1092788-83-4 Usage
Description
1-Cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine, also known as PP-121, is a cell-permeable pyrazolopyrimidine compound that effectively targets the ATP pocket of both protein tyrosine kinases and PI 3-K family kinases. It is a multi-target inhibitor with potent inhibitory effects on various kinases, making it a promising candidate for therapeutic applications.
Uses
Used in Pharmaceutical Industry:
1-Cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is used as a multi-target kinase inhibitor for its potent inhibitory effects on various protein tyrosine kinases (e.g., Abl, EGFR, EphB4, Hck, PDGFR, RET, Src, SrcT338I, and VEGFR2) and PI 3-K family kinases (e.g., p110α/β/δ/γ, mTOR, and DNA-PK). Its ability to inhibit these kinases makes it a potential therapeutic agent for various diseases, particularly cancer.
Used in Cancer Treatment:
PP-121 is used as an anti-cancer agent due to its significant inhibition of multiple kinases involved in cancer cell proliferation and survival. It has been shown to be more effective than individual targeting of Ret by sorafenib or PI 3-K/mTOR pathway by PI-103 in inhibiting the proliferation of Ret C634W-expressing TT thyroid carcinoma cultures.
Used in Research Applications:
1-Cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is also used as a research tool in the study of kinase inhibition and its role in various cellular processes. Its potent inhibitory effects on a wide range of kinases make it a valuable compound for investigating the functions and interactions of these proteins in cellular signaling pathways.
Biological Activity
pp121 is a dual inhibitor of tyrosine and phosphoinositide kinases [1].pp121 is found to inhibit both tyrosine kinases and pi3-ks but not serine-threonine kinases. it potently inhibits p110α, p110β, p110γ, p110δ, dna-pk and mtor with ic50 values of 52nm, 1.4μm, 1.1μm, 150nm, 60nm and 10nm, respectively. for the tyrosine kinases, pp121 shows inhibition with ic50 values of 21nm, 4nm, 10nm,55nm, 550nm, 220nm and <1nm for ab1, hck, src, vegfr2, egfr, ephb4 and pdgfr, respectively [1].in cells, pp121 can reverse v-src mediated cellular transformation and restore actin stress fiber staining. pp121 also potently inhibits the mutant ret kinase with ic50 value less than 1nm in thyroid tumors34. furthermore, pp121 is found to evade drug resistance through redundantly targeting bcr-abl mediated cell survival and pi3-k/mtor mediated cell proliferation [1].
Biochem/physiol Actions
PP121 is a dual inhibitor of tyrosine and phosphoinositide kinases. PP121 is the first inhibitor active on both Tyrosine kinases and the phosphatidylinositol-3-OH kinase (PI(3)K) family. The inhibitor is not effecting other serine-threonine protein kinases.
references
[1] apsel b, blair j a, gonzalez b, et al. targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. nature chemical biology, 2008, 4(11): 691-699.
Check Digit Verification of cas no
The CAS Registry Mumber 1092788-83-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,9,2,7,8 and 8 respectively; the second part has 2 digits, 8 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 1092788-83:
(9*1)+(8*0)+(7*9)+(6*2)+(5*7)+(4*8)+(3*8)+(2*8)+(1*3)=194
194 % 10 = 4
So 1092788-83-4 is a valid CAS Registry Number.
1092788-83-4Relevant articles and documents
In-Cell Dual Drug Synthesis by Cancer-Targeting Palladium Catalysts
Clavadetscher, Jessica,Indrigo, Eugenio,Chankeshwara, Sunay V.,Lilienkampf, Annamaria,Bradley, Mark
, p. 6864 - 6868 (2017)
Transition metals have been successfully applied to catalyze non-natural chemical transformations within living cells, with the highly efficient labeling of subcellular components and the activation of prodrugs. In vivo applications, however, have been scarce, with a need for the specific cellular targeting of the active transition metals. Here, we show the design and application of cancer-targeting palladium catalysts, with their specific uptake in brain cancer (glioblastoma) cells, while maintaining their catalytic activity. In these cells, for the first time, two different anticancer agents were synthesized simultaneously intracellularly, by two totally different mechanisms (in situ synthesis and decaging), enhancing the therapeutic effect of the drugs. Tumor specificity of the catalysts together with their ability to perform simultaneous multiple bioorthogonal transformations will empower the application of in vivo transition metals for drug activation strategies.
Kinase antagonists
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Page/Page column 29; 52, (2008/06/13)
The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tryosine kinase, PI3Kinase and mTOR, or PI3Kinase, mTOR and tryosine kinase.
