CAS 1092788-83-4|PP121
Introduction：Basic information about CAS 1092788-83-4|PP121, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | PP121 | ||
|---|---|---|---|
| CAS Number | 1092788-83-4 | Molecular Weight | 319.364 |
| Density | 1.63 | Boiling Point | 650.9±50.0 °C at 760 mmHg |
| Molecular Formula | C17H17N7 | Melting Point | / |
| MSDS | ChineseUSA | Flash Point | 347.4±30.1 °C |
| Symbol | GHS07 | Signal Word | Warning |
Names
| Name | 1-cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-4-amine |
|---|---|
| Synonym | More Synonyms |
PP121 BiologicalActivity
| Description | PP121 is a multi-targeted kinase inhibitor with IC50s of 10, 60, 12, 14, 2 nM for mTOR, DNK-PK, VEGFR2, Src, PDGFR, respectively. |
|---|---|
| Related Catalog | Signaling Pathways >>Protein Tyrosine Kinase/RTK >>SrcResearch Areas >>Cancer |
| Target | mTOR:10 nM (IC50) PDGFR:2 nM (IC50) VEGFR2:12 nM (IC50) Src:14 nM (IC50) DNK-PK:60 nM (IC50) |
| In Vitro | PP121 blocks the PI3K pathway by direct inhibition of PI3K/mTOR in two glioblastoma cell lines, U87 and LN229. PP121 potently inhibits the proliferation of a diverse panel of tumor cell lines containing mutations in the PI3-K pathway components PIK3CA, PTEN, or RAS. PP121 induces a G0G1 arrest in most tumor cells. PP121 directly inhibits Src in cells and reverses its biochemical and morphological effects. PP121 potently inhibits the Ret kinase domain in vitro (IC50<1 nM). PP121 potently blocks VEGF stimulated activation of the PI3-K and MAPK pathways. PP121 inhibits VEGFR2 autophosphorylation at low nanomolar concentrations, confirming that this molecule directly targets VEGFR2 in cells. PP121 inhibits Bcr-Abl induced tyrosine phosphorylation in K562 cells as well as BaF3 cells that express Bcr-Abl[1]. |
| In Vivo | Oral administration of PP121 remarkably inhibits Eca-109 xenograft growth. Mice body weights are not significantly affected by PP121 or the vehicle treatment. PP121 oral administration dramatically inhibits activations of Akt-mTOR and NFkB in xenograft tumors. p-Akt Ser 473 and p-IKKa/b are both inhibited by PP121 administration[2]. |
| Kinase Assay | Purified kinase domains are incubated with inhibitors (PP121) at 2- or 4-fold dilutions over a concentration range of 50- 0.001 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[1]. |
| Cell Assay | Cells grown in 96-well plates are treated with PP121 at 4-fold dilutions (10 µM - 0.040 μM) or vehicle (0.1% DMSO). After 72 h cells are exposed to Resazurin sodium salt (22 µM) and fluorescence is quantified. IC50 values are calculated. For proliferation assays involving single cell counting, non-adherent cells are plated at low density (3–5% confluence) and treated with drug (2.5 µM) or vehicle (0.1% DMSO). Cells are diluted into trypan blue daily and viable cells counted using a hemocytometer[1]. |
| Animal Admin | Mice: Eca-109 cells are injected into the axillary regions of nude mice (5×106 cells/mouse). When the tumor volumes reach around 200 mm3, the mice are randomly separated to three groups: Untreated control, PP121 (30 mg/kg) and vehicle (10% 1-methyl-2-pyrrolidinone and 90% PEG 300) group. Tumor volumes and the mice body weights are measured every 10 d[2]. |
| References | [1]. Apsel B, et al. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol, 2008, 4(11), 691-699. [2]. Peng Y, et al. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121. Biochem Biophys Res Commun. 2015 Sep 11;465(1):137-44. |
Chemical & Physical Properties
| Density | 1.63 |
|---|---|
| Boiling Point | 650.9±50.0 °C at 760 mmHg |
| Molecular Formula | C17H17N7 |
| Molecular Weight | 319.364 |
| Flash Point | 347.4±30.1 °C |
| Exact Mass | 319.154541 |
| PSA | 98.30000 |
| LogP | 2.41 |
| Appearance of Characters | off-white |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.881 |
| InChIKey | NVRXTLZYXZNATH-UHFFFAOYSA-N |
| SMILES | Nc1ncnc2c1c(-c1cnc3[nH]ccc3c1)nn2C1CCCC1 |
| Storage condition | Store at +4°C |
| Water Solubility | DMSO: >10mg/mL |
Safety Information
| Symbol | GHS07 |
|---|---|
| Signal Word | Warning |
| Hazard Statements | H302 |
| Hazard Codes | Xn |
| Risk Phrases | 22 |
| RIDADR | UN 2811 6.1 / PGIII |
| Hazard Class | 22 |
Synonyms
| S2622_Selleck |
| PP-121,PP 121 |
| 1-cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine |
| KS1 |
| PP121 |
