755038-65-4 Usage
Description
Volasertib (BI 6727) is a highly potent and selective inhibitor of Polo-like kinase 1 (Plk1) with an IC50 of 0.87 nM in a cell-free assay. It demonstrates greater selectivity against Plk2 and Plk3, making it a promising candidate for targeting cancer cells. Volasertib has shown efficacy in multiple solid xenograft tumor models and in clinical studies for patients with acute myeloid leukemia. Additionally, it has been found to potently inhibit BRD4, which is involved in various cellular processes.
Uses
Used in Anticancer Applications:
Volasertib (BI 6727) is used as a targeted therapy for the treatment of various types of cancer, including solid tumors and acute myeloid leukemia. It works by inhibiting the activity of Plk1, a protein that plays a critical role in controlling multiple essential steps of mitosis. By targeting Plk1, Volasertib disrupts the cell division process, leading to the inhibition of cancer cell growth and proliferation.
Used in Drug Development:
Volasertib (BI 6727) is used as a research tool in the development of new cancer therapies. Its potent and selective inhibition of Plk1 makes it a valuable compound for studying the role of this enzyme in cancer cell division and for identifying potential synergistic effects when combined with other anticancer agents.
Used in Preclinical and Clinical Research:
Volasertib (BI 6727) is used as a test compound in preclinical and clinical studies to evaluate its safety, efficacy, and potential side effects. These studies are essential for determining the optimal dosage, administration route, and treatment duration for various types of cancer and for identifying any potential drug interactions or contraindications.
Used in Drug Combination Strategies:
Volasertib (BI 6727) is used in combination with other chemotherapeutic agents to enhance the overall efficacy of cancer treatment. By targeting multiple cellular pathways simultaneously, combination therapies can potentially overcome drug resistance and improve treatment outcomes for patients with cancer.
Used in Drug Delivery Systems:
Volasertib (BI 6727) can be incorporated into novel drug delivery systems to improve its bioavailability, delivery, and therapeutic outcomes. These systems may include organic and metallic nanoparticles, liposomes, or other advanced drug carriers designed to enhance the transport and targeting of Volasertib to cancer cells, thereby increasing its effectiveness and reducing potential side effects.
Features
A high volume of distribution, indicating good tissue penetration, and a long terminal half-life.
In vitro
Like BI2536, BI6727 is an ATP-competitive kinase inhibitor from the dihydropteridinone class of compounds. In addition to Plk1, BI6727 also potently inhibits two closely related kinases Plk2 and Plk3 with IC50 of 5 nM and 56 nM, respectively. BI6727 at concentrations up to 10 μM displays no inhibitory activity against a panel of >50 other kinases. BI6727 inhibits the proliferation of multiple cell lines derived from various cancer tissues, including HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji cells with EC50 of 23 nM, 21 nM, 11 nM, 15 nM, 32 nM, 36 nM, and 37 nM, respectively. BI6727 treatment (100 nM) in NCI-H460 cells induces an accumulation of mitotic cells with monopolar spindles and positive staining for histone H3 phosphoserine 10, confirming that cells are arrested early in the M phase, followed by induction of apoptosis. Low nanomolar concentrations of BI6727 display potent inhibitory activity against neuroblastoma (NB) tumor-initiating cells (NB TIC) with EC50 of 21 nM, whereas only micromolar concentrations of BI6727 are cytotoxic for normal pediatric neural stem cells. BI6727 induces growth arrest of Daoy and ONS-76 medulloblastoma cells similar to BI 2536.
In vivo
Administration of BI6727 significantly inhibits the growth of multiple human carcinoma xenografts including HCT116, NCI-H460, and taxane-resistant CXB1 colon carcinoma, accompanied by an increase in the mitotic index as well as an increase in apoptosis. In in vivo studies, BI6727 shows better toxicity and pharmacokinetic profile compared to BI2536.
References
1) Rudolph?et al.?(2009)?BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity; Clin. Cancer Res.?15?3094
2) Rudolph?et al.?(2015)?Efficacy and Mechanism of Action of Volasertib, a Potent and Selective Inhibitor of Polo-Like Kinases, in Preclinical Models of Acute Myeloid Leukemia; J. Pharmacol. Exp. Ther.?352?579
3) Ciceri?et al.?(2014)?Dual kinase-bromodomain inhibitors for rationally designed polypharmacology; Nat. Chem. Biol.?10?305
Check Digit Verification of cas no
The CAS Registry Mumber 755038-65-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,5,5,0,3 and 8 respectively; the second part has 2 digits, 6 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 755038-65:
(8*7)+(7*5)+(6*5)+(5*0)+(4*3)+(3*8)+(2*6)+(1*5)=174
174 % 10 = 4
So 755038-65-4 is a valid CAS Registry Number.
755038-65-4Relevant articles and documents
Process for manufacturing dihydropteridinones and intermediates thereof
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, (2013/03/26)
The present invention relates to an improved process for manufacturing dihydropteridinones of general formula (12) as well as intermediates thereof, wherein the groups R1, R2, R3, R4, and R5 have the
CRYSTALLINE FORM OF A DIHYDROPTERIDIONE DERIVATIVE
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Page/Page column 22, (2009/04/25)
The present invention relates to a crystalline form a dihydropteridione derivative, namely a crystalline form of the free base N- [trans-4- [4- (cyclopropylmethyl) - 1-piperazinyl] cyclohexyl] -4- [[(7R) -7-ethyl-5, 6. 7, 8 - tetrahydro - 5 -methyl - 8 -
TRIHYDROCHLORIDE FORMS OF A DIHYDROPTERIDINONE DERIVATIVE AND PROCESSES FOR PREPARATION
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Page/Page column 14-15, (2008/06/13)
The present invention relates to a specific salt of a dihydropteridione derivative, namely the trihydrochloride salt of the compound N-[trans-4-[4-(cyclopropylmethyl)-1- piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl
