OSI-930 is a potent inhibitor of Kit, KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively; also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl.IC50 value: 9 nM(VEGFR2); 15 nM(CSF1R); 80 nM (Kit activated) [1]Target: VEGFR2/Kit/CSF1Rin vitro: OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. Moreover, OSI-930 also induces apoptosis in HMC-1 cell line with EC50 of 34 nM [1]. A recent study shows that OSI-930 inactivates purified, recombinant cytochrome P450 (P450) 3A4 with a Ki of 24 μM in a time- and concentration-dependent mode [2].in vivo: OSI-930, administrated at the maximally efficacious dose of 200 mg/kg by oral gavage, exhibits potent antitumor activity in a broad range of preclinical xenograft models including HMC-1, NCI-SNU-5, COLO-205 and U251 xenograft models [1].
Axl/Mer-IN-1 (Compound 1) is an Axl/Mer receptor tyrosine kinase (Axl/Mer RTK) and CSF1R inhibitor with Kds of <0.1 μM[1].
Lacnotuzumab (MCS110) is a neutralizing humanized IgG1/κ monoclonal antibody targeting CSF-1 that prevents CSF-1 from activating the CSF-1R. Lacnotuzumab can be used for the research of pigmented villonodular synovitis[1][2].
BPR1R024 is an orally active and selective CSF1R inhibitor (IC50 = 0.53 nM).
Pimicotinib is a CSF1R inhibitor with antitumor activity[1].
CSF1R-IN-1 is a CSF1R inhibitor with an with an IC50 of 0.5 nM.
cFMS-IN-2 is a FMS kinase inhibitor with an IC50 of 0.024 μM.
Ki-20227 is a highly selective c-Fms tyrosine kinase(CSF1R) inhibitor with IC50 value of 2 nM; 6 fold and > 100 fold selectivity over VEGFR2(IC50=12 nM) and c-Kit/PDGFRβ(IC50=451/217 nM), respectively.IC50 value: Target: CSF1Rin vitro: Ki20227 did not inhibit other kinases tested, such as fms-like tyrosine kinase-3, epidermal growth factor receptor, or c-Src (c-src proto-oncogene product). Ki20227 was also found to inhibit the M-CSF-dependent growth of M-NFS-60 cells but not the M-CSF-independent growth of A375 human melanoma cells in vitro [1]. Ki20227 inhibited M-CSF-dependent reactions, such as lipopolysaccharide-induced tumor necrosis factor-alpha production, which were enhanced by M-CSF in vitro [2]. in vivo: Ki20227 decreased the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats [1]. In addition, the number of CD11b(+), Gr-1(+), and Ly-6G(+) cells in the spleen decreased in the Ki20227-treated mice, and the CII-induced cytokine production in splenocytes isolated from the Ki20227-treated arthritic mice was also reduced [2]. Ki20227 treatments inhibited the turn-over/expansion of myeloid cells provoked by the immunization and subsequent MOG-specific T cell responses in our EAE animal model [3].
PF 477736 is a potent, selective ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, 100-fold selectivity versus Chk2 (Ki, 47 nM).
Plonmarlimab (TJ003234) is an anti-GM-CSF monoclonal antibody. Plonmarlimab can be used for research of rheumatoid arthritis and COVID-19[1][2].
Pexidartinib (PLX-3397) is a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 13 nM, 27 nM, and 11 nM for CSF1R, c-Kit, and FLT3, respectively.
Mavrilimumab (CAM 3001) is a monoclonal antibody that binds to the α subunit of the granulocyte-macrophage colony stimulating factor (GM-CSF) receptor and blocks intracellular signalling downstream of GM-CSF. GM-CSF might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death[1].
IHMT-TRK-284 (Compound 34) is a potent, orally active type II TRK kinase inhibitor with IC50 values of 10.5, 0.7, and 2.6 nM to TRKA, B, and C respectively. IHMT-TRK-284 displays great selectivity profile in the kinome and good in vivo antitumor efficacies[1].
CSF1R-IN-15 (compound 23) is an inhibitor targeting CSF1R. The colony-stimulating factor-1 receptor (CSF1R) is a tyrosine kinase embedded in the cell membrane of macrophages. The receptor is activated by colony-stimulating factor-1 (CSF-1) and interleukin-34, and signaling via CSF1R is crucial for the differentiation, proliferation, and survival of macrophages[1].
IACS-9439 is a potent, selective, and orally active CSF1R inhibitor with a Ki value of 1 nM inhibitor. IACS-9439 can be used for advanced solid tumors research[1].
RET-IN-19 (compound 59) is a potent RET inhibitor, with IC50 values of 6.8 and 13.51 nM against RET-wt and RET V804M, respectively. RET-IN-19 shows anticancer activity. RET-IN-19 can be used for non-small cell lung cancer (NSCLC) research[1].
