BI 2536

ArtNr	S1109-5
Hersteller	Selleckchem
CAS-Nr.	755038-02-9
Menge	5 mg
Quantity options	10 mg 100 mg 1 g 10 g 10 mM/1 mL 5 mg 50 mg 5 g
Kategorie	Oncology Food Safety Allergenes Inhibitors & Compound Libraries Small Molecules By Organ Skin Cancer Bladder Cancer Thyroid Cancer
Typ	Inhibitors
Specific against	other
Smiles	CCC1C(=O)N(C2=CN=C(N=C2N1C3CCCC3)NC4=C(C=C(C=C4)C(=O)NC5CCN(CC5)C)OC)C
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	755038-02-9'
Similar products	BI
Lieferbar
Manufacturer - Targets	PLK1
Storage Conditions	2 years -80 in solvent
Molecular Weight	521, 66
Administration	Injection i.v. once or twice per week
Animal Models	Female BomTac:NMRI-Foxn1nu mice injected subcutaneously with HCT 116, NCI-H460, or A549 cells
Cell lines	HeLa, A43, SKOV-3, HT-29, K562, A549, Saos-2, MCF7, HCT116, COLO 205, Hep G2, Raji and PC-3 cells, etc.
Clinical Trials	A Phase II study of BI 2536 infusional treatment in patients over 60 years of age with refractory or relapsed acute myeloid leukaemia has been completed.
Concentrations	Dissolved in DMSO, final concentrations ca.1 uM
Dosages	ca.50 mg/kg
Formulation	Formulated in hydrochloric acid (0.1 N), and diluted with 0.9% NaCl
IC50	0.83 nM [1], 0.83 nM [1], 0.83 nM [1], 0.83 nM [1], 0.83 nM [1], 0.83 nM [1]
In vitro	BI 2536 blocks the activities of Plk2 and Plk3 to a slightly lesser extent with IC50 of 3.5 nM and 9.0 nM, respectively. In HeLa cells, BI 2536 treatment ranging from 10-100 nM leads to the blocking of the recruitment of gamma-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, as well as a range of other mitotic processes that are known to depend on Plk1. BI 2536 treatment leads to the HeLa cells arrested in G2/M, subsequently a sub-G1 DNA peak indicative of DNA breakdown and apoptosis, and accumulated cleaved PARP p85 fragments in a concentration-dependent manner. BI 2536 inhibits the growth of a panel of 32 human cancer cell lines with EC50 of 2-25 nM, while blocking the proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells with EC50 of 12-31 nM. [1] Plk1 inhibition by BI 2536 reduces the growth and viability of anaplastic thyroid carcinoma (ATC) cells such as CAL62, OCUT-1, SW1736, 8505C, and ACT-1 with EC50 values of 1.4-5.6 nM. [2]
In vivo	BI 2536 given i.v. once or twice per week is highly efficacious in diverse xenograft models with acceptable tolerability by inhibiting cell proliferation through a mitotic arrest, and subsequently induction of tumor-cell death. Administration of BI 2536 at 50 mg/kg once or twice per week significantly inhibits growth of HCT 116 xenografts with T/C of 15% and 0.3%, respectively. BI 2536 treatment twice-weekly also leads to excellent tumor-growth in BxPC-3 and A549 models with T/C of 5% and 14%, respectively. [1]
Incubation Time	24 and 72 hours
Kinase Assay	Plk1 in vitro kinase assay, Recombinant human Plk1 (residues 1-603) is expressed as N-terminal, GST-tagged fusion protein with a baculoviral expression system and purified by affinity chromatography with Glutathione-agarose. Enzyme activity assays for Plk1 are performed in the presence of serially diluted BI 2536 with 20 ng of recombinant kinase and 10 ug casein from bovine milk as the substrate. Kinase reactions are performed in a final volume of 60 uL for 45 minutes at 30 C (15 mM MgCl2, 25 mM MOPS [pH 7.0], 1 mM DTT, 1% DMSO, 7.5 mM ATP, 0.3 uCi gamma-33P-ATP). Reactions are terminated by the addition of 125 uL of ice-cold 5% TCA. After transfer of the precipitates to Multi-Screen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curve is used for calculating IC50 value.
Method	Cells are exposed to various concentrations of BI 2536 for 24, and 72 hours. Cell growth is assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. For determining the DNA content of the cultures, cell suspensions are fixed in 80% ethanol, treated for 5 minutes with 0.25% Triton X-100 in PBS, and incubated with 0.1% RNase and 10 ug/mL propidium iodide (PI) in PBS for 20 minutes at RT. Cell-cycle profiles are determined by flow cytometric analysis.
Solubility (25C)	DMSO 96 mg/mL, Water <1 mg/mL, Ethanol 104 mg/mL
Information	BI-2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM in a cell-free assay. BI-2536 inhibits Bromodomain 4 (BRD4) with Kd of 37 nM and potently suppresses c-Myc expression. BI-2536 induces apoptosis and attenuates autophagy. Phase 2.
Chemical Name	(R)-4-(8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5, 6, 7, 8-tetrahydropteridin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide
Features	BI 2536 is the first potent and selective Plk1 inhibitor that induces all hallmarks of Plk1 inhibition.

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