A8216-5mg | PP 2 (AG 1879) [172889-27-9] Clinisciences

Background

PP2 is a selective inhibitor of Src family with IC50 value of 4 nM and 5 nM for Lck and Fyn, respectively [1].

Src is a tyrosine kinase and contains 9 members: c-Src (this protein), Yes, Fyn, Fgr, Yrk, Lyn, Blk, Hck, and Lck [1].

PP2 is a potent Src family inhibitor that plays an important role in the cancer and is regarded as a promising target for treatment. When tested with human glioma cell line U251 spheroids in 3-D model, PP2 inhibited the cell invasion in a dose-dependent manner (2.5 μM, 10μM). And treated monolayer U251 cells with PP2 (10μM) decreased cell proliferation rate by inhibiting Src [2]. In human T cells, PP2 showed inhibition on anti-CD3-induced tyrosine phosphorylation by inhibiting Lck and Fyn that involved in the early T cell signal transduction [1].

In Sprague-Dawley rat model injected with urethane and after some needed treatment to perform research and record data, pretreatment with PP2 (50M, 10μL it) reversed the reflex potentiation, as well as Src kinase and NR2B phosphorylation by inhibiting Src family [3].

It is also reported that PP2 inhibits ZAP-70, JAK2 and EGF-R with IC50 value of >100 μM, >50 μM, and 480 nM, respectively [1].

References:
[1]. Hanke, J.H., et al., Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation. J Biol Chem, 1996. 271(2): p. 695-701.
[2]. Angers-Loustau, A., et al., SRC regulates actin dynamics and invasion of malignant glial cells in three dimensions. Mol Cancer Res, 2004. 2(11): p. 595-605.
[3]. Wu, H.C., et al., EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B. Am J Physiol Renal Physiol, 2011. 300(2): p. F403-11.

Product Citation

1. Zhang XH, Li CY, et al. "Pro-angiogenic activity of isoliquiritin on HUVECs in vitro and zebrafish in vivo through Raf/MEK signaling pathway." Life Sci. 2019 Apr 15;223:128-136. PMID:30876941

Chemical Properties

Physical Appearance	A solid
Storage	Desiccate at 4°C
M.Wt	301.78
Cas No.	172889-27-9
Formula	C₁₅H₁₆ClN₅
Solubility	insoluble in H2O; ≥15.1 mg/mL in DMSO; ≥20.05 mg/mL in EtOH with ultrasonic
Chemical Name	1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine
SDF	Download SDF
Canonical SMILES	CC(C)(C)N1C2=C(C(=N1)C3=CC=C(C=C3)Cl)C(=NC=N2)N
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	Human glioblastoma cell line U251
Preparation method	Soluble in DMSO > 15.1mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	10μmol/L, 4days for cell proliferation assays; 5μmol/L, 1min for fluorescent time-lapse videomicroscopy images
Applications	A decreased proliferation appeared in the glioma cell cultures treated with 10μmol/L PP2, suggesting thatinhibition of Src family kinase activity in glioma cells resulted in an exit from the cell cycle in monolayers. PP2 caused the disappearance of peripheral membrane ruffles within minutes.
Animal experiment [2]:
Animal models	Female Sprague-Dawley rats
Dosage form	50 μM, 10 μl, intrathecal injection
Application	Pretreatment with PP2 exhibited no effects on the TS(test stimulation)-evoked baseline reflex activity, it prevented ephrinB2-dependent reflex potentiation by decreasing the mean spike count evoked by the TS.
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]. Angers-Loustau A1, Hering R, et al, SRC regulates actin dynamics and invasion of malignant glial cells in three dimensions. Mol Cancer Res, 2004. 2(11): p. 595-605. [2]. Wu HC1, Chang CH, et al, EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B. Am J Physiol Renal Physiol, 2011. 300(2): p. F403-11.

Biological Activity

Description	PP2 is an inhibitor of Src family kinase.
Targets	LCK	Fyn	EGFR	JAK2	ZAP70
IC50	4 nM	5 nM	480 nM	>50 μM	>100 μM

Quality Control

Purity = 99.39%

Chemical structure

Related Biological Data

PP 2 (AG 1879) [172889-27-9]

Référence A8216-5mg

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