TFC 007

TFC-007 is a selective and orally effective hematopoietic prostaglandin D synthase (H-PGDS) inhibitor, with an IC₅₀ of 71 nM for H-PGDS. TFC-007 shows weak effects on L-PGDS and various arachidonic acid-related enzymes and receptors. TFC-007 inhibits PGD2 production in KU812 cells without decreasing H-PGDS protein levels. TFC-007 can be used for research on H-PGDS/PGD2 signaling and allergic rhinitis^{[1][2][3][4][5]}. In Vitro:The logD of TFC-007 is 3.06^[1].
The PBS solubility of TFC-007 (100 μM; 10 min) is 3.17 μM^[1].
TFC-007 (4 h) exhibits a P_app of 3.01 × 10^-6 cm/s in the PAMPA artificial membrane system^[1].
After incubation in human liver microsomes for 10 and 60 min, TFC-007 (10-60 min) retains 96% and 80% of the unchanged product, respectively^[1].
TFC-007 binds to H-PGDS in a competitive fluorescence polarization assay with an IC₅₀ of 0.32 μM^[2].
TFC-007 (10 μM; 3 h) inhibits ligand binding to the H1 receptor in human recombinant CHO cell membranes by 17%^[5].
TFC-007 inhibits H-PGDS enzymatic activity with an IC₅₀ of 71 nM^[2].
TFC-007 (1 μM; in combination with 1 μM Pomalidomide (HY-10984); 6 h) does not effectively reduce H-PGDS protein levels in KU812 cells^[2].
TFC-007 (10-100 nM; 24 h) does not decrease H-PGDS protein levels in KU812 cells^[2].
TFC-007 (10-100 nM; 24 h; after 4 washes and incubation in compound-free medium for 6 h) still does not induce a decrease in H-PGDS protein in KU812 cells^[2].
TFC-007 (10-100 nM; 24 h; followed by stimulation with 5 μM A23187 (HY-N6687) for 30 min in the presence of TFC-007) decreases PGD2 production in KU812 cells^[2].
The inhibitory effect of TFC-007 (10-100 nM; 24 h; after 4 washes and 6 h incubation without compound; followed by stimulation with 5 μM A23187 for 30 min) on PGD2 production in KU812 cells disappears, and PGD2 production recovers^[2].
TFC-007 exhibits an IC₅₀ of 211.2 nM against H-PGDS in a competitive fluorescence polarization assay^[4].
TFC-007 (10 μM; combined with 1 nM PROTAC 2; 6 h) inhibits PROTAC 2-induced H-PGDS protein reduction in KU812 cells^[4].
TFC-007 (10 nM; 24 h; followed by stimulation with 5 μM A23187 for 30 min) decreases PGD2 levels in the culture medium of KU812 cells^[4].
TFC-007 (0.1-100 μM; preincubation for 5 min; PGH2 reaction for 1 min) concentration-dependently inhibits human recombinant H-PGDS activity with an IC₅₀ of 0.083 μM^[5].
TFC-007 (10 μM; 30 min) shows an inhibition rate of -1% on ligand binding to the CysLT1 receptor in human recombinant CHO-K1 cell membranes^[5].
TFC-007 (10 μM; 30 min) shows an inhibition rate of -2% on ligand binding to human recombinant HEK-293 cell membrane TP receptors^[5]. In Vivo:TFC-007 (30 mg/kg; p.o.; single dose; 1 h before challenge) attenuates late-phase nasal obstruction 3-8 h after antigen challenge in Japanese cedar pollen-induced allergic rhinitis male Hartley guinea pigs, but does not affect the sneezing response within 1 h after challenge or early-phase nasal obstruction 0-3 h^[5].
TFC-007 (30 mg/kg; p.o.; single dose; 1 h before challenge) almost completely inhibits the increase in PGD2 in nasal lavage fluid 20 min after antigen challenge and reduces the increase in PGD2 at 5 h in Japanese cedar pollen-induced allergic rhinitis male Hartley guinea pigs, but does not inhibit the increases in CysLTs and TXB2 at 20 min or 5 h^[5].
TFC-007 (30 mg/kg; p.o.; single dose; 1 h before challenge) does not inhibit the increase in eosinophils in nasal lavage fluid 5 h after antigen challenge in Japanese cedar pollen-induced allergic rhinitis male Hartley guinea pigs, nor does it affect the increases in monocyte populations and neutrophils^[5].
TFC-007 (30 mg/kg; p.o.; single dose; 1.5 h after challenge) markedly inhibits the increase in PGD2 in nasal lavage fluid 5 h after antigen challenge in Japanese cedar pollen-induced allergic rhinitis male Hartley guinea pigs, but does not alleviate nasal obstruction 2-8 h after challenge^[5].