Cabozantinib-d4 is deuterium labeled Cabozantinib. Cabozantinib is a potent multiple receptor tyrosine kinases (RTKs) inhibitor that inhibits VEGFR2, c-Met, Kit, Axl and Flt3 with IC50s of 0.035, 1.3, 4.6, 7 and 11.3 nM, respectively.
R916562 is a potential and selective Axl/VEGF-R2 dual inhibitor with IC50s of 136 and 24 nM, respectively.
Mipasetamab uzoptirine (ADCT-601) is an AXL-targeted antibody-drug conjugates (ADCs). Mipasetamab uzoptirine consists of a humanized anti-AXL antibody, a cleavable linker and the potent pyrrolobenzodiazepine (PBD) dimer cytotoxin SG3199. Mipasetamab uzoptirine can be used for the research of cancers[1].
SGI-7079 is an Axl inhibitor, significantly inhibits the proliferation of SUM149 or KPL-4 cells with an IC50 of 0.43 or 0.16 μM, respectively.Ic50 value:Target: Axlin vitro: SGI-7079 treatment inhibits the phosphorylation of Axl at Tyr 702 upon Gas6 stimulation in SUM149 cells. The growth of SUM149 and KPL-4 in soft agar, one of the hallmark characteristics of cellular transformation and uncontrolled cell growth, is also significantly inhibited by SGI-7079 treatment. SGI-7079 treatment also significantly decreases the migration and invasion of SUM149 cells and the invasion of KPL-4 cells. Taken together, Axl inhibitor SGI-7079 significantly inhibits the proliferation, migration, and invasion of IBC cells, suggesting that Axl may be a promising therapeutic target in patients with IBC. [1]in vivo: SGI-7079 inhibits tumor growth in a dose dependent manner, and at the maximum dose, inhibited tumor growth by 67%, compared to control. The combined inhibition of Axl (SGI-7079) plus EGFR (Erlotinib) is significantly more effective than either drug alone. Notably, SGI-7079 + Erlotinib (25/100 mg/kg) reduced the tumor growth by 82%. Axl blockade by SGI-7079 inhibits the growth of mesenchymal NSCLC xenograft tumors. [2]
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.
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.
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:
PF-07265807 (PF 07265807) is a potent, selective dual Axl/Mer inhibitor, blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells.
2-D08 is a cell permeable, mechanistically unique inhibitor of protein SUMOylation. 2-D08 also inhibits Axl with an IC50 of 0.49 nM.
Axl-IN-12 (Example 2) is a potent AXL inhibitor. Axl-IN-12 can be used for the research of proliferative diseases, autoimmune diseases, allergic diseases, inflammatory diseases, transplant rejection, cancers, viral infectious diseases or other diseases of mammals[1].
TL4830031 (compound 8i), a quinolone antibiotic derivatives, is a potent Axl inhibitor with an IC50 value of 26 nM. TL4830031 inhibits the phosphorylation of Axl. TL4830031 inhibits cell invasion and migration. TL4830031 can be used for cancer research[1].
Cabozantinib hydrochloride is a potent and orally active inhibitor of VEGFR2 and MET, with IC50 values of 0.035 and 1.3 nM, respectively. Cabozantinib hydrochloride displays strong inhibition of KIT, RET, AXL, TIE2, and FLT3 (IC50=4.6, 5.2, 7, 14.3, and 11.3 nM, respectively). Cabozantinib hydrochloride shows antiangiogenic activity. Cabozantinib hydrochloride disrupts tumor vasculature and promotes tumor and endothelial cell apoptosis[1].
TAM-IN-2 is a TAM inhibitor extracted from patent US 20170275290 A1, pyrrolotriazine compound 0904[1].
Multi-kinase-IN-1 (Compound 11k) is a potent kinase inhibitor with antitumor activity. Multi-kinase-IN-1 induces cell apoptosis, and can be studied for colorectal cancer[1].
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].
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].
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.
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].