AMG 900 / Amgen - LARVOL DELTA

Massive scale phenotypic screening using generative chemogenomics repurposes safe drugs and discovers new drugs for intercepting early-stage lung adenocarcinoma progression (AACR 2025) - "We showed that in vitro profiling data coupled with patient profiling found the Aurora kinase inhibitor AMG900 as an interceptor of tumor invasion and progression in early-stage lung adenocarcinoma (esLUAD)... AI-driven phenotypic screening can bridge the gap between billions of drug-like molecules and patient-derived prognostic clinical signatures. By effectively removing many physical and cost constraints, we identified new active molecules through a comprehensive in silico search of the medicinal chemistry space."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Exploring common genomic biomarkers to disclose common drugs for the treatment of colorectal cancer and hepatocellular carcinoma with type-2 diabetes through transcriptomics analysis. (PubMed, PLoS One) - "Finally, cGBs-guided seven candidate drugs (Digitoxin, Camptosar, AMG-900, Imatinib, Irinotecan, Midostaurin, and Linsitinib) as the common treatment against T2D, CRC and HCC were identified through molecular docking, cross-validation, and ADME/T (Absorption-Distribution-Metabolism-Excretion-Toxicity) analysis. Most of these findings received support by the literature review of diseases specific individual studies. Thus, this study offers valuable insights for researchers and clinicians to improve the diagnosis and treatment of CRC and/or HCC patients during the co-occurrence of T2D."

Biomarker • Journal • Colorectal Cancer • Diabetes • Hepatocellular Cancer • Hepatology • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • CXCL1 • FOXC1 • GATA2 • IL6 • MIR195 • MIR34A • MMP9 • SPP1

Identification of Hub of the Hub-Genes From Different Individual Studies for Early Diagnosis, Prognosis, and Therapies of Breast Cancer. (PubMed, Bioinform Biol Insights) - "Finally, we suggested hHubGs-guided top-ranked 10 candidate drug molecules (SORAFENIB, AMG-900, CHEMBL1765740, ENTRECTINIB, MK-6592, YM201636, masitinib, GSK2126458, TG-02, and PAZOPANIB) by molecular docking analysis for the treatment against BC. The literature review also supported our findings much more for BC compared with the results of individual studies. Therefore, the findings of this study may be useful resources for early diagnosis, prognosis, and therapies of BC."

Journal • Breast Cancer • Oncology • Solid Tumor • CCNA2 • CCNB1 • CCND1 • CDK1 • EGFR • ER • TOP2A • TP53

The construction of a prognostic model by apoptosis-related genes to predict survival, immune landscape, and medication in cholangiocarcinoma. (PubMed, Clin Res Hepatol Gastroenterol) - "Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • MAP3K1

The inhibition of Aurora A kinase regulates phospholipid remodeling by upregulating LPCAT1 in glioblastoma. (PubMed, Neoplasma) - "Notably, the inhibition of Aurora A kinase by shRNA knockdown and treatment with Aurora A kinase inhibitors such as Alisertib, AMG900, or AT9283 upregulated LPCAT1 mRNA and protein expression in vitro. Aurora A kinase inhibition increased LPCAT1 expression and suppressed GBM cell proliferation. The combination of Aurora kinase inhibition with LPCAT1 inhibition may exert promising synergistic effects on GBM."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Metabolic Disorders • Oncology • Solid Tumor • AURKA • LPCAT1 • LPCAT4

2-Phenoxy-3, 4'-bipyridine derivatives inhibit AURKB-dependent mitotic processes by disrupting its localization. (PubMed, Eur J Med Chem) - "Hierarchical clustering of cell fitness profiles reveals that these compounds cluster with each other, rather than with known AURK inhibitors such as AMG900 and VX-680. The discovery and optimization of compounds that disrupt AURKB localization are successfully facilitated by MIPS. Our findings suggest that 2-phenoxy-3, 4'-bipyridine derivatives have the potential to be further developed as effective therapeutics for the treatment of malignancy by delocalizing AURKB."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKB

The Aurora kinases are a potential therapeutic target in Ewing sarcoma (AACR 2022) - "AMG900 was the most potent inhibitor in TC32 cells (Table 1) and decreased viable cell number of patient derived cultures (n=5, p<0.01)...Inhibitors of these kinases reduce viable cell number of both ES cell lines and patient derived cultures. We are currently investigating the mechanism of action."

Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • AURKA • AURKB • MYC

[VIRTUAL] Blockade of beta-catenin pathway combined with Aurora kinase activity inhibition enhances antitumor effects in adrenocortical cancer cells (AACR 2021) - "The overall survival of patients diagnosed with ACC is very low and current treatment for metastatic stages remain limited to mitotane, which has low efficiency in advanced stages of the disease and is associated with high toxicity and side effects...We studied the in vitro effects of AMG 900, an aurora kinase activity inhibitor and PNU-74654, a beta-catenin pathway blocker, in proliferation, migration, colony establishment and invasion of NCI-H295 and SW-13 ACC cell lines...On the other hand, PNU-74654 was more effective in decreasing cortisol secretion. Taken together, our data suggest that inhibition of aurora kinases activity combined with blockade of the beta-catenin pathway could bring new approaches for designing new drugs to treat certain ACCs."

Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • AURKA

Inhibition of Aurora kinase A activity enhances the antitumor response of beta- catenin blockade in human adrenocortical cancer cells. (PubMed, Mol Cell Endocrinol) - "The overall survival of patients diagnosed with ACC is low and treatment for metastatic stages remain limited to mitotane, which has low efficiency in advanced stages of the disease and is associated with high toxicity...We studied the combinatorial effects of AMG 900, an aurora kinase inhibitor and PNU-74654, a beta-catenin pathway blocker, on proliferation, survival and tumor progression in multiple ACC cell lines: NCI-H295, CU-ACC1 and CU-ACC2...In contrast, PNU-74654 was more effective in decreasing cortisol secretion. These data suggest that inhibition of aurora kinases activity combined with blockade of the beta-catenin pathway may provide a combinatorial approach for targeting ACC tumors."

Journal • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • AURKA

Aurora kinase: A target modulating invasiveness of lung adenocarcinoma (AACR 2018) - "We used two potent aurora kinase inhibitors AMG 900 and PF-03814735 to determine the effect of aurora kinase inhibition on invasiveness of LUAD cells. Here, we have identified a robust gene signature that distinguishes invasive to indolent non-invasive early-stage LUADs, which may lead to development of assays on clinical specimens such as biopsy to identify patients at high risk of developing invasive LUAD at an early stage. This gene signature also suggests Aur-A and B promote invasiveness in early stage LUAD. Our in vitro functional data suggest that targeting Aur-A and B could be a promising approach for management of early stage LUAD patients who are more likely to develop an invasive tumor."

Non Small Cell Lung Cancer

AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor‑sensitive and ‑resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B. (PubMed, Oncol Rep) - "Imatinib is the gold standard in the conventional treatment of chronic myeloid leukemia (CML)...To overcome this resistance, second‑generation (dasatinib, nilotinib, and bosutinib) and third‑generation (ponatinib) tyrosine kinase inhibitors (TKIs) have been developed and have been shown to be effective against refractory CML...In addition, we found that AMG900, a selective Aurora A and Aurora B inhibitor, increased the G2/M phase cell population and induced apoptosis via inhibition of Aurora A and Aurora B in both TKI‑sensitive and TKI‑resistant CML cells. Our studies show that Aurora A and Aurora B are promising therapeutic targets for TKI‑sensitive and TKI‑resistant CML, and AT9283 may have potential clinical applications for the treatment of TKI‑resistant CML patients."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • STAT3

AMG900 as novel inhibitor of the translationally controlled tumor protein. (PubMed, Chem Biol Interact) - "AMG900 may serve as novel lead compound for the development of differentiation therapy approaches against cancer."

Journal • Oncology

First-in-human study of AMG 900, an oral pan-Aurora kinase inhibitor, in adult patients (pts) with advanced solid tumors (ASCO 2012) - Presentation time: Saturday June 2, 1:15 PM to 5:15 PM; P=NA, N=19; Preliminary PK showed no obvious departures from dose-proportionality with a half-life of ~16 h; Tumor-response data were available for 17 pts: stable disease, 13 pts (range 0.4 to 43.7 wks); progressive disease, 4 pts. One pt (16 mg cohort) with recurrent ovarian cancer had 16% tumor shrinkage and 45% decrease in CA-125 (SD > 6 months)

Clinical data • Oncology

First-in-human study of AMG 900, an oral pan-Aurora kinase inhibitor, in adult patients (pts) with advanced solid tumors (ASCO 2012) - Presentation time: Sat, Jun 2, 1:15 PM - 5:15 PM; Anticipated presentation at ASCO 2012

Anticipated data presentation • Oncology

A phase 1 first-in-human study evaluating AMG 900 in advanced solid tumors (clinicaltrials.gov) - P1, N=92; Recruiting; Completion date: Dec ’12 → Jun ’13

Completion date • Trial delayed • Oncology