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DRUG:

alisertib (MLN8237)

i
Other names: MLN8237, MLN 8237, MLN-8237
Company:
Puma, Takeda
Drug class:
Aurora kinase A inhibitor
5d
Only Infant MLL-Rearranged Leukemia Is Susceptible to an Inhibition of Polo-like Kinase 1 (PLK-1) by Volasertib. (PubMed, Int J Mol Sci)
Importantly, the poor response could be overcome by a combinatorial strategy with alisertib, an Aurora kinase A inhibitor. Our study emphasizes the importance of considering the cell of origin in therapeutic decision-making and provides the rationale for evaluating volasertib and alisertib in MLLr leukemia.
Journal
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CD34 (CD34 molecule) • AURKA (Aurora kinase A) • PLK1 (Polo Like Kinase 1)
|
MLL rearrangement
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volasertib (NBL-001) • alisertib (MLN8237)
6d
Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer (clinicaltrials.gov)
P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Sep 2023 --> May 2025
Trial primary completion date
|
PD-L1 expression
|
Keytruda (pembrolizumab) • alisertib (MLN8237)
16d
Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence. (PubMed, iScience)
Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. Targeting STAT3 restores sensitivity to each of these drugs by depleting the senescent subpopulation and inducing quiescent cells to enter the mitotic cycle. These results support a therapeutic strategy of targeting STAT3-dependent therapy-induced senescence to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma.
Journal
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STAT3 (Signal Transducer And Activator Of Transcription 3) • TGFB1 (Transforming Growth Factor Beta 1)
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volasertib (NBL-001) • alisertib (MLN8237) • ispinesib (SB-715992)
26d
Phase 1/2 Study of the Aurora Kinase A Inhibitor Alisertib and Pembrolizumab in Refractory, Rb-Deficient Head and Neck Squamous Cell Carcinomas. (PubMed, Clin Cancer Res)
The combination of alisertib and pembrolizumab was well tolerated and led to prolonged SD in some immunotherapy-resistant patients, supporting our hypothesis that Aurora kinase A inhibition can reverse immunotherapy resistance of retinoblastoma protein-deficient HNSCC.
P1/2 data • Journal
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AURKA (Aurora kinase A)
|
Keytruda (pembrolizumab) • alisertib (MLN8237)
2ms
Low-level Aurora kinase A (AURKA) amplification as a novel personalized biomarker of CDK4/6 inhibitor (CDK4/6i) resistance in patients with hormone-receptor positive (HR+) metastatic breast cancer (SABCS 2024)
In this large, real-world translational research cohort of pts with HR+ MBC, low-level AURKA copy number gain was common. These data report the first evidence suggesting that low-level amplifications in AURKA, which conventional sequencing platforms miss, can provoke meaningful changes in gene expression as assessed via RNA transcriptome analysis. Further, low-level AURKA amplifications predict inferior outcomes on CDK4/6i for pts with HR+ MBC.
Clinical • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • AURKA (Aurora kinase A)
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HR positive • HER-2 negative • RB1 mutation
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Tempus xT Assay • Tempus xR
|
alisertib (MLN8237)
2ms
Enrollment change • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 amplification • HER-2 negative • HER-2 expression • ER negative • HER-2 negative + ER positive
|
fulvestrant • alisertib (MLN8237)
2ms
Enrollment open • Combination therapy • Metastases
|
tamoxifen • fulvestrant • alisertib (MLN8237)
2ms
Differential regulation of expression of the protein kinases DYRK1A and DYRK1B in cancer cells. (PubMed, Sci Rep)
Consistently, AURK inhibitors VX-680 (tozasertib), MLN8237 (alisertib), AZD1152-HQPA (barasertib) resulted in the upregulation of DYRK1B expression in A549 cells. In summary, our findings indicate that the expression of DYRK1A and DYRK1B is differentially regulated in cancer cells and reveal that the kinase inhibitor XMU-MP-1 increases DYRK1B expression likely through off target inhibition of Aurora kinases.
