Product Categories

PP-121

PP-121 is a multi-target 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, respectively, and also inhibits DNA-PK with IC50 of 60 nM.

Catalog No.S2622

1 Reviews

: Tel: +1-832-582-8158[email protected]

PP-121 Chemical Structure
Molecular Weight: 319.36

Validation & Quality Control

Customer Reviews(1) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

PP-121 is available in the following compound libraries:

Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well)

Product Information

Compare PDGFR Inhibitors

Research Area
Research Area
PP-121 Mechanism
PP-121 Mechanism
Src kinases contains a conserved domain structure consisting of consecutive SH3 (binding the linker segment between the SH2 and kinase domain), SH2 (phosphotyrosine recognition), and SH1 (tyrosine kinase) domains. Besides, Src also contains a 'unique' membrane-targeting domain (SH4) at their N-terminus. In particular, the kinase domain consists of N-terminal small lobe and C-terminal large lobe is composed of five -strands and a single -helix, termed the C helix, the former is involved in the regulatory mechanism deployed in Src kinases, while the latter contains the regulatory activation loop, which is the site of activating tyrosine phosphorylation in Src and other kinases. Nucleotide binding and phosphotransfer occur in the cleft between the two lobes. ^[1]
The crystal structure indicates that PP-121 binds in the active site of c-Src. Specifically, the pyrazolopyrimidine core is anchored to the hinge region via two hydrogen bonds from N4 and N5 to the backbone of Tyr340 and Met431, respectively. Besides, N4 of pyrazolopyrimidine core also forms another H-bond to the gatekeeper (Thr338). The R1 aryl substituent of PP-121 extends into a hydrophobic pocket and forms a hydrogen bond with the conserved Glu310, which organizes the active site for catalysis by interacting with the catalytic Lys295. Thus, the binding mode improves the affinity between PP-121 and Src, and inhibits the activation of Src. ^[2]
References
[1] Boggon TJ, et al. Oncogene. 2004, 23(48), 7918-7927.
[2] Apsel B, et al. Nat Chem Biol. 2008, 4(11), 691-699.
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1040	Sorafenib (Nexavar)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1042	Sunitinib Malate (Sutent)	<1 mg/mL	15 mg/mL	<<1 mg/mL
S1490	Ponatinib (AP24534)	<1 mg/mL	30 mg/mL	<1 mg/mL
S1026	Imatinib Mesylate	118 mg/mL	118 mg/mL	<1 mg/mL
S2475	Imatinib (Gleevec)	<1 mg/mL	3 mg/mL	<1 mg/mL
S1010	BIBF1120 (Vargatef)	<1 mg/mL	6 mg/mL	3 mg/mL
S1035	Pazopanib HCl	<1 mg/mL	17 mg/mL	<1 mg/mL
S1005	Axitinib	<1 mg/mL	1 mg/mL	<1 mg/mL
S2730	Crenolanib (CP-868596)	<1 mg/mL	89 mg/mL	7 mg/mL
S1018	Dovitinib (TKI-258)	<1 mg/mL	30 mg/mL	<1 mg/mL
S1207	Tivozanib (AV-951)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1470	TSU-68 (SU6668)	<1 mg/mL	62 mg/mL	<1 mg/mL
S1064	Masitinib (AB1010)	<1 mg/mL	100 mg/mL	4 mg/mL
S1536	CP 673451	<1 mg/mL	42 mg/mL	4 mg/mL
S1003	Linifanib (ABT-869)	<1 mg/mL	75 mg/mL	<1 mg/mL
S1244	Amuvatinib (MP-470)	<1 mg/mL	32 mg/mL	<1 mg/mL
S2774	MK-2461	<1 mg/mL	99 mg/mL	<1 mg/mL
S1032	Motesanib Diphosphate (AMG-706)	114 mg/mL	114 mg/mL	<1 mg/mL
S2769	Dovitinib Dilactic acid (TKI258 Dilactic acid)	70 mg/mL	90 mg/mL	<1 mg/mL
S1363	Ki8751	<1 mg/mL	47 mg/mL	<1 mg/mL
S2231	Telatinib (BAY 57-9352)	<1 mg/mL	82 mg/mL	1 mg/mL
S2622	PP-121	<1 mg/mL	64 mg/mL	2 mg/mL
S1557	KRN 633	<1 mg/mL	9 mg/mL	<1 mg/mL
S8024	Tyrphostin AG 1296 (AG 1296)	<1 mg/mL	6 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Tech Support & FAQs

Biological Activity

Description	PP-121 is a multi-target 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, respectively, and also inhibits DNA-PK with IC50 of 60 nM.
Targets	PDGFR	Hck	mTOR	VEGFR2	Src	Abl
IC50	2 nM	8 nM	10 nM	12 nM	14 nM	18 nM ^[1]
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. ^[1]
In vivo
Clinical Trials
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

Kinase assays	Purified kinase domains are incubated with PP-121 at 2- or 4-fold dilutions over a concentration range of 1nM-50 µM or with vehicle (0.1% DMSO) in the presence of 10 µM ATP, 2.5 µCi of γ-³²P-ATP and substrate. Reactions are terminated by spotting onto nitrocellulose or phosphocellulose membranes, depending on the substrate; this membrane is then washed 5–6 times to remove unbound radioactivity and dried. Transferred radioactivity is quantitated by phosphorimaging and IC50 values are calculated by fitting the data to a sigmoidal doseresponse using Prism software.

Kinase assays

Purified kinase domains are incubated with PP-121 at 2- or 4-fold dilutions over a concentration range of 1nM-50 µM or with vehicle (0.1% DMSO) in the presence of 10 µM ATP, 2.5 µCi of γ-³²P-ATP and substrate. Reactions are terminated by spotting onto nitrocellulose or phosphocellulose membranes, depending on the substrate; this membrane is then washed 5–6 times to remove unbound radioactivity and dried. Transferred radioactivity is quantitated by phosphorimaging and IC50 values are calculated by fitting the data to a sigmoidal doseresponse using Prism software.

Cell Assay: ^[1]

Cell lines	U87, LN229, NIH3T3, HUVECs, BaF3 and TT thyroid carcinoma cells
Concentrations	0.04-20 μM
Incubation Time	24-72 hours
Method	For western blot analysis, cells are grown in 12-well plates and treated with PP-121 at the indicated concentrations or vehicle (0.1% DMSO). Treated cells are lysed, lysates are resolved by SDS-PAGE, transferred to nitrocellulose and blotted. For cell proliferation assays,cells are grown in 96-well plates are treated with PP-121 at 4-fold dilutions (10 µM - 0.040 μM) or vehicle (0.1% DMSO). After 72 hours cells are exposed to Resazurin sodium salt (22 µM) and fluorescence is quantified. IC50 values are calculated using Prism software. For proliferation assays involving single cell counting, non-adherent cells are plated at low density (3–5% confluence) and treated with PP-121 (2.5 µM) or vehicle (0.1% DMSO). Cells are diluted into trypan blue daily and viable cells counted using a hemocytometer. For apoptosis and cell cycle analysis, cells are treated with the indicated concentration of PP-121 or vehicle (0.1% DMSO) for 24–72 hours. Cells are either stained live with AnnexinV-FITC or fixed with ethanol and stained with propidium iodide. Cell populations are separated using a FacsCalibur flow cytometer; data is collected using CellQuest Pro software and analyzed with either ModFit or FlowJo Software.

References

Chemical Information

Download PP-121 SDF

Molecular Weight (MW)	319.36
Formula	C₁₇H₁₇N₇
CAS No.	1092788-83-4
Synonyms	N/A

Solubility (25°C) DMSO 64 mg/mL Water <1 mg/mL Ethanol 2 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

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

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Customer Reviews (1)

Click to enlarge

Rating

Source

Dr. Zhang of Tianjin Medical University. PP-121 purchased from Selleck

Method

Western blot

Cell Lines

A549 cells

Concentrations

0-10 μM

Incubation Time

3 h

Results

PP-121 treatment resulted in a reduction of AKT phosphorylation in A549 cells.

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3Monday–Friday 9:00 AM–5:00 PM (Central Time)

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related PDGFR Inhibitors

Linifanib (ABT-869)

Linifanib (ABT-869) is a novel, potent ATP-competitive RTK inhibitor for KDR, CSF-1R, Flt-1, Flt-3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM, 3 nM, and 66 nM respectively.
BEZ235 (NVP-BEZ235)

BEZ235 (NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor of p110α, p110γ, p110δ and p110β with IC50 of 4 nM, 5 nM, 7 nM and 75 nM, respectively, and also inhibits ATR with IC50 of 21 nM.
BIBF1120 (Vargatef)

BIBF1120 (Vargatef) is a potent inhibitor of VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.
Dovitinib (TKI-258)

Dovitinib (TKI258, CHIR258) is a novel multi-target inhibitor for Flt3, c-Kit, FGFR1/3, VEGFR1/2/3, PDGFRα/β with IC50 of 1 nM, 2 nM, 8 nM/9 nM and 10 nM/13 nM/8 nM, 210 nM/27 nM respectively.
Deforolimus (Ridaforolimus)

Deforolimus (Ridaforolimus, AP23573, MK-8669) is a selective mTOR inhibitor with IC50 of 0.2 nM.
Motesanib Diphosphate (AMG-706)
Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3, PDGFR, c-Kit and Ret with IC50 of 2 nM/3 nM/6 nM, 84 nM, 8 nM and 59 nM, respectively.
PI-103

PI-103 is a potent, ATP-competitive PI3K inhibitor of DNA-PK, p110α, mTORC1, PI3KC2β, p110δ, mTORC2, p110β, and p110γ with IC50 of 2 nM, 8 nM, 20 nM, 26 nM, 48 nM, 83 nM, 88 nM and 150 nM, respectively.
Masitinib (AB1010)
Masitinib is a novel tyrosine kinases inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, resectively.
PIK-75

PIK-75 is a selective and competitive inhibitor of p110α with IC50 of 5.8 nM and also potently inhibits DNA-PK with IC50 of 2 nM.
Tivozanib (AV-951)
AV-951 (Tivozanib, KRN-951) is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 0.21 nM/0.16 nM/0.24 nM and also inhibits PDGFR and c-Kit with IC50 of 1.72 nM and 1.63 nM, respectively.

RTKs and Angiogenesis Related Products

> Download

Choose Your Country or Region

Product Categories

PP-121