Mecbotamab is a humanized IgG1-κ antibody targeting to AXL receptor tyrosine kinase (AXL). Mecbotamab can serves as a conditionally active biologic (CAB), which can be conjugated with MMAE (HY-15162) via a cleavable linker, to form ADC Mecbotamab vedotin (BA3011)[1][2].
Axl-IN-9 (Example 10) is a potent AXL inhibitor, with an IC50 of 26 nM. Axl-IN-9 has excellent transmembrane properties. Axl-IN-9 exhibits excellent pharmacokinetic properties in an animal body. Axl-IN-9 can be used for the research of proliferative diseases, autoimmune diseases, allergic diseases, inflammatory diseases, transplant rejection, cancer, or other diseases in mammals[1].
ONO-7475 is a potent, selective, and orally active novel Axl/Mer inhibitor with IC50 values of 0.7 nM and 1.0 nM, respectively. ONO-7475 sensitizes AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs, suppresses the emergence and maintenance of tolerant cells. ONO-7475 combines with Osimertinib (HY-15772) provides a bright promise for the study of EGFR-mutated non-small cell lung cancer (NSCLC)[1].
Axl-IN-7 (Chemie 22) is a potent AXL inhibitor. Axl-IN-7 can be used for Axl-related diseases research, for example cancers (such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glial tumors), renal disease, immune system disorders, and cardiovascular disease[1].
UNC2881 is a potent and specific Mer kinase inhibitor; inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. IC50 value: 22 nM [1]Target: Mer kinase inhibitorTreatment with UNC2281 is also sufficient to block EGF-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, UNC2881 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis.
Axl-IN-10 (Example 1) is a potent AXL inhibitor, with an IC50 of 5 nM. Axl-IN-10 has excellent transmembrane properties.Axl-IN-10 exhibits excellent pharmacokinetic properties in an animal body. Axl-IN-10 can be used for the research of proliferative diseases, autoimmune diseases, allergic diseases, inflammatory diseases, transplant rejection, cancer, or other diseases in mammals[1].
Axl-IN-5 (compound 1) is a AXL inhibitor with an IC50 of 283 nM. Axl-IN-5 has anticancer effects[1].
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)[1].
Glesatinib hydrochloride is an inhibitor of the MET and Axl receptor tyrosine kinase pathways, which drive tumour growth when altered.Target: MET, AxlGlesatinib is an orally bioavailable, small-molecule, multitargeted tyrosine kinase inhibitor with potential antineoplastic activity. MGCD265 binds to and inhibits the phosphorylation of several receptor tyrosine kinases (RTKs), including the c-Met receptor (hepatocyte growth factor receptor); the Tek/Tie-2 receptor; vascular endothelial growth factor receptor (VEGFR) types 1, 2, and 3; and the macrophage-stimulating 1 receptor (MST1R or RON). Glesatinib is a tyrosine kinase inhibitor that is expected to potently and selectively target tumors in patients with driver alterations in MET (mutations and gene amplification) and Axl (rearrangements) that occur in approximately 8% of patients with non-small cell lung cancer (NSCLC). Glesatinib is being evaluated in a Phase 1b study in patients with solid tumors that have genetic alterations in MET or AXL genes. The Phase 2 trial in NSCLC patients with MET genetic alterations is underway to confirm and extend the data that supports the clinical benefit of Glesatinib in patients with driver mutations in MET. Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC, gastroesophageal cancer and other solid tumors. MET and Axl are also implicated as drivers of tumor progression in patients whose tumors have become resistant to EGFR inhibitors. Therefore, Mirati believes that the combination of Glesatinib with an EGFR inhibitor could potentially treat patients who have become resistant to agents targeting EGFR. Mirati retains worldwide rights to Glesatinib.
Gilteritinib-d8 is deuterium labeled Gilteritinib. Gilteritinib (ASP2215) is a potent and ATP-competitive FLT3/AXL inhibitor with IC50s of 0.29 nM/0.73 nM, respectively.
RU-302 is a pan TAM inhibitor that blocks the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. RU-302 effectively blocks Gas6-inducible Axl receptor activation with a low micromolar IC50in cell assays, and suppresses lung cancer tumor growth[1].
Axl-IN-6 (compound 14) is an orally active and potent AXL inhibitor. Axl-IN-6 is well tolerated and significantly inhibits the tumor growth in MV-4-11 subcutaneous xenograft model[1].
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.
Gilteritinib is a potent FLT3/AXL inhibitor with IC50s of 0.29 nM/0.73 nM, respectively.
UNC4203 (UNC-4203) is a potent, highly selective MerTK with IC50 of 2.4 nM, displays >30- and 4 -foldfold selectivity over Alx (IC50=80 nM) and Tyro3 (IC50=9.1 nM); display IC50 of 39 nM for FLT-3, inhibits MERTK phosphorylation in cell-based assays with IC50 of 13.8 nM, inhibits MERTK phosphorylation in vivo in mice with advanced leukemia (30 mg/kg, ip injection).
Ningetinib Tosylate is a potent, orally bioavailable small molecule tyrosine kinase inhibitor (TKI) with IC50s of 6.7, 1.9 and <1.0 nM for c-Met, VEGFR2 and Axl, respectively.
Mipasetamab is an IgG1κ antibody targeting to AXL, a tyrosine kinase receptor and an TAM Receptor. Mipasetamab involves in synthesis of ADCT-601 (Mipasetamab uzoptirine), an AXL-targeted antibody-drug conjugate (ADC). ADCT-601 has anti-tumor activity[1].
Axl-IN-8 (NO.1) is a potent AXL inhibitor, with an IC50 of <1 nM. Axl-IN-8 also inhibits c-MET, with an IC50 of 1-10 nM. Axl-IN-8 shows anti-proliferative activity against BaF3/TEL-AXL, MKN45, and EBC-1 cells, with IC50 values of <10, 226.6 and 120.3 nM, respectively[1].
UNC2250 is a phosphorylation of endogenous Mer inhibitor with an IC50 of 9.8 nM and blocked ligand-stimulated activation of a chimeric EGFR-Mer protein.IC50 Value: 9.8 nM [1]Target: Othersin vitro: UNC2250 is 160-fold more active for Mer versus Axl and 60-fold versus Tyro3. UNC2250 had a moderate half-life, clearance, and volume of distribution as well as reasonable oral bioavailability and good solubility and was thus chosen for characterization of kinase selectivity and further evaluation in cell-based studies of Mer activity. UNC2250 efficiently inhibited ligand-dependent phosphorylation of a chimeric protein consisting of the extracellular and transmembrane domains of the epidermal growth factor (EGF) receptor and the intracellular tyrosine kinase domain of Mer. Moreover, UNC2250 incubation inhibited colony formation in soft agar cultures of the BT-12 rhabdoid tumor and the Colo699 NSCLC cell lines. In the Colo699 NSCLC cell line, the concentrations of UNC2250 required to inhibit colony formation and Mer phosphorylation were similar. These data suggest that the functional antiproliferative activity mediated by UNC2250 resulted from Mer inhibition rather than a consequence of off-target inhibition of other kinases [1,2].In vivo: