PP2

Catalog No.S7008 Synonyms: AG 1879,AGL 1879

For research use only.

PP2 (AG 1879, AGL 1879), a Src family kinase inhibitor, potently inhibits Lck/Fyn with IC50 of 4 nM/5 nM in cell-free assays, ~100-fold less potent to EGFR, inactive for ZAP-70, JAK2 and PKA.

PP2 Chemical Structure

CAS No. 172889-27-9

Selleck's PP2 has been cited by 93 publications

Purity & Quality Control

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Biological Activity

Description PP2 (AG 1879, AGL 1879), a Src family kinase inhibitor, potently inhibits Lck/Fyn with IC50 of 4 nM/5 nM in cell-free assays, ~100-fold less potent to EGFR, inactive for ZAP-70, JAK2 and PKA.
Targets
LCK [1]
(Cell-free assay)
Fyn [1]
(Cell-free assay)
4 nM 5 nM
In vitro

PP2 inhibits Src by binding to an area of the molecule that does not overlap with the ATP binding domain. [2] PP2 (20 μM) induces 40-50% growth inhibition of HT29 cells, this concentration reduces the Src activity as early as 1 hour and maintains a 35% inhibition of Src activity for 2 days. PP2 (100 mM) decreases the Src activity of HT29 cells in a dose-dependent manner. PP2 (1 mM-100 mM) causes a dose-dependent growth inhibition of human colon cancer cells (HT29, SW480, and PMCO1), liver cancer cells (PLC/PRF/5, KYN-2, Li7, and HepG2), and breast cancer cells (MCF-7, MDA-MB-468, and BT-474). PP2 (20 μM) significantly increases aggregation in most of the cancer cells (HT29, SW480, PMCO1, PLC/PRF/5, KYN-2, Li7, MCF-7, and MDA-MB-468) in E-cadherin dependent manner. PP2 (20 μM) enhances E-cadherin expression and also strongly increases E-cadherin’s association with the actin cytoskeleton in cancer cells. PP2 (20 μM) increases the expression of α-catenin, β-catenin, and γ-catenin in HT29 cells, whereas in PLC/PRF/5 and MCF-7 cells, the total protein level of α-catenin does not change, but the levels of β- catenin and γ-catenin increases slightly. [3] PP2 inhibits proliferation of two cervical cancer cells (HeLa and SiHa) in a time- and dose-dependent manner. PP2 (10 μM) down-regulates pSrc-Y416, pEGFR-Y845, and -Y1173 expression levels in HeLa and SiHa cells. PP2 (10 μM) could modulate cell cycle arrest by up-regulating p21(Cip1) and p27(Kip1) in both HeLa and SiHa cells and down-regulating expression of cyclin A, and cyclin dependent kinase-2, -4 (Cdk-2, -4) in HeLa and of cyclin B and Cdk-2 in SiHa. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A549 MVzHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M3PTVGdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGE2PDliY3XscJMtKEmFNUCgQUAxNjBzIN88UU4> MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDhzNEO3OEc,Ojh6MUSzO|Q9N2F-
T-cells NFr0cWFHfW6ldHnvckBie3OjeR?= NUTnbGVvUW6qaXLpeIlwdiCxZjDh[Ihme2mxbjDrbY5ie2ViaX6gbJVu[W5iVDDj[YxteyxiSVO1NEA:KDBwNjFOwG0v M2rIU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEe3N|Y{Lz5zOEC3O|M3OzxxYU6=
T-cells NFH3VoZHfW6ldHnvckBie3OjeR?= M1vse2lvcGmkaYTpc44hd2ZidInyc5NqdmVicHjvd5Bpd3K7bHH0bY9vKGmwIHj1cYFvKFRiY3XscJMtKEmFNUCgQUAxNjZizszNMi=> M3jzbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEe3N|Y{Lz5zOEC3O|M3OzxxYU6=
SH-SY5Y MWHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NVzT[mZoPzJiaILz NIHYVmRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPIMXN[PVliY3XscJMh[XO|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJkh[W[2ZYKgO|IhcHK|IHL5JHhVXCCjc4PhfUwhUUN3MDC9JFYvOSEQvF2u Moi2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6NU[xOVUoRjJzOEW2NVU2RC:jPh?=
Saos2 NHfQSWREgXSxdH;4bYNqfHliYYPzZZk> NFXqcpM1QCCqcoO= MmX4R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV4FwezJiY3XscJMh[W[2ZYKgOFghcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFgvODdizszNMi=> NVX1fZdQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5N|IxPzBpPkKzPVMzODdyPD;hQi=>