Journal
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AURKA (Aurora kinase A) • AURKB (Aurora Kinase B) • DYRK1A (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A) • DYRK1B (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B)
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alisertib (MLN8237) • barasertib-HQPA (AZD2811) • tozasertib (MK-0457)
2ms
Study to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast Cancer (clinicaltrials.gov)
P2, N=169, Completed, US Oncology Research | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Aug 2024 | Trial primary completion date: Dec 2023 --> Apr 2024
Trial completion • Trial completion date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 negative • ER negative • PGR negative
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albumin-bound paclitaxel • alisertib (MLN8237)
4ms
Aurora Kinase A Inhibition Potentiates Platinum and Radiation Cytotoxicity in Non-Small-Cell Lung Cancer Cells and Induces Expression of Alternative Immune Checkpoints. (PubMed, Cancers (Basel))
Both AURKA inhibition by alisertib and inducible AURKA knockdown potentiated the cytotoxic effects of cisplatin and radiation, leading to tumor regression in doxycycline-inducible xenograft mice. In conclusion, our study demonstrates that AURKA inhibition enhances the efficacy of platinum-based chemotherapy in NSCLC cells and modulates the expression of multiple immune checkpoints. Therefore, combinatory regimens with AURKA inhibitors should be strategically designed and further studied within the evolving landscape of chemo-immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD276 (CD276 Molecule) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1) • AURKA (Aurora kinase A) • HHLA2 (HERV-H LTR-Associating 2)
|
cisplatin • alisertib (MLN8237)
4ms
High Mobility Group AT-hook 2: A Biomarker Associated with Resistance to Enzalutamide in Prostate Cancer Cells. (PubMed, Cancers (Basel))
The HMGA2 changes were linked to treatments like enzalutamide, abiraterone, or alisertib, with amplifications more prevalent in bone, lymph node, and liver metastases. Conclusively, HMGA2 is a potential biomarker for enzalutamide resistance in mPCa, independent of Snail and AR signaling, and alisertib may be an effective treatment for mPCa that expresses HMGA2.
Journal
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HMGA2 (High mobility group AT-hook 2)
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Xtandi (enzalutamide) • abiraterone acetate • alisertib (MLN8237)
5ms
BRCA1 orchestrates the response to BI-2536 and its combination with alisertib in MYC-driven small cell lung cancer. (PubMed, Cell Death Dis)
Our findings indicate that the BRCA1 and MYC/MYCN-RAD51 axes govern the response of small cell lung cancer to BI-2536 and its combination with alisertib. This study propose the combined use of BI-2536 and alisertib as a novel therapeutic strategy for the treatment of SCLC patients with MYC/MYCN activation.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • RAD51 (RAD51 Homolog A) • AURKA (Aurora kinase A)
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alisertib (MLN8237) • BI2536
5ms
AURKA activates FOXO3a to form a positive feedback loop in the proliferation and migration of keloid fibroblasts. (PubMed, Adv Wound Care (New Rochelle))
AURKA/FOXO3a loop promotes the proliferation and migration of keloid fibroblasts via AKT signaling. Despite the anti-keloid effects of AKIs, AURKA acts as a transcription factor independently of kinase activity, deepening our understanding on AKI insensitivity.
Journal
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AURKA (Aurora kinase A)
|
alisertib (MLN8237)
5ms
Suppressing PD-L1 Expression via AURKA Kinase Inhibition Enhances Natural Killer Cell-Mediated Cytotoxicity against Glioblastoma. (PubMed, Cells)
Combination therapy involving anti-PD-1 treatment and Alisertib significantly prolonged overall survival compared to vehicle treatment. These findings suggest that targeting AURKA could have therapeutic implications for modulating the immune environment within GBM cells.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
|
alisertib (MLN8237)
6ms
Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer (clinicaltrials.gov)
P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: May 2025 --> Sep 2023
Trial primary completion date
|
Keytruda (pembrolizumab) • alisertib (MLN8237)
6ms
Resistance to Spindle Inhibitors in Glioblastoma Depends on STAT3 and Therapy Induced Senescence. (PubMed, bioRxiv)
Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. These results support a therapeutic strategy of targeting STAT3-dependent therapy-induced senescence to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma. • Resistance to non-microtubule spindle inhibitors limits their efficacy in glioblastoma and depends on STAT3.• Resistance goes hand in hand with development of therapy induced senescence (TIS).• Spindle inhibitor resistant glioblastomas consist of three cell subpopulations-proliferative, quiescent, and TIS-with proliferative cells sensitive and quiescent and TIS cells resistant.• TIS cells secrete TGFβ, which induces proliferative cells to become quiescent, thereby expanding the population of resistant cells in a spindle inhibitor resistant glioblastoma• Treatment with a STAT3 inhibitor kills TIS cells and restores sensitivity to spindle inhibitors.
Journal
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STAT3 (Signal Transducer And Activator Of Transcription 3) • TGFB1 (Transforming Growth Factor Beta 1)
|
volasertib (NBL-001) • alisertib (MLN8237) • ispinesib (SB-715992)
6ms
Aurkin-A, a TPX2-aurora a small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma. (PubMed, Neoplasia)
In a VAL mouse xenograft model, we show polyploidy generation in alisertib treated mice versus vehicle control or Aurkin A. Aurkin A plus alisertib significantly reduced polyploidy to vehicle control levels. Our in vitro and in vivo studies show that Aurkin A synergizes with alisertib and significantly decreases the alisertib dose needed to disrupt polyploidy while increasing apoptosis in DLBCL cells.
Journal
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AURKA (Aurora kinase A) • GMNN (Geminin DNA replication inhibitor) • CDT1 (Chromatin Licensing And DNA Replication Factor 1)
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alisertib (MLN8237)
6ms
Aurora Kinase A inhibition enhances DNA damage and tumor cell death with 131I-MIBG therapy in high-risk neuroblastoma. (PubMed, EJNMMI Res)
The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.
Journal • Tumor cell
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AURKA (Aurora kinase A)
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alisertib (MLN8237) • Azedra (iobenguane I 131)
7ms
NCI-2019-05913: Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer (clinicaltrials.gov)
P1, N=38, Recruiting, Collin Blakely | Active, not recruiting --> Recruiting | N=22 --> 38 | Trial completion date: May 2025 --> Dec 2026 | Trial primary completion date: May 2025 --> Dec 2026
Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • alisertib (MLN8237)
7ms
Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
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Tagrisso (osimertinib) • sapanisertib (CB-228) • alisertib (MLN8237)
7ms
Development and therapeutic evaluation of 5D3(CC-MLN8237)3.2 antibody-theranostic conjugates for PSMA-positive prostate cancer therapy. (PubMed, Front Pharmacol)
The novel ATC successfully controlled the growth of PSMA (+) tumors in preclinical settings with minimal systemic toxicities. The therapeutic efficacy and favorable safety profile of novel 5D3(CC-MLN8237)3.2 ATC demonstrates their potential use as a theranostic against aggressive PC.
Journal
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AURKA (Aurora kinase A)
|
FOLH1 positive
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alisertib (MLN8237)
8ms
A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors. (PubMed, Cancers (Basel))
Dual targeting of Aurora A kinase and mTOR resulted in marginal clinical benefit in a population of patients with refractory solid tumors, including pancreatic adenocarcinoma, though individual patients experienced significant response to therapy. Correlatives indicate apoptotic response and tumor immune cell infiltrate may affect clinical outcomes.
P1 data • Journal • Metastases
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ER (Estrogen receptor) • AURKA (Aurora kinase A)
|
ER positive
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sapanisertib (CB-228) • alisertib (MLN8237)
8ms
Aurora kinase A inhibition plus Tumor Treating Fields suppress glioma cell proliferation in a cilium-independent manner. (PubMed, Transl Oncol)
Thus, Alisertib-mediated effects on glioma cilia may be a useful biomarker of drug efficacy within tumor tissue. Considering Alisertib can cross the blood brain barrier and inhibit intracranial growth, our data warrant future studies to explore whether concomitant Alisertib and TTFields exposure prolongs survival of brain tumor-bearing animals in vivo.
Journal
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AURKA (Aurora kinase A) • AURKB (Aurora Kinase B)
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alisertib (MLN8237)
8ms
Synergy of EGFR and AURKA inhibitors in KRAS-mutated non-small cell lung cancers. (PubMed, Cancer Res Commun)
Analysis of signaling pathways demonstrated that the combination of erlotinib and alisertib was more effective than single agent treatments at reducing activity of EGFR and pathway effectors following either brief or extended administration of the drugs. In sum, this study indicates value of inhibiting EGFR in KRASmut NSCLC, and suggests the specific value of dual inhibition of AURKA and EGFR in these tumors.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • EGFR mutation • AURKA expression • KRAS expression
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erlotinib • alisertib (MLN8237)
8ms
New P2 trial • Combination therapy • Metastases
|
tamoxifen • fulvestrant • alisertib (MLN8237)
9ms
Discovery of a long half-life AURKA inhibitor to treat MYC-amplified solid tumors as a monotherapy and in combination with everolimus. (PubMed, Mol Cancer Ther)
Aurora kinase inhibitors such as alisertib can destabilize MYC-family oncoproteins and have demonstrated compelling anti-tumor efficacy. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC- driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC- and/or N-MYC.
