PP-121

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H17N7
Molecular Weight	319.3638
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C2C(=NN(C3CCCC3)C2=NC=N1)C4=CC5=C(NC=C5)N=C4

InChI

InChIKey=NVRXTLZYXZNATH-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26235881 | https://www.ncbi.nlm.nih.gov/pubmed/26056008

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. PP-121 is a multi-targeted inhibitor of PDGFR, Hck, mTOR, VEGFR2, Src and Abl with IC50 of 2 nM, 8 nM, 10 nM, 12 nM, 14 nM and 18 nM, also inhibits DNA-PK with IC50 of 60 nM. PP121 blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase receptor RET 14 Target ID: CHEMBL2041 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971	Inhibitor 8297
Mitogen-activated protein kinase kinase kinase 2 3 Target ID: CHEMBL5914 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26056008	Inhibitor 8297	30.0 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971	Inhibitor 8297	12.0 nM [IC50]
Tyrosine-protein kinase HCK 1 Target ID: CHEMBL3234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971	Inhibitor 8297	8.0 nM [IC50]
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971	Inhibitor 8297	13.0 nM [IC50]
Platelet-derived growth factor receptor 6 Target ID: CHEMBL2096980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971	Inhibitor 8297	2.0 nM [IC50]
Tyrosine-protein kinase SRC 19 Target ID: CHEMBL267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971	Inhibitor 8297	14.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18849971 https://www.ncbi.nlm.nih.gov/pubmed/26235881 https://www.ncbi.nlm.nih.gov/pubmed/24867098	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases.	2008 Nov	18849971
The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121.	2015 Sep 11	26235881

Patents

Sample Use Guides

In Vivo Use Guide

30 mg/kg, oral gavage, daily, 30 d

Route of Administration: Oral

In Vitro Use Guide

PP121 potently and dose-dependently (0.040 to 10 uM) blocked the phosphorylation of Akt, p70S6K and S6 in two glioblastoma cell lines, U87 and LN229. PP-121 at a low concentration of 40 nM inhibits Ret autophosphorylation in TT thyroid carcinoma cells that express the C634W oncogenic Ret mutant 35. 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).

Name

Type

Language

PP-121

Common Name

English

PP121

Code

English

1-CYCLOPENTYL-3-(1H-PYRROLO(2,3-B)PYRIDIN-5-YL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-4-AMINE

Systematic Name

English

1H-PYRAZOLO(3,4-D)PYRIMIDIN-4-AMINE, 1-CYCLOPENTYL-3-(1H-PYRROLO(2,3-B)PYRIDIN-5-YL)-

Systematic Name

English

Code System Code Type Description

CAS

1092788-83-4