« Back
Home /
PHA-680632

PHA-680632

Item no.	S1454-10000
Manufacturer	Selleckchem
CASRN	398493-79-3
Amount	10 g
Quantity options	10 mg 1 g 10 g 10 mM/1 ml 200 mg 5 mg 50 mg 5 g
Category	Oncology Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Bladder Cancer Colorectal Cancer Breast Cancer Testicular & Prostate Cancer
Type	Inhibitors
Specific against	other
Smiles	CCC1=C(C(=CC=C1)CC)NC(=O)N2CC3=C(C2)NN=C3NC(=O)C4=CC=C(C=C4)N5CCN(CC5)C
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	Aurora A,Aurora B,Aurora C,Aurora Kinase
Similar products	PHA-680632
Available
Storage Conditions	2 years -80 in solvent
Molecular Weight	501, 62
Administration	Intraperitoneal (i.p.) injection twice a day
Animal Models	Mice (female athymic nude) xenografts models of p53 / HCT116 cells
Cell lines	HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells
Concentrations	0.001-1 uM, dissolved in DMSO as 10 mM stock solution
Dosages	40 mg/kg
Formulation	Dissolved in 20% Tween-80 in 5% glucose solution
IC50	27 nM, 27 nM, 27 nM, 27 nM, 27 nM, 27 nM
In vitro	PHA-680632 potently inhibits all three Aurora kinases (A, B, and C) with IC50 values of 27, 135, and 120 nM, respectively. PHA-680632 is selective for Aurora kinases, with 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, VEGFR2, and VEGFR3, and with IC50 higher than 10 uM for another 22 kinases. PHA-680632 shows potent anti-proliferative effects in a wide range of cell types with IC50 values of 0.06â€“7.15 uM, including HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells. PHA-680632 (0.5 uM) causes polyploidy in tumor cells. The mechanism of action of PHA-680632 is in agreement with inhibition of Aurora kinases. [1] PHA680632 in association with radiation leads to additive effects in cancer cells, especially in the p53-deficient cells. Combined ionising radiation (IR) and treatment of PHA680632 (100â€“400 nM) prior to IR leads to an enhancement of radiation-induced Annexin V positive cells, micronuclei formation, and Brca1 foci formation only in HCT116 cells with deficient p53, other than the p53 wtype counterparts. [2]
In vivo	HA-680632 (15â€“60 mg/kg) inhibits tumor growth in mice xenografts models of HL60, A2780, and HCT116 cells, by reducing tumor cell proliferation and increasing apoptosis. PHA-680632 (45 mg/kg) suppresses growth of activated ras-driven mammary tumors in mouse mammary tumor virus v-Ha-ras transgenic mice and results in complete tumor stabilization and partial regression. [1]
Incubation Time	72 hours
Kinase Assay	Aurora Kinase Inhibition Assay, Inhibition of kinase activity by PHA-680632 is assessed using a scintillation proximity assay format. The biotinylated substrate is transphosphorylated by the kinase in presence of ATP traced with gamma33-ATP. The phosphorylated substrate is then captured using streptavidin-coated scintillation proximity assay beads and the extent of phosphorylation is evaluated by beta-counter after a 4-hour rest for the floatation of the beads on a dense 5 M CsCl solution. In particular, a peptide derived from the Chocktide sequence (LRRWSLGL) is used as substrate for Aurora A, whereas the optimized peptide Auroratide is employed for Aurora B and C. The assay is run in a robotized format on 96-well plates. The potency of the compound toward Aurora kinases is evaluated and IC50 values are determined.
Method	Cells (5x103 to 1.5x104 per cm2) are seeded in 24-well plate. After 24 hours, plates are treated with PHA-680632 and incubated for 72 hours. At the end of incubation time, cells are detached from each plate and counted using a cell counter. IC50s are calculated using percentage of growth versus untreated control.
Solubility (25C)	DMSO 100 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	PHA-680632 is a potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3.
Chemical Name	N-(2, 6-diethylphenyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)pyrrolo[3, 4-c]pyrazole-5(1H, 4H, 6H)-carboxamide

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Request Data Sheet

S1454-10000-datasheet.pdf

S1454-10000-safety-datasheet.pdf