SaOS2 M1rXbWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M2LTZ2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU3HPV|Ih[2WubIOgZZN{\XO|ZXSgZZMh[2WubIXsZZIhfmmjYnnsbZR6NCCLQ{WwJF0hQC5zIN88UU4> M2rpRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5OUK5O|kzLz5zN{myPVc6OjxxYU6=
A431 M3XYW2Z2dmO2aX;uJIF{e2G7 Mn;uTY5pcWKrdH;yfUBm\m[nY4Sgc44heGixc4Doc{1UemNxbn;udIhwe3CqbzDh[pRmeiCHR1[gLFExOCC3TTmgd5RqdXWuYYTpc44hd2ZiQUSzNUBk\WyuczCoNlEqNCCLQ{WwJF0hOTdizszNMi=> M1G1NVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3MUC5OlQzLz5zNUGwPVY1OjxxYU6=
MEG01 NGLHd5pCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MV3BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2HR{CxJINmdGy|LDDJR|UxKD1iMUeg{txONg>? NHrERnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEK1O|UyOyd-MUiyOVc2OTN:L3G+
A431 M3XuemZ2dmO2aX;uJIF{e2G7 M1jie2lvcGmkaYTvdpkh\W[oZXP0JI9vKHCqb4PwbI8uW3KlIDjUfZI1OTZrIHHmeIVzKEWJRjCoNVAxKHWPKTDzeIlufWyjdHnvckBw\iCDNEOxJINmdGy|IDizPEktKEmFNUCgQUAzOiEQvF2u NVj4b5p6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUWxNFk3PDJpPkG1NVA6PjR{PD;hQi=>
K562 NHO4b5hCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NEDLbFVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFu1OlIh[2WubIOsJGlEPTBiPTCyOUDPxE1w M4TJdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MkW3OVE{Lz5zOEK1O|UyOzxxYU6=
A431 NHLRWXlCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= M3vXT3Rme3SnZDDmc5Ih[W62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBOFMyKGOnbHzzMEBKSzVyIE2gN|Ih|ryPLh?= MnP0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTVzMEm2OFIoRjF3MUC5OlQzRC:jPh?=
A431 NWLaOIxoSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NV7lbFl1SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBCPDNzIHPlcIx{NCCLQ{WwJF0hOzJwMjFOwG0v NYG2Sow2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[1NFk2PzNpPkG2OVA6PTd|PD;hQi=>
KU812 MUHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? Mn3uRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNVUixNkBk\WyuczygTWM2OCB;IES1JO69VS5? M{nkeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MkW3OVE{Lz5zOEK1O|UyOzxxYU6=
A431 NVXrVJBpTnWwY4Tpc44h[XO|YYm= MYixNEB2VQ>? MWDJcohq[mm2aX;uJI9nKFO{YzDheZRweGixc4Doc5J6dGG2aX;uJI9nKFl2MUmgbY4hSTR|MTDj[YxteyCjdDCxNEB2VQ>? MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjVyOUW3N{c,OTZ3MEm1O|M9N2F-
8701-BC NGq0TINRem:jcH;weI91cWNiYYPzZZk> Mon3NVAhfU1? M3;N[nBzd2Gyb4D0c5Rq[yCjY4Tpeol1gSCjZ3HpcpN1KDh5MEGtRmMh[2WubIOgZZQhOTBidV2gZpkhWEGUUDDhd5NigQ>? MoTMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ3MEm1O|MoRjF4NUC5OVc{RC:jPh?=
Assay
Methods Test Index PMID
Western blot p-PI3K / PI3K / p-AKT / AKT / Bcl-2 / Caspase-3 ; p-Src / Src / p-MAPK / MAPK 30250573 23704208
Immunofluorescence β-catenin ; FAK / p-FAK 18566211 17927818
In vivo PP2 (5 mg/kg/day) induces some slowing in the growth rate of the primary tumors relative to the control treated with vehicle in SCID mice inoculated HT29 cells in the spleen. PP2 (5 mg/kg/day) induces some slowing in the growth rate of the primary tumors relative to the control treated with vehicle in SCID mice inoculated HT29 cells in the spleen. PP2 (5 mg/kg/day) significantly reduces the relative liver weight and liver metastasis volume compared with the controls in SCID mice inoculated HT29 cells in the spleen. [3] PP2 (1.5 mg/kg i.p.) treated rats show approximately 50% reduction of infarct size on T2-weighted MRI and in TTC staining compared with controls in rats with focal ischemic brain injury. PP2 (1.5 mg/kg i.p.) results in better the neurological score than controls in rats with focal ischemic brain injury. [5]

