Aurora kinase a inhibitor alisertib. Medical search. Frequent questions

Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. (aacrjournals.org)
The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells. (stembook.org)

Alisertib (MLN8237) is an orally available selective aurora A kinase inhibitor developed by Takeda. (wikipedia.org)
Furthermore, combinations of YK-4-279 with vincristine, paclitaxel or the Aurora kinase A inhibitor MLN8237/Alisertib show strong synergy, particularly at low doses. (researcher-app.com)

Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. (unitn.it)
Studies of alisertib in combination with other anticancer drugs in these tumor types are warranted. (aacrjournals.org)
Aurora kinase A is required for proper mitotic spindle formation and progression through mitosis, and its overexpression in various tumor types is associated with poor prognosis. (aacrjournals.org)
Alisertib exhibited a manageable safety profile with similar adverse events across all five tumor types, including neutropenia, fatigue, alopecia, anemia, and diarrhea. (aacrjournals.org)
Vraag: Herstelt behandeling met alisertib de gevoeligheid voor fulvestrant en verbetert het de tumor objectieve response rates (ORR's) in vergelijking met alisertib monotherapie bij patiënten met hormoonresistente gemetastaseerde borstkanker? (kanker-actueel.nl)
Question Does treatment with alisertib restore fulvestrant sensitivity and improve tumor objective response rates (ORRs) compared with alisertib monotherapy in patients with endocrine-resistant metastatic breast cancer? (kanker-actueel.nl)
Replimune Group, Inc. a clinical stage biotechnology company pioneering the development of a novel portfolio of tumor-directed oncolytic immunotherapies, and Incyte a global biopharmaceutical company, today announced a clinical trial collaboration and supply agreement to study RP1, Replimune's lead product candidate, in combination with INCB99280, Incyte's small molecule oral PD-L1 inhibitor. (biotechnology.report)
Puma Biotechnology, Inc. a biopharmaceutical company, announced an agreement with Takeda to license the worldwide research and development and commercial rights to alisertib, a selective, small-molecule, orally administered inhibitor of aurora kinase A. Alisertib is an adenosine triphosphate-competitive and reversible inhibitor of aurora kinase A and results in disruption of mitosis leading to apoptosis of rapidly proliferating tumor cells that are dependent on aurora kinase A. Alisertib h. (biotechnology.report)
In fact, a critical advantage in treat Inhibitors,Modulators,Libraries ing tumors with nanoparticulate systems comes from the unique patho physiological characteristics of solid tu mors extensive angiogenesis and hence hypervasculari zation, coupled with poor lymphatic drainage, which allow a facilitate extravasation into the tumor Inhibitors,Modulators,Libraries and EPR effect of colloidal systems. (chk1inhibitor.com)
14 18 19 Inhibition of PI3K/Akt/mTOR pathway can be reversed using specific inhibitors of the pathway and decrease tumor metastasis. (highwire.org)
We studied 5 consecutive cases of GCT involving the distal radius operated by en-bloc resection of tumor followed by reconstruction with ipsilateral non-vascularized fibular graft with a minimum 1 year follow-up. (jbstjournal.com)
Chiauranib (CS2164) is an orally active multi-target inhibitor against tumor angiogenesis. (medchemexpress.com)
Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION. (lookformedical.com)
The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.com)

Alisertib induces cell cycle arrest and autophagy and suppresses epithelial-to-mesenchymal transition involving PI3K/Akt/mTOR and sirtuin 1-mediated signaling pathways in human pancreatic cancer cells. (stembook.org)

ALS also exhibited various regulatory effects on the PI3K/Akt and mitogen-activated protein kinase (MAPK) pathways, the two dominant RAS signaling pathways, and induced apoptosis and autophagy in a RAS allele-specific manner. (bvsalud.org)
Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. (oaepublish.com)

Preclinical studies have shown that alisertib, an oral, selective inhibitor of Aurora kinase A, results in mitotic defects and induces cell death, and preliminary antitumor activity has been observed in phase I clinical trials of both hematologic and solid tumors. (aacrjournals.org)

The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells. (stembook.org)
It will also include compounds known to be active on Aurora kinases, e.g. barasertib, alisertib, danusertib [7-8]. (edu.pl)
Danusertib is a pyrrolo-pyrazole and aurora kinase inhibitor with IC 50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively. (medchemexpress.com)

Exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. (unitn.it)
The safety and activity of alisertib was evaluated in patients with relapsed or refractory solid tumors. (aacrjournals.org)
Melichar and colleagues report the results of a phase II study evaluating the safety and activity of alisertib in patients with one of five predefined types of advanced refractory or relapsed solid tumors characterized by high Aurora kinase A expression. (aacrjournals.org)
Although additional work is needed to understand the differential activity of alisertib among solid tumors and to identify predictive markers of response, these findings demonstrate the antitumor activity of this inhibitor in patients with advanced breast cancer and SCLC and support future clinical trials of alisertib in combination with other therapeutic agents. (aacrjournals.org)

Alisertib (MLN 8237) is an orally active and selective Aurora A kinase inhibitor ( IC 50 =1.2 nM), which binds to Aurora A kinase resulting in mitotic spindle abnormalities, mitotic accumulation. (medchemexpress.com)
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)

For example, alteronol (protein kinase B (PKB, also known as Akt)/the mechanistic target of rapamycin (mTOR) inhibitor) induces autophagy in melanoma cancer cells and inhibits their metastasis and migration via inhibition of EMT. (highwire.org)
7 8 Alisertib (inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR) induces autophagy and inhibits metastasis in ovarian cancers cells via inhibition of EMT. (highwire.org)
A test kit to evaluate the inhibition of Aurora A kinase (CycLex Aurora Family Kinase Assay / Inhibitor Screening Kit) will be performed. (edu.pl)
We hypothesized that co-expression of Myc and Bcl2 is functionally equivalent to translocation evident in DHL targetable by inhibition of Aurora in the actual existence of MTAs (e.g. (immune-source.com)

We see that there is CDK and there is synergistic activity for CDK, PI3K, and then ER, and so we're trying to see if for patients with PIK3C mutations could there be a strategy for combining the triplet, maybe with an AKT inhibitor. (onclive.com)

HDAC inhibitors are a class of anticancer agents. (cancer-research-network.com)
Novel therapeutic options that have been evaluated include histone deacetylase (HDAC) inhibitors (HDACi), pralatrexate, and monoclonal antibodies [ 6 ]. (biomedcentral.com)
HDAC inhibitors increase the acetylation of lysine residues on histone proteins, thereby changing the gene expression pattern for important genes involved in cell cycle, maturation, and cell death. (aml-hub.com)

Here we show that YK-4-279 suppressed growth and triggered apoptosis in nine neuroblastoma cell lines, while BRD32048, another ETV1 inhibitor, was ineffective. (researcher-app.com)
Alisertib (MLN 8237) induces apoptosis and autophagy through targeting the AKT / mTOR / AMPK /p38 pathway in leukemic cells. (medchemexpress.com)

Applying "drug target constellation" (DTECT) mapping, we further show that protein levels of TTF1 and cMYC predict response to targeted therapies including aurora kinase, Bcl2, and HSP90 inhibitors. (oncotarget.com)
Although Aurora A kinase is a known protein and numerous experiments have been carried out on it for years, so far no combination of numerical and experimental methods has been used in the study of its inhibitors. (edu.pl)
Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.com)
An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
100 x 10(3)/mu l) were investigated for the presence of H. pylori infection and its eradication GW-572016 Protein Tyrosine Kinase inhibitor by H pylori stool antigen (HpSA) enzyme immunoassay method (EIA). (alk-inhibitors.com)

PF-03814735 is a potent, orally available, ATP-competitive and reversible aurora A and aurora B inhibitor with IC 50 s of 0.8 and 0.5 nM, respectively. (medchemexpress.com)
CCT 137690 is a potent and orally available aurora kinase inhibitor with IC 50 s of 15, 25, and 19 nM for aurora A, B and C, respectively. (medchemexpress.com)

