀=4.6, 5.2, 7, 14.3, and 11.3 nM, respectively). Cabozantinib shows antiangiogenic activity. Cabozantinib disrupts tumor vasculature and promotes tumor and endothelial cell apoptosis.

Gilteritinib (ASP2215) is a potent and ATP-competitive FLT3/AXL inhibitor with IC₅₀s of 0.29 nM/0.73 nM, respectively.

2-D08 is a cell permeable, mechanistically unique inhibitor of protein SUMOylation. 2-D08 also inhibits Axl with an IC₅₀ of 0.49 nM.

BMS 777607 (BMS 817378) is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC₅₀s of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM, respectively, and 40-fold more selective for Met-related targets than Lck, VEGFR-2, and TrkA/B, with more than 500-fold greater selectivity versus all other receptor and non receptor kinases.

Ladarutatug is a humanized monoclonal antibody targeting Tyrosine-protein kinase receptor UFO. The Ladarutatug antibody isotype is human IgG4κ; the recommended isotype control is Human IgG4 (S228P) kappa, Isotype Control (HY-P99003).

TAM-IN-1 (compound 1) is a potent macrocyclic inhibitor of Axl and Mer, with K_is of 130 pM and <50 pM, respectively.

UNC2250 is a potent and selective Mer inhibitor with an IC₅₀ of 1.7 nM, about 160- and 60-fold selectivity over the closely related kinases Axl/Tyro3.

Zanzalintinib (XL092) is an orally active, ATP-competitive inhibitor of multiple receptor tyrosine kinases (RTKs) including MET, VEGFR2, AXL and MER, with IC₅₀s in cell-based assays of 15 nM, 1.6 nM, 3.4 nM, 7.2 nM respectively. Zanzalintinib exhibits anti-tumor activity. Zanzalintinib has the potential for kinase-dependent diseases and conditions research.

Dubermatinib (TP-0903) is a potent and selective Axl receptor tyrosine kinase inhibitor with an IC₅₀ value of 27 nM.

LDC1267 is a AXL/TAM/FLT3 inhibitor with IC₅₀ values of 42 nM, 130 nM, and 63 nM against AXL, MERTK, and TYRO3, respectively. LDC1267 blocks GAS6-induced AXL phosphorylation and the downstream AKT/ERK1/2 signaling pathway. LDC1267 inhibits cancer cell proliferation, colony formation, and glioblastoma cell invasion, without causing obvious impairment of cytotoxic autophagic flux. LDC1267 exerts a synergistic effect when used in combination with Imatinib (HY-15463) in chronic myeloid leukemia models. LDC1267 can be widely applied in studies related to glioblastoma and chronic myeloid leukemia.

UNC569 is a potent, reversible, ATP-competitive and orally active Mer kinase inhibitor with an IC₅₀ of 2.9 nM and a K_i of 4.3 nM. UNC569 also inhibits Axl and Tyro3 with IC₅₀s of 37 nM and 48 nM, respectively. UNC569 can be used for acute lymphoblastic leukemia (ALL) and atypical teratoid/rhabdoid tumors research

UNC5293 is a MERTK-selective and potent inhibitor (K_i=190 pM). UNC5293 inhibits MERTK (IC₅₀=0.9 nM) and is more selective over Axl, Tyro3 and Flt3. UNC5293 exhibits excellent mouse PK properties and is used for bone marrow leukemia research.

Gilteritinib (ASP2215) hemifumarate is a potent and ATP-competitive FLT3/AXL inhibitor with IC₅₀ of 0.29 nM/0.73 nM, respectively.

UNC2541 is a potent and Mer tyrosine kinase (MerTK)-specific inhibitor, binds in the MerTK ATP pocket, with an IC₅₀ of 4.4 nM, more selective over Axl, Tyro3 and Flt3. UNC2541 inhibits phosphorylated MerTK (pMerTK; EC₅₀, 510 nM). UNC2541 abolishes the analgesic and anti-inflammatory effects of ozone in vivo and in vitro.

Tamnorzatinib (ONO-7475) is a potent, selective, and orally active Axl/Mer inhibitor with IC50 values of 0.7 nM and 1.0 nM, respectively. Tamnorzatinib sensitizes AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs, suppresses the emergence and maintenance of tolerant cells. Tamnorzatinib combines with Osimertinib (HY-15772) provides a bright promise for the study of EGFR-mutated non-small cell lung cancer (NSCLC).

CEP-40783 is a potent, selective and orally available inhibitor of AXL and c-Met with IC₅₀ values of 7 nM and 12 nM, respectively.

RU-301 is a pan TAM inhibitor that blocks Gas6-induced TAM activation and tumorigenicity. RU-301 significantly reduces nonalcoholic steatohepatitis (NASH) fibrosis, along with attenuates ERK activation and TGFβ1 expression. RU-301 can be used in studies of cancer and nonalcoholic steatohepatitis.

SGI-7079 is a selective, ATP-competitive, orally active inhibitor of the receptor tyrosine kinase Axl. SGI-7079 blocks Axl-mediated signaling pathways such as NF-κB activation and MMP-9 expression, thereby inhibiting tumor cell proliferation, migration and invasion. SGI-7079 is mainly used in the research of malignant tumors such as inflammatory breast cancer and bladder cancer, as well as in combination with immunization (used in combination with PD-1 therapy)[1][2][3].

Tilvestamab (BGB149) is a humanized anti-AXL antibody that blocks AXL-mediated cell signaling. Tilvestamab significantly inhibits Gas6-induced AXL activation in 786-0-Luc RCC cells and inhibits downstream AKT phosphorylation. Tilvestamab can be used in cancer research, particularly in AXL overexpressing renal cell carcinomas.