| Identification | Back Directory | [Name]
5-Pyrimidinecarbonitrile, 2,4-diamino-6-[[(1S)-1-[7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4H-quinolizin-2-yl]ethyl]amino]- | [CAS]
2101518-75-4 | [Synonyms]
PI3Kδ-IN-8
5-Pyrimidinecarbonitrile, 2,4-diamino-6-[[(1S)-1-[7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4H-quinolizin-2-yl]ethyl]amino]- | [Molecular Formula]
C28H21F2N7O | [MDL Number]
MFCD34471030 | [MOL File]
2101518-75-4.mol | [Molecular Weight]
509.51 |
| Hazard Information | Back Directory | [Uses]
PI3Kδ-IN-8 is a potent, selective and orally active PI3Kδ inhibitor, with an IC50 of 3.3 nM. PI3Kδ-IN-8 shows selectivity for PI3Kδ over PI3Kα, PI3Kβ, and PI3Kγ (IC50=377.2, 241.6, 17.9 nM, respectively). PI3Kδ-IN-8 has anti-tumor activity[1]. | [in vivo]
PI3Kδ-IN-8 (1-30 mg/kg; p.o. once daily for 24 d) significantly reduces the tumor volume and tumor weight in a dose-dependent manner in mice[1].
PI3Kδ-IN-8 (1 mg/kg; i.v.) displays a suitable half-life (1 h), Cmax (2.3 μM) and low clearance (5.6 mL/min/kg) in mice[1].
PI3Kδ-IN-8 (10 mg/kg; p.o.) displays moderate oral bioavailability (39%), Cmax (7.5 μM), and AUClast(22 μM?h) in mice[1]. | Animal Model: | Female NOD scid mice were injected OCI-Ly10 cells[1] | | Dosage: | 1, 3, 10, 30 mg/kg | | Administration: | P.o. once daily for 24 days | | Result: | Reduced the tumor volume, with an ED50 of 6.47 mg/kg.
Tumor growth inhibition of 81.95% was seen with a highly significant reduction in both tumor volume and tumor weight.
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| Animal Model: | Male BALB/c mice[1] | | Dosage: | 1 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis) | | Administration: | Intravenous administration and oral administration | | Result: | I.v.: t1/2=1 h, Cmax=2.3 μM, CL=5.6 mL/min/kg.
P.o.: F=39%, Cmax=7.5 μM, AUClast=22μM?h.
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| [IC 50]
PI3Kδ: 3.3 nM (IC50); PI3Kγ: 17.9 nM (IC50); PI3Kβ: 241.6 nM (IC50); PI3Kα: 377.2 nM (IC50) | [References]
[1] Shukla MR, et, al. Discovery of a Potent and Selective PI3Kδ Inhibitor (S)-2,4-Diamino-6-((1-(7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4H-quinolizin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile with Improved Pharmacokinetic Profile and Superior Efficacy in Hematological Cancer Models. J. Med. Chem. 2020 Dec 1. |
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