FPFT-2216 (C09-1134-001)

FPFT-2216, a “molecular glue” compound, degrades phosphodiesterase 6D ( PDE6D ), zinc finger transcription factors Ikaros ( IKZF1 ), Aiolos ( IKZF3 ), and casein kinase 1α ( CK1α ). FPFT-2216 can be used for the research of cancer and inflammatory diseaseIn VitroFPFT-2216 (1 μM; 5 hours) is able to degrade PDE6D, in addition to its known targets IKZF1, IKZF3, and CK1α in MOLT4 cells. FPFT-2216 (1 μM; 0 h, 2 h, 4 h, 6 h, 16 h, 24 h) shows complete degradation of PDE6D within 2 h, and the degradation of PDE6D persists for at least 24 h in MOLT4 cells. FPFT-2216 (0 nM, 1.6 nM, 8 nM, 40 nM, 200 nM, 1 μM; 4 h) exhibits over 50% degradation of PDE6D at a dose of 8 nM, while maximum degradation of PDE6D along with IKZF1, IKZF3, and CK1α at a dose of 200 nM in MOLT4 cells. FPFT-2216 does not impede the growth of KRAS G12C -dependent MIA PaCa-2 cells. FPFT-2216 (10, 20, 40 µM; 14 or 24 h) highly up-regulates the production of IL-2 although it is less potent than that of Pomalidomide in Naive CD4 + T cells. FPFT-2216 (10 µM; 14 or 24 h) degrades IKZF1 and CK-1α among ubiquitin–proteasomal degradative substrates of immunomodulatory drugs (IMiDs) in Naive CD4 + T cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: MOLT4 cells Concentration: 1 μM Incubation Time: 0 h, 2 h, 4 h, 6 h, 16 h, 24 h Result: Showed complete degradation of PDE6D within 2 h, and the degradation of PDE6D persisted for at least 24 h. Western Blot AnalysisCell Line: MOLT4 cells Concentration: 0 nM, 1.6 nM, 8 nM, 40 nM, 200 nM, 1 μM Incubation Time: 4 h Result: Exhibited over 50% degradation of PDE6D at a dose of 8 nM, while maximum degradation of PDE6D along with IKZF1, IKZF3, and CK1α at a dose of 200 nM.In VivoFPFT-2216 (30 mg/kg; p.o. or i.p.) induces significant degradation of CK-1α, and IKZF1 in CRBN I391V mice. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: CRBN I391V miceDosage: 30 mg/kg (solubilized in 0.5% carboxymethylcellulose/sodium and 0.25% Tween 80) Administration: p.o. or i.p. Result: Induced significant degradation of CK-1α, and IKZF1.IC50& Target:PDE6D CK1α IKZF1 IKZF3. Specification: 10mM in DMSO Molecular Formula: C12H12N4O3S Molecular Weight: 292.31