TAM Receptor

Bemcentinib (R428) is a selective inhibitor of Axl (IC50: 14 nM) and has been investigated for the treatment of NSCLC.

Gilteritinib (ASP2215) is a potent inhibitor of FMS-related tyrosine kinase 3 (FLT3) and AXL tyrosine kinase receptors (IC50 = 0.29 nM and <1 nM, respectively). In preclinical studies, gilteritinib demonstrated strong antileukemic and antitumor effects. Gilteritinib is currently in several Phase 3 clinical trials for acute myeloid leukemia.

Tepotinib (EMD-1214063) is a c-MET tyrosine kinase inhibitor (IC50=3 nM) that is selective, orally active, and ATP-competitive. Tepotinib has antitumor effect and is used in the treatment of non-small cell lung cancer.

Cabozantinib (XL184) is a multi-targeted tyrosine kinase receptor inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt3 (IC50=0.035 1.3 4.6 7 11.3 nM). Cabozantinib exhibits both antitumor and antiangiogenic activity.

2-D08 is a synthetic flavone that inhibits sumoylation, also inhibits Axl with an IC50 of 0.49 nM.2-D08 showed anti-aggregatory and neuroprotective effect.

UNC2025 (mrx-6313)(IC50 of 0.74 nM and 0.8 nM) is a potent and orally bioavailable dual MER FLT3 inhibitor. UNC-2025 is about 20-fold selectivity higher than Axl and Tyro3.

Pralatrexate (10-Propargyl-10-deazaaminopterin) is a folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities.

Sitravatinib (MGCD516) is an inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Met, c-Kit, PDGFRα β, PDGFR, and Axl.

2-(Chloromethyl)-4-(4-nitrophenyl)thiazole, a natural product derived from Astragalus propinquus, exhibits anticancer activity and has been shown to be effective in hepatocellular carcinoma (HCC) by inhibiting the M2 polarization of tumor-associated macrophages (TAM).

SGI-7079 is a new selective Axl inhibitor. SGI-7079 can be a dose-dependent manner inhibited growth of tumors. It is also a potential therapeutic target for EGFR inhibitor resistance.

NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor (IC50=2.5 µM) with no activity against other dehydrogenases. NCT-503 has antitumor activity and inhibits the growth of PHGDH-dependent tumors.

AXL-IN-13 is a potent and orally active AXL inhibitor with an IC50 of 1.6 nM and a Kd of 0.26 nM. It exhibits anticancer activity, reverses TGF-β1-induced epithelial-mesenchymal transition (EMT), and inhibits cancer cell migration and invasion.

DS-1205 is a potent and selective inhibitor of AXL kinase, with an IC50 of 1.3 nM. DS-1205 also inhibits MER, MET, and TRKA, with IC50s of 63, 104, and 407 nM, respectively. DS-1205 can inhibit cell migration in vitro and tumor growth in vivo[1].

Ningetinib (CT-053) (CT053PTSA) is an orally bioavailable tyrosine kinase inhibitor with IC50s of <1.0, 1.9 and 6.7 nM for Axl, VEGFR2, and c-Met, respectively.

UNC569 (UNC 569) is a selective inhibitor of URAT1, a transporter in the kidney that regulates uric acid excretion from the body. It is also a selective uric acid re-absorption inhibitor. UNC569 could normalize the amount of uric acid excreted by gout patients previously classified as under-excretors.

UNC2025 is a potent and orally bioavailable Mer/Flt3 dual inhibitor with IC50 of 0.8/0.74 nM for Mer/Flt3.

Gilteritinib hemifumarate (ASP2215 hemifumarate) is a potent ATP-competitive dual FLT3 (IC50: 0.29 nM) and AXL (IC50: 0.73 nM) inhibitor for the treatment of relapsed or refractory FLT3 mutant AML.

Dubermatinib (TP0903) is a potent and selective Axl kinase inhibitor.

S49076 is a novel and potent inhibitor of MET, AXL MER, and FGFR1 2 3, effectively blocking cellular phosphorylation of MET, AXL, and FGFRs.

BMS 777607 (BMS 817378) is a Met-related inhibitor targeting c-Met, Axl, Ron, and Tyro3 with IC50 values of 3.9 nM, 1.1 nM, 1.8 nM, and 4.3 nM, respectively. BMS-777607 has been investigated in basic science research for malignant solid tumors.

Emactuzumab(RG 7155) is a monoclonal antibody against colony-stimulating factor-1 receptor targeting tumor-associated macrophages (TAMs) Emactuzumab has antitumor activity and inhibits activation of colony-stimulating factor 1 receptor (CSF1R) Emactuzumab has a high affinity for CSF-1R with a Ki value of 0.2 nM. Emactuzumab blocks CSF-1R dimerization and can be used to study cancers such as diffuse tenosynovial giant cell tumor (dt-GCT).