Importance Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. (kanker-actueel.nl)
Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. (kanker-actueel.nl)
Aurora A kinase (AURKA) is crucial in oncogenesis, because its overexpression or amplification may incline the development of various types of cancer, including MM. Therefore, inhibitors of AURKA are innovative and promising targets. (hacettepe.edu.tr)
In the present study, based on virtual drug screening of more than 48,000 natural compounds, the antibiotic deschloro-chlorotricin (DCCT) has been identified to bind to AURKA with even higher binding affinity (free bindung energy: -12.25 kcal/mol) than the known AURKA inhibitor, alisertib (free binding energy: -11.25 kcal/mol). (hacettepe.edu.tr)
Thus, DCCT may be a promising lead structure for further derivatization and the development of specific AURKA inhibitors in MM therapy. (hacettepe.edu.tr)

There are various approaches we're trying to take in clinic to address this post-CDK4/6 inhibitor progression. (onclive.com)
Aurora kinases control multiple events during cell cycle progression and are essential for mitotic and meiotic bipolar spindle assembly and function. (cancer-research-network.com)

Barasertib-HQPA (AZD2811) is a highly selective Aurora B inhibitor with an IC 50 of 0.37 nM in a cell-free assay. (medchemexpress.com)

Aurora kinases belong to serine/threonine kinases. (cancer-research-network.com)
Aurora A kinase is one of the serine-threonine kinases that control mitotic and meiosis processes in cells. (edu.pl)
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)

240)] (14) for correlative concept of Aurora A, Aurora B, MYC and BCL2 with respect to every single (Table 1) exhibited that Aurora A and B manifestation is very related in both DLBCL and MCL. (immune-source.com)
BCL2 concept moderately but tremendously related with Aurora A and B in DLBCL although not in MCL. (immune-source.com)

Capsaicin as a compound with a potential to inhibit Aurora A kinase was selected because capsaicin supplementation had previously been shown to abolish resistance to cisplatin treatment induced by overexpression of Aurora A kinase [4]. (edu.pl)
In human, aurora-A has focused a lot of attention, since its overexpression has been found to be correlated with the grade of various solid tumours. (lookformedical.com)
Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
However, overexpression of aurora-A in particular cell lines such as NIH3T3 is sufficient to induce growth on soft agar. (lookformedical.com)

Remedy with alisertib up-controlled outrageous style p53 in Granta-519 MCL cells specifying G0/G1 arrest consequent to G2/M checkpoint activation. (immune-source.com)

JNJ-7706621 is a potent aurora kinase inhibitor, and also inhibits CDK1 and CDK2 , with IC 50 s of 9 nM, 3 nM, 11 nM, and 15 nM for CDK1 , CDK2 , aurora-A and aurora-B , respectively. (medchemexpress.com)
Hesperadin is an ATP competitive indolinone inhibitor of Aurora A and B . Hesperadin inhibits Aurora B with an IC 50 of 250 nM. (medchemexpress.com)

The Aurora kinase A inhibitor alisertib shows activity in breast cancer and small cell lung cancer. (aacrjournals.org)
Treatment with alisertib resulted in objective partial responses in nine (18%) of 49 patients with breast cancer, in particular those with hormone receptor-positive or HER2-positive disease, and ten (21%) of 48 patients with SCLC. (aacrjournals.org)
Findings In this phase 2 randomized clinical trial of 91 patients with endocrine-resistant, metastatic breast cancer who were previously treated with a cyclin-dependent kinase 4/6 inhibitor, participants were randomized to receive treatment with alisertib alone or combined with fulvestrant. (kanker-actueel.nl)
Meaning The trial results found that while alisertib did not restore fulvestrant sensitivity and increase ORRs, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and cyclin-dependent kinase 4/6 inhibitor-resistant metastatic breast cancer. (kanker-actueel.nl)
In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. (pumabiotechnology.com)

AT9283 is a multi-targeted kinase inhibitor with potent activity against Aurora A/B , JAK2 /3 , Abl (T315I) and Flt3 ( IC 50 s ranging from 1 to 30 nM). (medchemexpress.com)
Within this analysis, we reveal the efficiency and tolerability from the pan HDACi pracinostat in different in vitro and also in vivo types of AML, and display synergistic benefits at a number of concentrations in conjunction with the JAK2/FLT-3 inhibitor pacritinib in both the in vitro and also in vivo placing. (immune-source.com)