Axatilimab (SNDX-6352) is a humanized IgG4 antibody with high affinity to CSF-1R. Axatilimab can be used for the research of chronic graft versus host disease (cGVHD) and neoplastic diseases[1][2].
Namilumab (AMG203) is a human IgG1 monoclonal antibody that binds with high affinity to the GM-CSF ligand, potently neutralizing GM-CSF. Namilumab can be used for the research of rheumatoid arthritis[1].
cFMS Receptor Inhibitor II is a CSF1R kinase inhibitor. CSF-1 is a cytokine[1].
BPR1R024 mesylate is an orally active and selective colony-stimulating factor-1 receptor (CSF1R) inhibitor.BPR1R024 mesylate is the equivalent of BPR1R024 (HY-132935). BPR1R024 has potent CSF1R inhibition activity with an IC50 value of 0.53 nM. BPR1R024 can be used for the research of immuno-oncology[1].
Cabiralizumab (FPA 008) is an anti-CSF1R monoclonal antibody (MAb). Cabiralizumab enhances T cell infiltration and antitumor T cell immune responses. Cabiralizumab inhibits the activation of osteoclasts and blocks bone destruction, and can be used in the research of rheumatoid arthritis (RA). Cabiralizumab can combine with Nivolumab (HY-P9903) for lung cancer research[1][2].
Eflapegrastim is a humanized IgG4 monoclonal antibody, is also a granulocyte colony-stimulating factor (G-CSF). Eflapegrastim targets to G-CSF receptor (c-Fms). Eflapegrastim stimulates proliferation and differentiation of neutrophil progenitor cells and maintains stable numbers of mature and functional neutrophils. Eflapegrastim also shortens the duration of neutropenia[1].
Gimsilumab (MORAb-022) is a humanized anti-GM-CSF monoclonal antibody. Gimsilumab has the potential for the research of COVID-19 and rheumatoid arthritis (RA)[1][2].
GW2580 is an orally bioavailable inhibitor of c-Fms kinase which completely inhibits human cFMS kinase in vitro at 0.06 μM.
CSF1R-IN-2 (compound 5) is an oral-active inhibitor of SRC, MET and c-FMS, with IC50 values of 0.12 nM, 0.14 nM and 0.76 nM for SRC, MET and c-FMS respectively[1].
c-Fms-IN-7 is a cFMS inhibitor extracted from patent WO2011079076A1, example159, has an IC50 of 18.5 nM[1].
c-Fms-IN-14 (Example 76) is a c-Fms inhibitor with an IC50 value of 4 nM. c-Fms-IN-14 can be used for research of cancer and autoimmune diseases[1].
CSF1R-IN-9 (Compound 46) is a CSF-1R inhibitor with an IC50 of 0.028 μM[1].
PLX647 is a highly specific dual FMS/KIT kinase inhibitor with IC50 of 28/16 nM respectively.IC50 value: 28/16 nM(FMS/KIT) [1]Target: FMS/KIT dual inhibitorin vitro: PLX647 was tested against a panel of 400 kinases at a concentration of 1 μM, 35-fold above its FMS enzymatic IC50 and 60-fold above its KIT enzymatic IC50. In addition to FMS and KIT, the activities of only nine kinases were inhibited by more than 50%. PLX647 potently inhibits the growth of FLT3–ITD-expressing MV4-11 cells (IC50 = 0.11 μM) but not OCI-AML5 (IC50 = 1.6 μM), which express wild-type FLT3. PLX647 displayed minimal inhibition of the proliferation of Ba/F3 cells expressing BCR–KDR (IC50 = 5 μM) [1]. in vivo: PLX647 (40 mg/kg) was dosed orally 4.25 h before LPS injection. Treatment with PLX647 reduced serum TNF-α levels by 85% compared with the vehicle control. In the same experiment, the positive control dexamethasone (0.5 mg/kg, PO) lowered the TNF-α levels by 96%. Treatment with 40 mg/kg PLX647 also resulted in significant inhibition of IL-6 release (75%), with similar potency to dexamethasone (70%) . In the UUO kidneys, treatment with PLX647 [40 mg/kg twice daily (BID)] resulted in reduction in the levels of F4/80+ macrophages by 77% compared with vehicle [1].
Sotuletinib (BLZ945) dihydrochloride is an orally active and blood-brain barrier-permeable CSF1-R-specific inhibitor (IC50=1 nM). Sotuletinib (BLZ945) dihydrochloride induces tumor cell apoptosis and effectively inhibits tumor growth in mouse models. Sotuletinib dihydrochloride can be used in cancer and amyotrophic lateral sclerosis (ALS) research[1].