755038-02-9

Basic information

• Product Name: BI 2536
• Synonyms: BI 2536;BI-2536, BoehringerPLK-1 inhibitor;4-[[(7R)-8-Cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)benzamide;Benzamide, 4-[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-;Boehringer PLK-1 inhibitor;BI-2536(R-);BI2536/BI-2536;(R)-4-((8-cyclopentyl-7-ethyl-5-Methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)aMino)-3-Methoxy-N-(1-Methylpiperidin-4-yl)benzaMide
• CAS NO: 755038-02-9
• Molecular Formula: C₂₈H₃₉N₇O₃
• Molecular Weight: 521.662
• EINECS: 1308068-626-2
• Product Categories: API;Inhibitors
• Mol File: 755038-02-9.mol
• Article Data: 11

Chemical Properties

• Appearance: /
• Density: 1.28
• Storage Temp.: Keep in dark place,Sealed in dry,Store in freezer, under -20°C
• Solubility: Soluble in DMSO (up to 20 mg/ml) or in Ethanol (up to 25 mg/ml)
• PKA: 14.09±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: BI 2536(CAS DataBase Reference)
• NIST Chemistry Reference: BI 2536(755038-02-9)
• EPA Substance Registry System: BI 2536(755038-02-9)

Safety Data

• Hazardous Substances Data: 755038-02-9(Hazardous Substances Data)

Usage

Description

BI 2536 (755038-02-9) was originally reported as a potent (IC50’s Plk1 = 0.83nM, Plk2 = 3.5nM and Plk3 = 9.0nM)1?and selective2?Polo-like kinase inhibitor?that caused mitotic arrest and apoptosis induction in various human cancer cell lines.1?It was later found to be a potent inhibitor (IC50?= 100nM) of BET family member BRD4 and able to potently suppress c-Myc expression in MM.1S multiple myeloma cells.3?BI 2536 destabilizes N-Myc by inhibiting the deactivation of the ubiquitin E3 ligase Fbw7 by Plk1.4

Uses

BI 2536 is a PLK1 inhibitor, inducing apoptosis together with micro-tubule-destabilizing drugs in preclinical rhabdomyosarcoma models. Anti-cancer and potent PLK1 inhibitor.

References

1) Steegmaier?et al.?(2007),?BI 2536, a Potent and Selective Inhibitor of Polo-like Kinase 1, Inhibits Tumor Growth In Vivo; Curr. Biol.,?17?316 2) Davis?et al.?(2011),?Comprehensive analysis of kinase inhibitor selectivity; Nat. Biotechnol.,?29?1046 3) Ciceri?et al.?(2014),?Dual kinase-bromodomain inhibitors for rationally designed polypharmacology; Nat. Chem. Biol.,?10?305 4) Xiao?et al.?(2016),?Polo-like Kinase-1 Regulates Myc Stabilization and Activates a Feedforward Circuit Promoting Tumor Cell Survival; Mol. Cell,?64?493

Upstream product

• 41838-46-4 4-Amino-1-methylpiperidine 
• 755039-56-6 (R)-4-((8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-methoxybenzoic acid 
• 755039-53-3 (R)-methyl 2-((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)-amino)butanoate 
• 755039-54-4 (R)-2-chloro-8-cyclopentyl-7-ethyl-7,8-dihydropteridin-6(5H)-one 
• 755039-55-5 (R)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one 
• 755039-52-2 (R)-methyl 2-(cyclopentylamino)butanoate 
• 876126-59-9 3-methoxy-N-(1-methylpiperidin-4-yl)-4-nitrobenzamide 
• 5081-36-7 3-methoxy-4-nitrobenzoic acid 
• 876126-60-2 4-amino-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide 

Downstream Products

• 876126-71-5 4-[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide; monohydrate 

Relevant articles and documents

Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors

The simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase-bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.

Bioorthogonal probes for polo-like kinase 1 imaging and quantification

Click inside: A nuclear protein target, polo-like kinase 1 (PLK1) was imaged using a biocompatible bioorthogonal ligation between a specific drug and a fluorescent dye in live cells (see picture). Colocalization of the dye and the protein target was confi

Process for the manufacture of dihydropteridinones

Disclosed are processes for preparing dihydropteridinones of general formula (I) wherein the groups L and R1-R5 have the meanings given in the claims and in the specification.