172889-27-9 Usage
Uses
Used in Pharmaceutical Research:
1-tert-butyl-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is used as a research compound for studying the effects of Src/focal adhesion kinase (FAK) signaling on IQ domain GTPase-activating protein 1 (IQGAP1)-mediated anoikis resistance. This application is crucial for understanding the molecular mechanisms underlying cell adhesion and survival, which are essential for the development of targeted therapies against various diseases, including cancer.
Used in Cancer Research:
In the field of cancer research, 1-tert-butyl-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is used for Src inhibition to study its effect on epidermal growth factor receptor (EGFR) and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation in non-small cell lung cancer (NSCLC) cells. This research is vital for developing novel therapeutic strategies against lung cancer by targeting specific signaling pathways involved in tumor progression and resistance to treatment.
Used in Breast Cancer Research:
1-tert-butyl-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is also utilized in the study of pharmacological inhibition of SRC in MDA-MB-231 breast cancer cells. This application aims to investigate the role of Src kinase in breast cancer cell proliferation, survival, and metastasis, providing insights into the development of targeted therapies for breast cancer patients.
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 pyrazolepyrimidine (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 downregulatING 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 proteintyrosine 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.
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
Check Digit Verification of cas no
The CAS Registry Mumber 172889-27-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,7,2,8,8 and 9 respectively; the second part has 2 digits, 2 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 172889-27:
(8*1)+(7*7)+(6*2)+(5*8)+(4*8)+(3*9)+(2*2)+(1*7)=179
179 % 10 = 9
So 172889-27-9 is a valid CAS Registry Number.
InChI:InChI=1/C15H16ClN5/c1-15(2,3)21-14-11(13(17)18-8-19-14)12(20-21)9-4-6-10(16)7-5-9/h4-8H,1-3H3,(H2,17,18,19)
172889-27-9Relevant academic research and scientific papers
Todorovic, Nick,Awuah, Emelia,Shakya, Tushar,Wright, Gerard D.,Capretta, Alfredo
, p. 5761 - 5763 (2011)
The parallel synthesis of a library N1- and C3-substituted-pyrazolo[3,4-d] pyrimidines is described. The microwave-assisted approach involves the de novo generation of the heterocyclic scaffold, facile alkylation at N1 via either a Mitsunobu or a direct alkylation reaction and arylation at C3 via a Suzuki reaction.
