172889-27-9

The Src family of non-receptor tyrosine kinases regulate cell adhesion, growth, and differentiation through activation of multiple intracellular signaling pathways. Normally inactive, Src kinases are transiently activated during mitosis and constitutively activated by abnormal mutations. PP2 is a potent, reversible, ATP-competitive, and selective inhibitor of the Src family of protein tyrosine kinases. It inhibits p56^lck (IC₅₀ = 4 nM), p59^fynT (IC₅₀ = 5 nM), Hck (IC₅₀ = 5 nM), and Src (IC₅₀ = 100 nM). PP2 does not significantly affect the activity of EGFR kinase (IC₅₀ = 480 nM), JAK2 (IC₅₀ > 50 μM), or ZAP-70 (IC₅₀ > 100 μM). PP2 inhibits the activation of focal adhesion kinase as well as its phosphorylation at Tyr⁵⁷⁷. PP2 also inhibits anti-CD3-stimulated tyrosine phosphorylation of human T-cells with an IC₅₀ value of 600 nM.

A potent and selective inhibitor of the Src family tyrosine kinases. Inhibits Lck (IC50=4 nM), Fyn (IC50=5 nM), and Hck (IC50=5 nM). It displays weaker inhibition of EGFR (IC50=480 nM) and no inhibition of ZAP-70 (IC50 100 μM) and JAK2 (IC5050 μM). PP2 is a useful tool for probing the involvement of Src family tyrosine kinases in cellular signaling.

ChEBI: PP2 is a member of the class of pyrazolopyrimidine that is pyrazolo[3,4-d]pyrimidin-4-amine bearing additional tert-butyl and 4-chlorophenyl substituents at positions 1 and 3 respectively. It is a potent ATP-competitive inhibitor of the Src family of protein tyrosine kinases. It has a role as an EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, a beta-adrenergic antagonist and a geroprotector. It is a pyrazolopyrimidine, an aromatic amine and a member of monochlorobenzenes.

Selective inhibitor of Src-family tyrosine kinases. Inhibits p56 lck and p59 fynT (IC 50 values are 4 and 5 nM respectively). Displays > 10000-fold selectivity over ZAP-70 and JAK2. Moderately inhibits CSK (IC 50 = 0.73 μ M).

PP2 is a selective inhibitor of Src-family tyrosine kinases of non-receptor tyrosine kinases (nRTK). It shows >10,000-fold selectivity over Zeta-chain-associated protein kinase 70 (ZAP-70) and Janus kinase 2 (JAK2). PP2 effectively reduces cervical cancer proliferation in vitro and in vivo.

This cell-permeable and photosensitive ATP site-directed pyrazole- pyrimidine (FW = 301.78 g/mol), also known as 4-amino-5- (4- chlorophenyl) -7- (t-butyl) pyrazolo[3,4-d]pyrimidine and tyrphostin AG 1879, potently inhibits Lck and Fyn protein kinases, with IC50 values of 4 nM and 5 nM. PP2 is ~100x less potent toward EGFR and is inactive for ZAP-70, JAK2 and PKA. PP2 prevented serum-independent growth of RET/PTC1-transformed NIH3T3 fibroblasts and of TPC1 and FB2, two human papillary thyroid carcinoma cell lines that carry spontaneous RET/PTC1 rearrangements. PP2 activates the E-cadherin-mediated cell adhesion system, suppressing metastasis in cancer cells. In cervical cancer cells (HeLa and SiHa), 10 μM PP2 down-regulates pSrc-Y416, pEGFR-Y845, and pEGFR-Y1173 expression levels, while down- regulatING pSrc-Y416 and pEGFR-Y845, but not pEGFR-Y1173. PP2 is also a potential neuroprotective agent in cerebral ischemia-reperfusion . Target (s) : casein kinase 1d, IC50 = 1.3 μM; Csk protein-tyrosine kinase; focal adhesion kinase; lymphocyte kinase, IC50 = 0.06 μM ; p56lck, IC50 = 4 nM; p59fynT, IC50 = 5 nM; receptor protein- tyrosine kinase; src protein-tyrosine kinase, IC50 = 0.7 μM (5,11,12- 23); stress-activated protein kinase 2a/p38, IC50 = 1.4 μM; and Yes kinase.

Desiccate at 4°C

1) Hanke et al. (1996), Discovery of a novel, potent and Src family-selective kinase inhibitor. Study of Lck-and FynT-dependent T cell activation; J. Biol. Chem., 271 695 2) Yoshizume et al. (2000), Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species; J. Biol. Chem., 275 11706