Cabozantinib S-malate (XL184) is the s-malate salt form of cabozantinib, an orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity.

UNC2250 is an effective and specific Mer inhibitor (IC50=1.7 nM).

G-749, a new-type FLT3 inhibitor, exhibits effective and sustained inhibition of the FLT3 wild type and mutants.

ONO-7475 is an inhibitor with high specificity for anexelekto and MER tyrosine kinase

Cabozantinib hydrochloride (XL184) is a potent pan-tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt4 (IC50s: 0.035, 1.3, 4.6, 7 and 6 nM).

LDC1267 is a excellently specific TAM(Tyro3, Axl and Mer) kinase inhibitor, for Mer( IC50<5 nM), Tyro3(IC50=8 nM), and Axl(IC50=29 nM).

Merestinib dihydrochloride (LY2801653 dihydrochloride) is an orally available kinase inhibitor with antitumor activity that inhibits MET, AXL, RON, and MKNK1 2, and inhibits the growth of NTRK fusion-carrying tumors.

UNC2541 is a potent and specific inhibitor of Mer tyrosine kinase (MerTK), binding in the MerTK ATP pocket (IC50: 4.4 nM) and inhibiting phosphorylated MerTK (pMerTK) with an EC50 of 510 nM.

XL092 (JUN04542) is an Axl Mer cMet KDR inhibitor for the treatment of Axl and Mer receptor tyrosine kinase- dependent disorders.

NPS-1034 is a dual Met Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively.

TAM-IN-2 is an inhibitor of TAM.

UNC 569 hydrochloride is a reversible and ATP-competitive inhibitor of Mer with an IC50 of 2.9 nM and a Ki of 4.3 nM. UNC 569 hydrochloride inhibits Axl and Tyro3 with IC50s of 37 nM and 48 nM, respectively. UNC 569 hydrochloride can be used in studies about acute lymphoblastic leukemia and atypical teratoid/rhabdoid tumors.

RU-302 is a pan inhibitor of TAM Receptor blocking the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. RU-302 effectively blocks the activation of Gas6-inducible AXL and suppresses lung cancer tumor growth.

UNC2881 is a specific Mer tyrosine kinase inhibitor (IC50: 4.3 nM). It is about 83- and 58-fold higher selectivity than Axl and Tyro3, respectively.

Ningetinib Tosylate is an orally bioavailable tyrosine kinase inhibitor with IC50s of <1.0, 1.9 and 6.7 nM for Axl, VEGFR2, and c-Met, respectively.

CEP-40783 (RXDX-106) is an effective, specific and orally active AXL c-Met inhibitor (IC50: 7 12 nM). It also inhibits MER and TYRO3 (IC50: 29 19 nM).

BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3.

RU-301 is a novel pan-tam inhibitor

Axl-IN-16, a dual Axl/HIF inhibitor, promotes Flammulina velutipes fruiting body formation and suppresses hypoxia-inducible factor activity along with receptor tyrosine kinase expression [1].

AXL-IN-15 (cpd391) is a potent Axl inhibitor with a dissociation constant (K i) and half-maximal inhibitory concentration (IC50) of less than 1 nanomolar (nM), suitable for cancer research [1].

Sitravatinib malate is an orally bioavailable receptor inhibitor of tyrosine kinase (RTK) (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.) , shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.

Enapotamab is an AXL UFO-related antibody that can be used to synthesize antibody-drug couplings (Enapotamab Vedotin).

Mecbotamab vedotin (BA301) is an inhibitory IgG1 antibody that targets human tyrosine kinase receptor AXL and the humanized murine monoclonal BA301 γ1 chain. It can be utilized in the preparation of immunoconjugates for research into cancers expressing the Axl type.

S49076 HCl (S-49076 Hydrochloride) is an effective inhibitor of MET, AXL/MER, and FGFR1/2/3. S49076 HCl potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo. In cell models, S49076 HCl inhibited the proliferation of MET- and FGFR2-dependent gastric cancer cells blocked MET-driven migration of lung carcinoma cells, and inhibited colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 HCl was established and correlated well with impact on tumor growth.

R916562 is an orally active, selective Axl VEGF-R2 inhibitor with IC50 values of 136 nM and 24 nM, respectively, demonstrating anti-angiogenesis and anti-metastasis properties.

MerTK Axl-IN-1 (Compound A-910) is a potent and selective dual inhibitor of MerTK Axl, exhibiting IC50 values of 4.2 nM and 8.8 nM in Ba F3 cells, and 0.2 nM and 0.9 nM in HTRF cells, respectively. It effectively inhibits pMerTK in vivo and possesses a long half-life and high oral bioavailability.

AXL-IN-14 is a potent, orally active inhibitor of AXL with an IC50 of 0.8 nM that effectively suppresses Gas6 AXL-mediated cell migration and invasion, reduces the expression of p-AXL and p-AKT proteins, and demonstrates anti-tumor activity [1].