PP-121

PP121 is a multitargeted dual receptor tyrosine kinases inhibitor. PP121 blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases.

Product information

CAS Number: 1092788-83-4

Molecular Weight: 319.36

Formula: C17H17N7

Synonym:

PP121

PP 121

Chemical Name: 1-Cyclopentyl-3-(1H-pyrrolo[2, 3-b]pyridin-5-yl)-1H-pyrazolo[3, 4-d]pyrimidin-4-amine

Smiles: NC1=NC=NC2=C1C(=NN2C1CCCC1)C1C=C2C=CNC2=NC=1

InChiKey: NVRXTLZYXZNATH-UHFFFAOYSA-N

InChi: InChI=1S/C17H17N7/c18-15-13-14(11-7-10-5-6-19-16(10)20-8-11)23-24(12-3-1-2-4-12)17(13)22-9-21-15/h5-9,12H,1-4H2,(H,19,20)(H2,18,21,22)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 64 mg/mL(200.4 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

PP-121 selectivity interacts within a hydrophobic pocket that is conserved between both tyrosine kinases and PI3Ks, not serine-threonine kinases. PP-121 makes a hydrogen bond to Glu310 in Src, effectively substituting for the structural role of the catalytic lysine and resulting in the ordering of helix C and stabilization of an active conformation. PP-121 also inhibits other PI3Ks including p110α and DNA-PK with IC50 of 52 nM and 60 nM, respectively. PP-121 potently and dose-dependently blocks the phosphorylation of Akt, p70S6K and S6 in two glioblastoma cell lines, U87 and LN229. PP-121 potently inhibits the proliferation of a subset of the tumor cell lines by direct inhibition of PI3Ks and mTOR. PP-121 induces a G0/G1 arrest in LN220, U87 and Seg1 cells. PP-121 also blocks tyrosine phosphorylation induced by v-Src in NIH3T3 cells transformed with v-Src(Thr338). PP-121 could restore actin stress fiber staining in NIH3T3 cells transformed with v-Src(Thr338). PP-121 at a low concentration of 40 nM inhibits Ret autophosphorylation in TT thyroid carcinoma cells that express the C634W oncogenic Ret mutant35. PP-121 inhibits cell proliferation with IC50 of 50 nM in TT thyroid carcinoma cells. PP-121 inhibits cell proliferating stimulated only with VEGF with IC50 of 41 nM in human umbilical vein endothelial cells (HUVECs). PP-121 directly inhibits Bcr-Abl induced tyrosine phosphorylation, resulting in drug-induced apoptosis in K562 cells and a combination of apoptosis and cell cycle arrest in Bcr-Abl expressing BaF3 cells.

References:

1. Apsel B, et al. Nat Chem Biol, 2008, 4(11), 691-699.

Products are for research use only. Not for human use.