ChemicalBook CAS DataBase List 2101518-75-4

2101518-75-4

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
Molecular Formula	C28H21F2N7O
MDL Number	MFCD34471030
Molecular Weight	509.51
MOL File	2101518-75-4.mol

Chemical Properties

Boiling point	871.0±75.0 °C(Predicted)
density	1.47±0.1 g/cm3(Predicted)
pka	3.80±0.50(Predicted)

Hazard Information

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), C_max (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%), C_max (7.5 μM), and AUC_last(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.

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.: t_1/2=1 h, C_max=2.3 μM, CL=5.6 mL/min/kg. P.o.: F=39%, C_max=7.5 μM, AUC_last=22μM?h.

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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