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Description:Duvelisib (formerly known as IPI-145 and INK1197, trade name: Copiktra), an isoquinolinone derivative, is a novel potent, orally bioactive and selective small-molecule phosphoinositide-3 kinases (PI3K) inhibitor with potential anticancer activity. It selectively and potently inhibits two PI3K isoforms, PI3K-δ and PI3K-γ, with IC50 of 2.5 nM and 27 nM respectively. In 2018, Duvelisib was approved by FDA to treat relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and follicular lymphoma.
References: Chem Biol. 2013 Nov 21;20(11):1364-74; Oncotarget. 2016 Jun 28;7(26):39784-39795.
Related CAS: 1261590-48-0 (R-isomer); 1386861-49-9 (hydrate)
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([[email protected]@H](NC3=C4N=CNC4=NC=N3)C)=CC5=C1C(Cl)=CC=C5
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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 ng•h/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.
Purity ≥98%
COA
MSDS
Targeting PI3K inhibits AML survival in AML cell lines and primary AML blasts.
IPI-145 inhibits AKT phosphorylation in AML. Oncotarget. 2016 Jun 28;7(26):39784-39795.
IPI-145 inhibits adhesion of AML blasts to primary BMSC. Oncotarget. 2016 Jun 28;7(26):39784-39795.