csf1r-in-2

CSF1R-IN-2 is an oral-active SRC, MET and c-FMS inhibitor (IC50s: 0.12 nM, 0.14 nM and 0.76 nM for SRC, MET and c-FMS respectively).

Axl Mer CSF1R-IN-2 (Comp 4) serves as an inhibitor for Axl, Mer, and CSF1R [1].

CSF1R-IN-26 (Compound III-1) is an inhibitor of CSF-1R with an IC50 of 20.07 nM. It promotes the polarization of M2 macrophages to M1 macrophages, inducing apoptosis in MC-38 cancer cells. CSF1R-IN-26 inhibits the activation of the AKT/ERK/STAT3 signaling pathways, remodels the tumor immune microenvironment, and exhibits antitumor activity in mouse models. In SD rats, CSF1R-IN-26 demonstrates favorable pharmacokinetic properties, with a half-life of 1.86 hours and an oral bioavailability of 79.22%.

CSF1R-IN-20 (compound 7a), a CSF-1R inhibitor, exhibits an IC 50 of 467 nM and effectively inhibits CSF-1R auto-phosphorylation [1].

CSF1R-IN-21 (compound 7e), a CSF-1R inhibitor, exhibits potent inhibition with an IC 50 of 31 nM and effectively blocks CSF-1R auto-phosphorylation. It is utilized in researching neurodegenerative diseases [1].

CSF1R-IN-22 (Compound C19), a potent orally administered CSF-1R selective inhibitor (IC50 <6 nM), significantly enhances CXCL9 secretion from M2 macrophages and promotes CD8+ T cell infiltration. Moreover, it amplifies the anti-tumor immune responses in conjunction with anti-PD-1 and triggers apoptosis in tumor cells. Additionally, CSF1R-IN-22 effectively reprograms M2-like TAMs (tumor-associated macrophages) to an M1 phenotype, modulates the tumor microenvironment (TME) by fostering the recruitment of CD8+ T cells, and diminishes the presence of immunosuppressive Tregs and MDSCs [1].

CSF1R-IN-23 (Compound 7dri), a selective colony-stimulating factor-1 receptor (CSF1R) inhibitor, exhibits an IC50 of 36.1 nM. This compound acts as an antineuroinflammatory agent in a mouse model and is noted for its blood-brain barrier (BBB) permeability [1].

CSF1R-IN-24 (Example 134), an orally active inhibitor of CSF1R, effectively reduces the survival of human iPSC-derived microglia (hiPSC-MG).

PLX5622 hemifumarate is a highly selective, blood-brain barrier-permeable, and orally active CSF1R inhibitor with an IC50 of 0.016 μM and a Ki of 5.9 nM. It can be used to eliminate proliferating and specific microglia before and during disease progression and is applicable for inducing Alzheimer's disease models.

Sulfatinib (KDR-IN-1) (HMPL-012) is a potent and highly selective tyrosine kinase inhibitor against VEGFR1/2/3, FGFR1 and CSF1R with IC 50 s ranging from 1 to 24 nM.

Cabiralizumab (FPA 008), an anti-CSF1R monoclonal antibody (MAb), promotes T cell infiltration and boosts antitumor immune responses. It also prevents osteoclast activation, thereby inhibiting bone destruction, and is utilized in rheumatoid arthritis (RA) research. Additionally, Cabiralizumab can be paired with Nivolumab in lung cancer studies [1] [2].