Absolutely, I'll add to the list of CDK4/6 inhibitor resistance alterations that we're thinking about. (onclive.com)

Enhancing the Inhibitors,Modulators,Libraries production of flavonoids in crop plants Inhibitors,Modulators,Libraries can there fore give an important boost to their Inhibitors,Modulators,Libraries nutritional value, which makes knowledge of expression and regulation of the flavonoid pathway important. (chk1inhibitor.com)
As both ALK and RAS signal through the MEK/ERK pathway, we sought to evaluate two previously reported inhibitors of ETS-related transcription factors, which are transcriptional mediators of the Ras-MEK/ERK pathway in other cancers. (researcher-app.com)

This influence had not been noticed in U-2932 DLBCL cells exactly where p53 is mutated (Number 1) implicating a differential reaction to alisertib. (immune-source.com)

Conclusions: Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib. (unitn.it)

The aim of the present study was to examine the effects of alisertib (ALS) on RAS signaling pathways against a panel of colorectal cancer (CRC) cell lines and engineered Flp-In stable cell lines expressing different Kirsten rat sarcoma virus (KRAS) mutants. (bvsalud.org)

Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora-N-myc complex disruption. (unitn.it)

The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)

In the first stage of the project, using molecular docking to find potential Aurora A kinase inhibitors, a group of compounds (mainly of natural origin), showing structural similarities with capsaicin, will be tested. (edu.pl)

Purpose: Aurora kinases are overexpressed or amplified in numerous malignancies. (operatiebrp.nl)

The arrangement and the interaction network formed by the inhibitor molecule bound by Aurora A kinase will serve as a benchmark for the results obtained with the test compounds. (edu.pl)

AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor with IC 50 of 5 nM, 4 nM and 1 nM for Aurora A , B and C , respectively. (medchemexpress.com)
GSK-1070916 is a potent and selective ATP-competitive inhibitor of aurora B and aurora C with K i s of 0.38 and 1.5 nM, respectively, and is >250- fold selective over Aurora A. (medchemexpress.com)
CYC-116 is a potent aurora A and aurora B inhibitor with K i s of 8 and 9 nM, respectively. (medchemexpress.com)
TCS7010 is a potent and highly selective Aurora A inhibitor with with an IC 50 of 3.4 nM. (medchemexpress.com)
SNS-314 mesylate is a potent and selective aurora kinase inhibitor with IC 50 s of 9, 31, and 6 nM for aurora A, B and C, respectively. (medchemexpress.com)

Such tests are commonly used in the evaluation of Aurora A inhibitors [9]. (edu.pl)

Patients and Methods: Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. (unitn.it)
Work done from the Boston group had talked about the aurora kinase amplifications, and we've seen aurora kinase inhibitors such as alisertib that were studied in patients who progressed on CDK4/6 inhibitors. (onclive.com)

With alisertib, we did see an overall response rate of 20%, which was rather respectful. (onclive.com)

MYC expression exhibited a strong link with Aurora A and B in MCL but relatively linked with Aurora A and B in DLBCL. (immune-source.com)

Anatomy12

Organisms4

Diseases5

Chemicals and Drugs74

Analytical, Diagnostic and Therapeutic Techniques and Equipment6

Phenomena and Processes39

Information Science2

Investigational aurora kinase A in2

MLN82372

Tumor14

Induces cell cycle1

Mitogen-activa2

Selective inhibitor1

Danusertib3

Tumors4

Mitotic spindle2

Inhibition4

PI3K1

HDAC3

Apoptosis2

Protein7

Orally available2

AURKA5

Progression2

Assay1

Serine4

Bcl22

Overexpression4

Arrest1

Inhibits2

Breast cancer5

JAK22

Resistance1

Pathway2

Differential1

Clinical1

Pathways1

Disruption1

Gene1

Molecular1

Malignancies1

Interaction1

Potent5

Evaluation1

Patients2

Response1

Expression1