| Identification | Back Directory | [Name]
Benzenesulfonamide, N-[2-chloro-5-(1H-pyrazolo[3,4-b]pyridin-5-yl)-3-pyridinyl]- | [CAS]
2050524-24-6 | [Synonyms]
FD223
N-(2-chloro-5-(1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)benzenesulfonamide
Benzenesulfonamide, N-[2-chloro-5-(1H-pyrazolo[3,4-b]pyridin-5-yl)-3-pyridinyl]- | [Molecular Formula]
C17H12ClN5O2S | [MDL Number]
MFCD34180346 | [MOL File]
2050524-24-6.mol | [Molecular Weight]
385.83 |
| Chemical Properties | Back Directory | [Boiling point ]
652.7±65.0 °C(Predicted) | [density ]
1.556±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (259.18 mM; Need ultrasonic) | [form ]
Solid | [pka]
6.54±0.40(Predicted) | [color ]
Off-white to brown |
| Hazard Information | Back Directory | [Uses]
FD223 is a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. FD223 displays high potency (IC50=1 nM) and good selectivity over other isoforms (IC50s of 51 nM, 29 nM and 37 nM, respectively for α, β and γ). FD223 exhibits efficient inhibition of the proliferation of acute myeloid leukemia (AML) cell lines by suppressing p-AKT Ser473 thus causing G1 phase arrest during the cell cycle. FD223 has potential for the research of leukemia such as AML[1]. | [Biological Activity]
FD223 is a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. FD223 displays high potency (IC50=1 nM) and good selectivity over other isoforms (IC50s of 51 nM, 29 nM and 37 nM, respectively for α, β and γ). FD223 exhibits efficient inhibition of the proliferation of acute myeloid leukemia (AML) cell lines by suppressing p-AKT Ser473 thus causing G1 phase arrest during the cell cycle. FD223 has potential for the research of leukemia such as AML[1].
FD223 exhibits notable anti-proliferative activities in the p110δ-positive AML cell lines HL-60, MOLM-16, EOL-1 and KG-1, with the IC50 of 2.25 μM, 0.87 μM, 2.82 μM, and 5.82 μM, respectively. FD223 shows weak anti-proliferative activity against p110δ unexpressed MM.1R cell line, with the IC50 value of 23.13 μM[1].FD223 (MOLM-16 cells; 0.1-5 μM; 16 hours) dose-dependently reduces phosphorylation of Akt (Ser473), which is consistent with the positive control Idelalisib, illustrating that the activity of PI3K/Akt pathway in MOLM-16 cell is blocked[1].FD223 (MOLM-16 cells; 24 hours; 1-5 μM) arrests the cell cycle at the G1 phase similar to that of positive control Idelalisib[1].FD223 (1-5 μM; 48 hours) dose-dependently induces cellular apoptosis[1].
FD223 (20 and 40 mg/kg; p.o, per day for 14 consecutive days) displays potent antitumor efficacy in MOLM-16 xenograft model with the tumor volume reduction of 49% at a dose of 40 mg/kg/day (po), and shows no significant toxicity in the preliminary safety assessment[1].FD223 (i.v.; dose of 2 mg/kg; p.o.; 10 mg/kg rats) shows a moderate plasma clearance rate after intravenous administration with C =0.191 L?h-1?kg-1. In the po route, it shows a half-life (t1/2) of 3.74 h and a Cmax of 1104 ng/mL, good oral plasma exposures (AUC0-∞>9000 h?ng/mL) and acceptable oral bioavailability (17.6%)[1]. | [in vivo]
FD223 (20 and 40 mg/kg; p.o, per day for 14 consecutive days) displays potent antitumor efficacy in MOLM-16 xenograft model with the tumor volume reduction of 49% at a dose of 40 mg/kg/day (po), and shows no significant toxicity in the preliminary safety assessment[1].
FD223 (i.v.; dose of 2 mg/kg; p.o.; 10 mg/kg rats) shows a moderate plasma clearance rate after intravenous administration with C =0.191 L?h-1?kg-1. In the po route, it shows a half-life (t1/2) of 3.74 h and a Cmax of 1104 ng/mL, good oral plasma exposures (AUC0-∞>9000 h?ng/mL) and acceptable oral bioavailability (17.6%)[1]. | Animal Model: | MOLM-16 xenograft model of BALB/c nude mice[1] | | Dosage: | 20 and 40 mg/kg | | Administration: | P.o, per day for 14 consecutive days | | Result: | Showed a dose-dependent tumor growth inhibition (TGI) of 31% for 20 mg/kg and 49% for 40 mg/kg
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| [IC 50]
PI3Kδ: 1 nM (IC50); PI3Kα: 51 nM (IC50); PI3Kβ: 29 nM (IC50); PI3Kγ: 37 nM (IC50) | [References]
[1]. Yang C, et al. Bioisosteric replacements of the indole moiety for the development of a potent and selective PI3Kδ inhibitor: Design, synthesis and biological evaluation [published online ahead of print, 2021 Jun 21]. Eur J Med Chem. 2021;223:113661. |
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