Molecular Weight (MW)

416.86

Formula

C22H17ClN6O

CAS No.

1201438-56-3

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 83 mg/mL (199.1 mM)

Water:<1 mg/mL

Ethanol: <1 mg/mL

Solubility (In vivo)

30% PEG400+0.5% Tween80+5% Propylene glycol: 30mg/mL

Chemical Name

8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]isoquinolin-1-one

Synonyms

IPI145; IPI 145; IPI-145. INK1197; INK 1197; INK-1197; trade name: Copiktra

Other info

Chemical Name: (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one

InChi Key: SJVQHLPISAIATJ-ZDUSSCGKSA-N

InChi Code: InChI=1S/C22H17ClN6O/c1-13(28-21-19-20(25-11-24-19)26-12-27-21)17-10-14-6-5-9-16(23)18(14)22(30)29(17)15-7-3-2-4-8-15/h2-13H,1H3,(H2,24,25,26,27,28)/t13-/m0/s1

SMILES Code: O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4N=CNC4=NC=N3)C)=CC5=C1C(Cl)=CC=C5

In Vitro

In Vitro Assay: Duvelisib is a selectivite p100δ inhibitor with IC50 of 2.5 nM, 27.4 nM, 85 nM and 1602 nM for p110δ, P110γ, p110β and p110α, respectively. PI3Kδ and PI3Kγ inhibition with IPI-145 has anti-proliferative activity in primary AML cells by inhibiting the activity of AKT and MAPK. Pre-treatment of AML cells with IPI-145 inhibits both adhesion and migration of AML blasts to bone marrow stromal cells

Cell Assay: IPI-145 suppresses murine/human B-cell proliferation with EC50 of 0.5 nM/0.5 nM and also inhibits human T-cell proliferation with EC50 of 9.5 nM.

In Vivo

IPI-145 (10 mg/kg, p.o.) shows well pharmacokinetics with Cmax and AUC of 390 ng/mL and 137 ngoh/mL in mouse and rat. IPI-145 (10 mg/kg) is active in murine DTH model with ~50% ear swelling. IPI-145 (10 mg/kg) demonstrates dose-dependent effect in rat collagen induced arthritis (CIA) model. IPI-145 prevents inflammation and protects joint bone and cartilage in the rat CIA model. IPI-145 (10 mg/kg,QD) demonstrates activity in rat adjuvant induced polyarthritis model.

Animal model

Mouse and rat with collagen induced arthritis (CIA) model.

Formulation & Dosage

10 mg/kg, p.o.

References

Chem Biol. 2013 Nov 21;20(11):1364-74.