Aurora A inhibitors(Serine/threonine-protein kinase Aurora-A inhibitors), Aurora B inhibitors(Serine/threonine-protein kinase Aurora-B inhibitors), Aurora C inhibitors(Serine/threonine-protein kinase Aurora-C inhibitors)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Advanced cancerAdvanced Malignant Solid Neoplasm

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

Amgen, Inc.

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC28H21N7OS

InChIKeyIVUGFMLRJOCGAS-UHFFFAOYSA-N

CAS Registry945595-80-2

Clinical Trials associated with AMG-900

NCT00858377

/ CompletedPhase 1

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Advanced Solid Tumors

This first-in-human study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK of oral AMG 900 in subjects with advanced solid tumors. Up to 50 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 42 subjects in three taxane-resistant tumor types. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study

Start Date10 Aug 2009

Sponsor / Collaborator

Amgen, Inc.

100 Clinical Results associated with AMG-900

100 Translational Medicine associated with AMG-900

100 Patents (Medical) associated with AMG-900

Literatures (Medical) associated with AMG-900

01 Feb 2025·Current Computer-Aided Drug Design

Discovery of Novel Pyrimidine Based Small Molecule Inhibitors as VEGFR-2 Inhibitors: Design, Synthesis, and Anti-cancer Studies

Article

Author: Dhawale, Sachin A. ; Dabhade, Pratap S. ; Mokale, Santosh N.

Background:Receptor tyrosine kinases (RTKs) are potent oncoproteins in cancer that, when mutated or overexpressed, can cause uncontrolled growth of cells, angiogenesis, and metastasis, making them significant targets for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2), is a tyrosine kinase receptor that is produced in endothelial cells and is the most crucial regulator of angiogenic factors involved in tumor angiogenesis. So, a series of new substituted N-(4-((2-aminopyrimidin-5-yl)oxy)phenyl)-N-phenyl cyclopropane- 1,1-dicarboxamide derivatives as VEGFR-2 inhibitors have been designed and synthesized.Background:Receptor tyrosine kinases (RTKs) are potent oncoproteins in cancer that, when mutated or overexpressed, can cause uncontrolled growth of cells, angiogenesis, and metastasis, making them significant targets for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2), is a tyrosine kinase receptor that is produced in endothelial cells and is the most crucial regulator of angiogenic factors involved in tumor angiogenesis. So, a series of new substituted N-(4-((2-aminopyrimidin-5-yl)oxy)phenyl)-N-phenyl cyclopropane1,1-dicarboxamide derivatives as VEGFR-2 inhibitors have been designed and synthesized.Methods:Utilizing H-NMR, C13-NMR, and mass spectroscopy, the proposed derivatives were produced and assessed. HT-29 and COLO-205 cell lines were used for the cytotoxicity tests. The effective compound was investigated further for the Vegfr-2 kinase inhibition assay, cell cycle arrest, and apoptosis. A molecular docking examination was also carried out with the Maestro-12.5v of Schrodinger.Results:In comparison to the reference drug Cabozantinib (IC50 = 9.10 and 10.66 μM), compound SP2 revealed promising cytotoxic activity (IC50 = 4.07 and 4.98 μM) against HT-29 and COLO-205, respectively. The synthesized compound SP2 showed VEGFR-2 kinase inhibition activity with (IC50 = 6.82 μM) against the reference drug, Cabozantinib (IC50 = 0.045 μM). Moreover, compound SP2 strongly induced apoptosis by arresting the cell cycle in the G1 phase. The new compounds' potent VEGFR-2 inhibitory effect was noted with key amino acids Asp1044, and Glu883, and the hydrophobic interaction was also observed in the pocket of the VEGFR-2 active site by using a docking study.Conclusion:The results demonstrate that at the cellular and enzyme levels, the synthetic compounds SP2 are similarly effective as cabozantinib. The cell cycle and apoptosis data demonstrate the effectiveness of the suggested compounds. Based on the findings of docking studies, cytotoxic effects, in vitro VEGFR-2 inhibition, apoptosis, and cell cycle arrest, this research has given us identical or more effective VEGFR-2 inhibitors.