Protocol (from reference)

Kinase Assay:[1]
  • Immune complex enzyme assays:

    The acid-treated enolase is diluted 1:20 with 1× PBS before aliquoting 100 mL/well into a Nunc 96-well high protein binding assay plate. Assay wells are then aspirated; blocked with 0.5% bovine serum, 1× PBS for 1 h at 37 ℃;and then washed five times with 300 mL of 1× PBS/well. The source of Lck is either LSTRA cells or Lck expressed in HeLa cells using a vaccinia expression system. FynT is expressed in HeLa cells using the vaccinia system. Cells (12.5× 106/mL) are lysed in lysis buffer (20 mM Tris, pH 8.0, 150 mM NaCl, 0.5% Nonidet P-40, and 23 trypsin inhibitory units/mL aprotinin), and the lysates are clarified by centrifugation at 14,000 cpm for 15 min at 4 ℃ in an Eppendorf tube. The clarified lysates are then incubated with the appropriate anti-kinase antibody at 10 μg/mL for 2 h at 4 ℃. Protein A-Sepharose beads are added to the antibody/lysate mixture at 250 μL/mL and allowed to incubate for 30 min at 4 ℃. The beads are then washed twice in 1 mL of lysis buffer and twice in 1 mL of kinase buffer (25 mM HEPES, 3 mM MnCl2, 5mM MgCl2, and 100 μM sodium orthovanadate) and resuspended to 50% (w/v) in kinase buffer. Twenty-five microliters of the bead suspension is added to each well of the enolase-coated 96-well high protein binding plate together with an appropriate concentration of compound and [γ-32P]ATP (25 μL/well of a 200 μCi/mL solution in kinase buffer). After incubation for 20 min at 20 ℃, 60 μLl of boiling 2× solubilization buffer containing 10 mM ATP is added to the assay wells to terminate the reactions. Thirty microliters of the samples is removed from the wells, boiled for 5 min, and run on a 7.5% SDS-polyacrylamide gel. The gels are subsequently dried and exposed to Kodak X-AR film. For quantitation, films are scanned using a Molecular Dynamics laser scanner, and the optical density of the major substrate band, enolase p46, is determined. In companion experiments for measuring the activity of compounds against Lck, the assay plate is washed with two wash cycles on a Skatron harvester using 50 mM EDTA, 1 mM ATP. Scintillation fluid (100 μL) is then added to the wells, and 32P incorporation is measured using a micro-β-counter.

Cell Research:[3]
  • Cell lines: HT29, SW480, PMCO1, PLC/PRF/5, KYN-2, Li7, HepG2, MCF-7, MDA-MB-468 and BT-474 cell lines
  • Concentrations: ~100 μM
  • Incubation Time: 2 days
  • Method: Cell viability is determined using an in vitro toxicology assay kit following the manufacturer’s instructions. Cells are seeded in 96-well plates at day 0. Starting at day 1, cells are treated for 2 days with each of a series of increasing concentrations of PP2 (1 μM, 10 μM, and 100 μM). At the end of this period, cell proliferation is evaluated by a colorimetric assay based on the cleavage of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide by mitochondria dehydrogenase in viable cells, leading to formazan formation. This experiment is repeated three times with 10 determinations/tested concentration.
  • (Only for Reference)
Animal Research:[3]
  • Animal Models: SCID mice inoculated HT29 cells in the spleen
  • Dosages: 5 mg/kg/day
  • Administration: intraperitoneal injection
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 60 mg/mL
(198.82 mM)
Ethanol 2 mg/mL
(6.62 mM)
Water Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
4% DMSO+corn oil
For best results, use promptly after mixing.

2.5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 301.77
Formula

C15H16ClN5

CAS No. 172889-27-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)(C)N1C2=NC=NC(=C2C(=N1)C3=CC=C(C=C3)Cl)N

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03842371 Not yet recruiting Other: Metabolic level of BCAAs in monocytes and macrophages Sepsis Syndrome West China Hospital February 11 2019 --
NCT02407626 Terminated Drug: Propofol|Drug: Sevoflurane Myocardial Ischemia Triemli Hospital|University of Alberta September 2015 Not Applicable
NCT02315287 Recruiting Drug: Pioglitazone|Drug: Lobeglitazone Type 2 Diabetes Seoul National University Bundang Hospital September 2014 Phase 4

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

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

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Frequently Asked Questions

Question 1:
Could you please suggest me the in vivo details about the dilution to reduce the amount of DMSO to 1 to 5%?

Answer:
For in vivo study, we recommend to use 4% DMSO +Corn oil up to 2.5 mg/ml.

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