Journal • Combination therapy
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYC amplification • MYC overexpression • MYC expression
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everolimus • alisertib (MLN8237)
9ms
The Current Therapeutic Landscape for Metastatic Prostate Cancer. (PubMed, Pharmaceuticals (Basel))
Among these, the trials administering drugs Alisertib or Cabozantinib, which target AURKA or receptor tyrosine kinases, respectively, appear to have promising results...Consequently, the landscape of successful treatment regimens for NEPC is extremely limited. These trial results and the literature on the topic emphasize the need for new preventative measures, diagnostics, disease specific biomarkers, and a thorough clinical understanding of NEPC.
Review • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
|
PD-1 (Programmed cell death 1) • CD276 (CD276 Molecule) • DLL3 (Delta Like Canonical Notch Ligand 3) • AURKA (Aurora kinase A)
|
Cabometyx (cabozantinib tablet) • alisertib (MLN8237)
9ms
AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine synthesis. (PubMed, Cell Death Dis)
Through CRISPR metabolic screens, we identified that KEAP1-knockdown cells showed the highest sensitivity to the AURKA inhibitor MLN8237...Our study unveils the pivotal role of AURKA in amino acid metabolism and identifies a specific metabolic indication for AURKA inhibitors. These findings also provide a novel clinical therapeutic target for KEAP1-mutant/deficient NSCLC, which is characterized by resistance to radiotherapy, chemotherapy, and targeted therapy.
Journal
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KEAP1 (Kelch Like ECH Associated Protein 1) • AURKA (Aurora kinase A) • ASNS (Asparagine synthetase) • ATF4 (Activating Transcription Factor 4)
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KEAP1 mutation
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alisertib (MLN8237)
9ms
Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells. (PubMed, Br J Cancer)
AURKA inhibition holds promise as a therapeutic approach to overcome cetuximab resistance in RAS/RAF wild-type colorectal cancer, offering a potential means to counter the development of cancer stem cell phenotypes associated with cetuximab resistance.
Journal • Cancer stem
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YAP1 (Yes associated protein 1)
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RAS wild-type
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Erbitux (cetuximab) • alisertib (MLN8237)
10ms
eEF1A2 promotes PTEN-GSK3β-SCF complex-dependent degradation of Aurora kinase A and is inactivated in breast cancer. (PubMed, Sci Signal)
Reactivating this pathway using fimepinostat, which relieves inhibitory signaling directed at PTEN and increases FBXW7 expression, combined with inhibiting Aurora-A with alisertib, suppressed breast cancer cell proliferation in culture and tumor growth in vivo. The findings demonstrate a therapeutically exploitable, tumor-suppressive role for eEF1A2 in breast cancer.
Journal
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PTEN (Phosphatase and tensin homolog) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • AURKA (Aurora kinase A) • CUL1 (Cullin 1) • EEF1A1 (Eukaryotic Translation Elongation Factor 1 Alpha 1) • GSK3B (Glycogen Synthase Kinase 3 Beta) • METTL3 (Methyltransferase Like 3)
|
alisertib (MLN8237) • fimepinostat (CUDC-907)
10ms
Trial completion date • Combination therapy
|
CD4 (CD4 Molecule)
|
Rituxan (rituximab) • bortezomib • alisertib (MLN8237) • Mabtas (rituximab biosimilar)
10ms
Male meiotic spindle poles are stabilized by TACC3 and cKAP5/chTOG differently from female meiotic or somatic mitotic spindles in mice. (PubMed, Sci Rep)
MLN 8237 Aurora-A kinase inhibitor removes TACC3, not cKAP5/chTOG, disrupting spindle organization, chromosome alignment, and impacting spindle pole γ-tubulin intensity...Cold microtubule disassembly and rescue experiments in the presence of 1,6-hexanediol reinforce the concept that spermatocyte TACC3 spindle pole presence is not required for spindle pole microtubule assembly. Collectively, meiotic spermatocytes without a LISD localize TACC3 and cKAP5/chTOG exclusively at spindle poles to support meiotic spindle pole stabilization during male meiosis, different from either female meiosis or mitosis.
Preclinical • Journal
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TACC3 (Transforming acidic coiled-coil containing protein 3) • AURKA (Aurora kinase A) • CETN2 (Centrin 2)
|
alisertib (MLN8237)
10ms
Inhibition of Aurora kinase induces endogenous retroelements to induce a type I/III interferon response via RIG-I. (PubMed, Cancer Res Commun)
The anti-tumor effect of alisertib in mice was accompanied by an induction of IFN expression in HCT116 or CT26 tumors. CT26 tumor growth inhibition by alisertib was absent in NOD/SCID mice vs. WT mice, and tumors from WT mice with alisertib treatment showed increased in CD8+ T cell infiltration, suggesting that anti-tumor efficacy of AURKi depends, at least in part, on an intact immune response.
