Adrixetinib

Adrixetinib (Q702) is an orally active triple inhibitor against CSF1R, Mer, and Axl, with Kd values of 8.7 nM, 0.8 nM, and 0.3 nM, respectively. Adrixetinib (Q702) acts as a potent immune modulator that remodels the tumor microenvironment, increasing M1 macrophages and CD8⁺ T cells while decreasing M2 macrophages and myeloid-derived suppressor cells (MDSCs). Adrixetinib (Q702) upregulates MHC class I and E-cadherin in tumor cells and shows efficacy in syngeneic mouse tumor models. Adrixetinib (Q702) is utilized in oncology research focused on tumor microenvironment reprogramming, macrophage polarization dynamics, and immune cell infiltration in breast cancer, renal adenocarcinoma, colon carcinoma, and melanoma models.

Mer:0.8 nM (Kd), Axl:0.3 nM (Kd)

Methods：Target inhibitory activity was detected via in vitro kinase assay. Multiple tumor cell lines were pretreated with gradient drug concentrations, and phosphorylation levels of pathway proteins were determined. The effects of the compound on tumor cell proliferation and viability were evaluated.
Results：
1.After 1-hour incubation, adrixetinib potently inhibited Axl, Mer and CSF1R kinases with IC₅₀ values of 0.3 nM, 0.8 nM and 8.7 nM respectively.
2.Adrixetinib blocked ligand-induced phosphorylation of Axl, Mer, CSF1R and downstream pathway proteins in a concentration-dependent manner.
3.Adrixetinib reduced EMT6 cell viability after 72-hour treatment with an IC₅₀ of 8.4 μM. It suppressed M-NFS-60 cell proliferation via inhibiting CSF1R pathway, with the IC₅₀ lower than 1.0 μM [1-2].

Methods：Multiple allogeneic and syngeneic mouse tumor models were established. Oral administration was performed at diverse doses and cycles. Target phosphorylation, tumor growth, gene expression, immune cell infiltration and levels of related molecules and cytokines were detected.
Results：
1.Oral administration of adrixetinib at 30 mg/kg daily for 7 days inhibited the phosphorylation of Axl and CSF1R in xenograft tumors of nude mice.
2.Treatment with adrixetinib at 10–100 mg/kg for 14 days suppressed breast tumor growth in a dose-dependent manner, with tumor inhibition rates ranging from 54.3% to 84.6%.
3.Adrixetinib regulated tumor gene expression and reshaped intratumoral immune composition. It upregulated MHC-I and E-cadherin to form an immune-activated microenvironment.
4.The drug promoted secretion of IFN-γ and granzyme B, enhanced cytotoxicity of T cells and NK cells, increased intratumoral infiltration of CD8⁺ T cells and reduced myelocyte accumulation.
5.Adrixetinib exerted prominent anti-tumor effects on multiple mouse tumor models including melanoma and colorectal carcinoma, with tumor growth inhibition rates of 64%–77% [1].

DMSO: 80 mg/mL (150.52 mM), Sonication is recommended.