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

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

Uses

Used in Anticancer Applications:
BI 2536 is used as an anti-cancer agent for its ability to induce apoptosis in combination with micro-tubule-destabilizing drugs in preclinical rhabdomyosarcoma models. It targets and inhibits Polo-like kinases (PLK1, PLK2, and PLK3), which play a crucial role in cell division and are often overexpressed in cancer cells, leading to uncontrolled cell proliferation and tumor growth.
Used in Drug Delivery Systems:
While the provided materials do not specifically mention drug delivery systems for BI 2536, it can be inferred that novel drug delivery systems could be developed to enhance the bioavailability, delivery, and therapeutic outcomes of BI 2536 in cancer treatment. These systems may include organic and metallic nanoparticles as carriers, similar to those used for other anticancer agents.
Used in Pharmaceutical Research:
BI 2536 is used as a potent PLK1 inhibitor in pharmaceutical research for the development of new cancer treatments. Its ability to induce mitotic arrest and apoptosis in cancer cells makes it a valuable compound for studying the mechanisms of cancer cell death and the potential for targeted cancer therapies.
Used in Multiple Myeloma Treatment:
BI 2536 is used as a therapeutic agent for multiple myeloma, a type of blood cancer. It acts as a potent inhibitor of BRD4, a member of the BET protein family, which is involved in the regulation of gene expression. By suppressing c-Myc expression, BI 2536 can potentially halt the progression of multiple myeloma and improve patient outcomes.

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 
• 755039-55-5 (R)-2-chloro-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one 
• 876126-60-2 4-amino-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide 
• 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 
• 755039-52-2 (R)-methyl 2-(cyclopentylamino)butanoate 
• 5081-36-7 3-methoxy-4-nitrobenzoic acid 
• 876126-59-9 3-methoxy-N-(1-methylpiperidin-4-yl)-4-nitrobenzamide 

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.

BRD4 Structure-Activity Relationships of Dual PLK1 Kinase/BRD4 Bromodomain Inhibitor BI-2536

A focused library of analogues of the dual PLK1 kinase/BRD4 bromodomain inhibitor BI-2536 was prepared and then analyzed for BRD4 and PLK1 inhibitory activities. Particularly, replacement of the cyclopentyl group with a 3-bromobenzyl moiety afforded the most potent BRD4 inhibitor of the series (39j) with a Ki = 8.7 nM, which was equipotent against PLK1. The superior affinity of 39j over the parental compound to BRD4 possibly derives from improved interactions with the WPF shelf. Meanwhile, substitution of the pyrimidine NH with an oxygen atom reversed the PLK1/BRD4 selectivity to convert BI-2536 into a BRD4-selective inhibitor, likely owing to the loss of a critical hydrogen bond in PLK1. We believe further fine-tuning will furnish a BRD4 "magic bullet" or an even more potent PLK1/BRD4 dual inhibitor toward the expansion and improved efficacy of the chemotherapy arsenal.

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

SULFONYL AMIDE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH

The present invention relates to a compound of the formula I wherein R1 to R6, A, B, n and m are as defined herein. Such novel sulfonyl amide derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

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.

COMBINATIONS FOR THE TREATMENT OF DISEASES INVOLVING CELL PROLIFERATION

The present invention relates to a pharmaceutical composition for the treatment of diseases which involve cell proliferation. The invention also relates to a method for the treatment of said diseases, comprising co-administration of a compound 1 of Formula (I) wherein the groups L, R1, R2, R3, R4 and R5 have the meanings given in the claims and specification, optionally in form of its tautomers, racemates, enantiomers, diastereomers and the mixtures thereof and optionally in form of the pharmacologically acceptable acid addition salts, solvates, hydrates, polymorphs, physiologically functional derivatives or prodrugs thereof, and of an effective amount of an active compound 2 and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of a compound 1 of Formula (I) and of an effective amount of an active compound 2 and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.

DIHYDROPTERIDINONES FOR THE TREATMENT OF CANCER DISEASES

The present invention relates to the use of a compound of general Formula (1), optionally in form of its tautomers, racemates, enantiomers, diastereomers and the mixtures thereof and optionally in form of the pharmacologically acceptable acid addition salts, solvates, hydrates, polymorphs, physiologically functional derivatives or prodrugs thereof, for the preparation of a pharmaceutical composition for the treatment of diseases characterized by abnormal cell proliferation in a human or non-human mammalian body by inhibition of polo like kinases as mitotic regulators.

Hydrates and polymorphs of 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, process for their manufacture and their use as medicament

Disclosed are hydrates and polymorphs of 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, processes for preparing them and their use as pharmaceutical compositions.

Storage stable perfusion solution for dihydropteridinones

Disclosed are storage stable aqueous infusible or injectable solutions containing an active substance of general formula (I) wherein the groups L, R1, R2, R3, R4 and R5 have the meanings given in the claims and in the specification, and an amount of a physiologically acceptable acid or mixture of acids sufficient to dissolve the active substance and act as a stabiliser, optionally together with other formulating excipients suitable for parenteral administration, and a process for preparing the infusible or injectable solutions according to the invention.

New dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions

The present invention relates to new dihydropteridinones of general formula (I) wherein the groups L and R1- R5 have the meanings given in the claims and specification, the isomers thereof, processes for preparing these dihydropterid