Journal
|
CD8 (cluster of differentiation 8) • IFI27 (Interferon Alpha Inducible Protein 27)
|
IFNA1 expression
|
alisertib (MLN8237)
11ms
Trial completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 amplification • HER-2 negative • HER-2 expression • ER negative
|
fulvestrant • alisertib (MLN8237)
12ms
Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer (clinicaltrials.gov)
P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025
Trial completion date • Trial primary completion date
|
PD-L1 expression
|
Keytruda (pembrolizumab) • alisertib (MLN8237)
1year
A Study of Alisertib in Patients With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov)
P2, N=60, Recruiting, Puma Biotechnology, Inc. | Not yet recruiting --> Recruiting
Enrollment open
|
alisertib (MLN8237)
1year
Nanogel enhances the efficacy of MLN8237 in treating hepatocellular carcinoma. (PubMed, J Biomater Appl)
Moreover, the MLN8237-loaded nanogel has a stronger ability to inhibit HCC cell proliferation, block cell cycle, promote apoptosis and inhibit tumor growth than free MLN8237 by suppressing aurora-A and AKT phosphorylation. In short, nanogel can enhance the efficacy of MLN8237.
Journal
|
AURKA (Aurora kinase A)
|
alisertib (MLN8237)
1year
Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation. (PubMed, Biomed Environ Sci)
Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA)...MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction. Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.
Journal
|
AURKA (Aurora kinase A)
|
alisertib (MLN8237)
1year
Increasing DAXX as a Novel Approach to Inhibit Breast Cancer Stem Cells and Estrogen Receptor-positive Tumor Recurrence (SABCS 2023)
Background: Resistance to endocrine therapy (ET; tamoxifen, aromatase inhibitors, AI, or fulvestrant) in ER+ breast cancer (BC) could be due to survival of breast cancer stem cells (BCSCs)...We discovered a novel and potent anti-BCSC gene, Death Associated Protein 6 (DAXX) through a pre-surgical biomarker window study combining ET plus a Notch inhibitor [MK-0752, a g-secretase inhibitor (GSI)]...ER+ cells were treated with kinase inhibitors for AURKA (alisertib), AURKB (barasertib), CK1 (CK-IN-1), or CK2 (CX-4945) and DAXX protein was detected by western blotting... ET decreased DAXX protein levels in ER+ PDX and human tumors. Downregulation of the DAXX protein by ET was through activation of AURKB and hyper-phosphorylation of DAXX which resulted in protein degradation and enhanced survival of BCSCs. Therefore, Inhibition of AURKB using barasertib partially restored DAXX expression, inhibited BCSCs, and delayed tumor recurrence.
Cancer stem
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ER (Estrogen receptor) • AURKA (Aurora kinase A) • NOTCH4 (Notch 4) • AURKB (Aurora Kinase B) • DAXX (Death-domain associated protein)
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ER positive
|
tamoxifen • fulvestrant • alisertib (MLN8237) • barasertib (AZD1152) • silmitasertib (CX-4945) • MK-0752
1year
A novel class of pyrazole analogues as aurora kinase A inhibitor: design, synthesis, and anticancer evaluation. (PubMed, Bioorg Chem)
Compounds5hand5eexhibited greater cytotoxicity in the series against MCF-7 and MDA-MB-231, with GI values of 0.12 µM and 0.63 µM, respectively, as compared to Imatinib (GI values of 16.08 µM and 10.36 µM)...Furthermore, compounds 5h and 5e inhibited Aurora-A kinase with IC values of 0.78 µM (4.70-fold) and 1.12 µM (2.84-fold), respectively, as compared to alisertib (IC = 3.36 µM)...Moreover, the three-atom linkage (CHNHCH) expanded compound 5h to fill the cavity. Based on current findings, it is concluded that compounds 5h and 5e with strong Aurora-A kinase suppression may be promising anticancer agents.
Journal
|
AURKA (Aurora kinase A) • ANXA5 (Annexin A5)
|
imatinib • alisertib (MLN8237)
1year
Crosstalk of RNA methylation writers defines tumor microenvironment and alisertib resistance in breast cancer. (PubMed, Front Endocrinol (Lausanne))
RMW_Score could function as a robust biomarker for predicting BC patient survival and therapeutic benefits. This research revealed a potential TCP1 role regarding alisertib resistance in BC, providing new sights into more effective therapeutic plans.
Journal • IO biomarker
|
RBM15 (RNA Binding Motif Protein 15)
|
alisertib (MLN8237)