| Identification | Back Directory | [Name]
PP2 | [CAS]
172889-27-9 | [Synonyms]
PP2
CS-717
AG 1879
AGL 1879
PP2(AG 1879)
PP2(AGL 1879)
AG 1879,AGL 1879
PP2;AGL 1879;PP 2;PP-2
PP 2 (enzyme inhibitor)
Src kinase inhibitor PP2
PP 2;AG1879;AG 1879;AGL 1879
1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine
4-AMINO-5-(4-CHLOROPHENYL)-7-(T-BUTYL)PYRAZOLO[3,4-D]PYRIMIDINE
4-AMINO-5-(4-CHLOROPHENYL)-7-(TERT-BUTYL)PYRAZOLO[3,4-D]PYRIMIDINE
7-tert-butyl-5-(4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine
4-Amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine
[1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]amine
1-(TERT-BUTYL)-3-(4-CHLOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE
1-(TERT-BUTYL)-3-(4-CHLOROPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLAMINE
3-(4-CHLOROPHENYL) 1-(1,1-DIMETHYLETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE
1H-Pyrazolo[3,4-d]pyrimidin-4-amine, 3-(4-chlorophenyl)-1-(1,1-dimethylethyl)-
3-(4-Chlorophenyl)-1-(1,1-dimethylethyl)-(1H)-pyrazolo[3.4-d]pyrimidine-4-amine
3-(4-Chlorophenyl)-1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine AGL 1879 | [Molecular Formula]
C15H16ClN5 | [MDL Number]
MFCD01568210 | [MOL File]
172889-27-9.mol | [Molecular Weight]
301.77 |
| Chemical Properties | Back Directory | [Boiling point ]
493.5±40.0 °C(Predicted) | [density ]
1.35±0.1 g/cm3(Predicted) | [storage temp. ]
Desiccate at +4°C | [solubility ]
Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 3 mg/ml with warming). | [form ]
Off-white solid | [pka]
3.96±0.30(Predicted) | [color ]
Off-white | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month. |
| Hazard Information | Back Directory | [Description]
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 p56lck (IC50 = 4 nM), p59fynT (IC50 = 5 nM), Hck (IC50 = 5 nM), and Src (IC50 = 100 nM).1 PP2 does not significantly affect the activity of EGFR kinase (IC50 = 480 nM), JAK2 (IC50 > 50 μM), or ZAP-70 (IC50 > 100 μM).1 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.1 | [Uses]
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. | [Definition]
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. | [Biological Activity]
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). | [Biochem/physiol Actions]
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. | [Enzyme inhibitor]
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. | [storage]
Desiccate at 4°C | [References]
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 |
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