A1720-1ml | Duvelisib (IPI-145, INK1197) [1201438-56-3] Biotrend

Background

IPI-145 (also known as INK1197), an isoquinolinone derivative, is a small-molecule phosphoinositide-3 kinases (PI3K) inhibitor that selectively and potently inhibits two PI3K isoforms, PI3K-δ and PI3K-γ, with half maximal inhibition concentration IC50 of 2.5 nM and 27 nM respectively. Despite of preference for PI3K-δ and PI3K-γ, IPI-145 also inhibits other PI3K isoforms, PI3K-α and PI3K-β, to a lesser extent with IC50 of 1602 nM and 85 nM respectively.

Due to the essential role of PI3K-δ in the proliferation of B cell and T cell, IPI-145 exhibits potent anti-proliferative activity against both cells with IC50 of 0.5 nM and 9.5 nM respectively leading to inhibition of neutrophil migration and basophil activation.

Inhibition of immune function through IPI-145-induced PI3K-δ and PI3K-γ blockade potentiates its application in the treatment of multiple inflammatory, autoimmune and hematologic diseases.

References:
[1] Winkler DG1, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM, Hoyt JG, Tillotson B, Murphy EL, Lim AR, Thomas BD, Macdougall JR, Ren P, Liu Y, Li LS, Jessen KA, Fritz CC, Dunbar JL, Porter JR, Rommel C, Palombella VJ, Changelian PS, Kutok JL. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74. doi: 10.1016/j.chembiol.2013.09.017. Epub 2013 Nov 7.

Product Citation

1. Yi Ouyang, Ziwei Ou, et al. "FGFR3 alterations in bladder cancer stimulate serine synthesis to induce immune-inert macrophages that suppress T-cell recruitment and activation." Cancer Res. 2023 Dec 15;83(24):4030-4046. PMID: 37768887

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	416.86
Cas No.	1201438-56-3
Formula	C₂₂H₁₇ClN₆O
Solubility	≥20.84 mg/mL in DMSO; insoluble in H2O; ≥24.9 mg/mL in EtOH
Chemical Name	(S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one
SDF	Download SDF
Canonical SMILES	O=C1N(C([C@H](C)NC2=C3N=CNC3=NC=N2)=CC4=C1C(Cl)=CC=C4)C5=CC=CC=C5
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1]:
Cell lines	Primary B cells and primary T cells
Preparation method	The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	IC50 value : 0.5 or 9.5 nM
Applications	IPI-145 showed potent anti-proliferative activity against both primary B cells and primary T cells, with IC50 values of 0.5 nM and 9.5 nM, respectively. Thus, it inhibited neutrophil migration and basophil activation.
Animal experiment [1]:
Animal models	Rats with previously established air pouches
Dosage form	1, 2.5, 5 and 10 mg/kg; p.o.
Applications	At the doses of 5 and 10 mg/kg, IPI-145 significantly inhibited neutrophil migration. More specifically, in the 10 mg/kg dose group, all animals showed significantly decreased neutrophil migration. In the 5 and 2.5 mg/kg dose groups, the results were more variable. The animals treated with 1 mg/kg IPI-145 showed little inhibition.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Winkler DG1, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM, Hoyt JG, Tillotson B, Murphy EL, Lim AR, Thomas BD, Macdougall JR, Ren P, Liu Y, Li LS, Jessen KA, Fritz CC, Dunbar JL, Porter JR, Rommel C, Palombella VJ, Changelian PS, Kutok JL. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.

Biological Activity

Description	IPI-145 is an orally bioavailable and highly selective inhibitor of PI3K-δ and PI3K-γ with IC50 values of 0.36 nM and 19.6 nM, respectively.
Targets	PI3K-δ	PI3K-γ
IC50	0.36 nM	19.6 nM

Quality Control

Purity = 99.55%

Duvelisib (IPI-145, INK1197) [1201438-56-3]

Cat# A1720-1ml

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Brand : APExBIO Technology