Mer Inhibitor

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.

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

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.

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

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).

UNC9426 is a potent and selective TYRO3 inhibitor (IC₅₀ = 2.1 nM), demonstrating 276-fold and 90-fold selectivity over MERTK and AXL, respectively. UNC9426 reduces platelet aggregation without increasing bleeding time and blocks TYRO3-dependent functions in tumor cells and macrophages. UNC9426 demonstrates a favorable safety profile with no significant increase in bleeding risk in vivo. UNC9426 can be used for functional studies of TYRO3-dependent phenotypes such as non-small cell lung cancer (NSCLC).

UNC2881 is an orally active and specific Mer kinase inhibitor, inhibits steady-state Mer kinase phosphorylation with an IC₅₀ value of 22 nM. UNC2881 shows additional inhibition against Axl and Tyro with IC₅₀s of 360 nM and 250 nM, respectively. UNC2881 potently inhibits collagen-induced platelet aggregation, can be used for pathologic thrombosis research.

PF-07265807 (ARRY-067) is a kinase inhibitor with primary targets AXL, MERTK, and TYRO3. PF-07265807 acts as an immunomodulator that cross-activates CD8⁺ T cells by enhancing dendritic cell function. PF-07265807 blocks downstream signal transduction of AXL and MERTK, and inhibits the proliferation and migration of tumor cells with high expression of these two kinases. PF-07265807 is applicable to research related to advanced or metastatic solid tumors, such as colorectal cancer.

Adrixetinib (Q702) is an orally active triple inhibitor against CSF1R, Mer, and Axl, with K_d values of 8.7 nM, 0.8 nM, and 0.3 nM, respectively. Adrixetinib acts as a potent immune modulator that remodels the tumor microenvironment. Adrixetinib increases the abundance of M1 macrophages and CD8⁺ T cells, while decreasing the levels of M2 macrophages and myeloid-derived suppressor cells (MDSCs). Adrixetinib upregulates the expression of MHC class I and E-cadherin in tumor cells. Adrixetinib shows remarkable antitumor efficacy in syngeneic mouse tumor models. Adrixetinib is suitable for the research of breast cancer, renal adenocarcinoma, colon carcinoma, and melanoma.

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

AZ14145845 is a highly selective type I1/2 dual Mer/Axl kinase inhibitor with in vivo efficacy.

Adrixetinib (Q702) TFA is an orally active triple inhibitor against CSF1R, Mer, and Axl, with K_d values of 8.7 nM, 0.8 nM, and 0.3 nM, respectively. Adrixetinib TFA acts as a potent immune modulator that remodels the tumor microenvironment. Adrixetinib TFA increases the abundance of M1 macrophages and CD8⁺ T cells, while decreasing the levels of M2 macrophages and myeloid-derived suppressor cells (MDSCs). Adrixetinib TFA upregulates the expression of MHC class I and E-cadherin in tumor cells. Adrixetinib TFA shows remarkable antitumor efficacy in syngeneic mouse tumor models. Adrixetinib TFA is suitable for the research of breast cancer, renal adenocarcinoma, colon carcinoma, and melanoma.

UNC8212 is a TAM kinase inhibitor. UNC8212 has potent inhibitory activity against MERTK and AXL (IC₅₀: 1.5 nM and 1.3 nM, respectively), and also inhibits TYRO3 (IC₅₀: 6.7 nM). UNC8212 mediates polypharmacological properties by targeting the structurally diverse "back pocket" region of the TAM kinase family. UNC8212 binds tightly to TAM kinases and potently inhibits MERTK and AXL phosphorylation. UNC8212 has anti-tumor effects and can be used in cancer immunotherapy and tumor cell targeting research.

Axl-IN-17 (compound 13c) is an orally active, selective AXL inhibitor with an IC₅₀ value of 3.2 nM. Axl-IN-17 reveals antitumor efficacy.

Axl/Mer-IN-1 (Compound 1) is an Axl/Mer receptor tyrosine kinase (Axl/Mer RTK) and CSF1R inhibitor with K_ds of <0.1 μM.

Axl-IN-21 is an orally active and selective AXL inhibitor (K_d = 2.7 nM, IC₅₀ = 4.0 nM). Axl-IN-21 displays kinase selectivity and retains strong activity against cancer-related mul-kinases (Mer with K_d = 1.4 nM, DDR1 with IC₅₀ = 22.2 nM, HIPK4 with K_d = 11.0 nM and LOK with K_d =10 nM). Axl-IN-21 overcomes tumor microenvironment-driven resistance by blocking CAF-derived GAS6-induced AXL/STAT3/ABCG1 signaling, restoring chemosensitivity and inhibiting drug efflux in gastric cancer (GC). Axl-IN-21 suppresses TGF-β1-induced epithelial-mesenchymal transition (EMT), migration, and invasion in MDA-MB-231 cells. Axl-IN-21 exhibits no significant cytotoxicity in non-cancerous cells. Axl-IN-21 can be research for triple negative breast cancer and gastric cancer^{[1] [2]} .

UNC3133 is an orally active, limitedly selective MerTK inhibitor with an IC₅₀ of 3.0 nM. UNC3133 inhibits Axl, Tyro3 and Flt3 kinases, with IC₅₀ values of 17 nM, 31 nM and 6.8 nM, respectively. UNC3133 is applicable to the research of inflammatory diseases and cancers.