01 Nov 2024·Journal of Molecular Liquids

Identification of Aurora A kinase allosteric inhibitors: A comprehensive virtual screening through fingerprint-based similarity search, molecular docking, machine learning and molecular dynamics simulation

Author: Sardarsinh Suryawanshi, Vikramsinh ; Chunarkar Patil, Pritee ; Pravin Pawar, Surbhi ; Abdelghani, Heba Taha M. ; Sudhir Kolpe, Mahima ; Bhowmick, Shovonlal

The Aurora A kinase (AAK) protein controls spindle assembly and promotes cell divisions in various diseases including cancer.In the present study, allosteric inhibition of AAK protein through different advanced computational screening approaches is employed to target AAK's allosteric inhibition-modulation.Precisely, extensive computational techniques including allosteric binding sites recognition of AAK protein, fingerprint-based similarity search, multi-step mol. docking through AutoDock Vina and PLANTS, and a 100 ns mol. dynamics (MD) simulations studies were carried out followed by the calculation of binding free energy with MM-GBSA based approaches, has been employed for identification of potential allosteric inhibitors-modulators of AAK protein.The study outcome highlighted that all three identified small mol. chem. entities exhibit strong binding interaction affinity in both the docking analyses at the allosteric domain of AAK protein and also greater interaction stability in comparison to the considered standard compoundIn addition, all identified three screened hits also show acceptable pharmacokinetics and medicinal chem. properties, which certainly dictates their potentiality for becoming good drug-like compounds for inhibiting-modulating the activity of AAK protein binds with similar amino acids of the allosteric domain of AAK protein with selected three compoundsAll the selected mols. were found to show an acceptable ADMET profile.Moreover, the MM-GBSA-based binding energy was found to be in the range of -8 to -35 Kcal/mol, which showed a strong association between proposed mols. and AAK protein.Comprehensive computational approach shows that the selected proposed three inhibitors of AAK protein are the best candidates as potential inhibitors.

01 Oct 2024·Clinics and Research in Hepatology and Gastroenterology

The construction of a prognostic model by apoptosis-related genes to predict survival, immune landscape, and medication in cholangiocarcinoma

Article

Author: Weng, Meiling ; Wang, Zhengfei ; Jiang, Junjie ; Shi, Yinsheng ; Xu, Pengcheng ; Rao, Linbin ; Shen, Peng

BACKGROUNDCholangiocarcinoma (CCA) is a highly aggressive and invasive malignant tumor of the bile duct, with a poor prognosis and a high mortality rate. Currently, there is a lack of effective targeted treatment methods and reliable biomarkers for prognosis.METHODSWe downloaded RNA-seq and clinical data of CCA from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as training and test sets. The apoptosis-related genes were obtained from the Molecular Signatures Database (MsigDB) database. We used univariate/multivariate Cox regression and Lasso regression analyses to construct a riskscore prognostic model. Based on the median riskscore, we clustered the patients into high-risk (HR) and low-risk (LR) groups. We carried out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) in HR and LR groups. The single sample gene set enrichment analysis (ssGSEA) was employed to analyze the immune infiltration of the HR and LR groups. The CellMiner database was utilized to predict drugs and perform molecular docking on drugs and target proteins.RESULTSWe identified 8 genes with prognostic significance to construct a prognostic model. Results of GO and KEGG demonstrated that DEGs were mainly enriched in biological functions such as fatty acid metabolic processes and pathways such as the cAMP signaling pathway. Results of ssGSEA uncovered that immune cells such as DCs and Macrophages in the HR group, as well as immune functions such as Check-point and Parainflammation, were considerably higher than those in the LR group. Drug sensitivity prediction and results of molecular docking revealed that Rigosertib targeted the prognostic genes MAP3K1. HYPOTHEMYCIN and AMG900 effectively targeted JUN.CONCLUSIONOur 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.

100 Deals associated with AMG-900

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 1	United States	Amgen, Inc.	10 Aug 2009
Advanced cancer	Phase 1	Australia	Amgen, Inc.	10 Aug 2009
Advanced Malignant Solid Neoplasm	Phase 1	Australia	Amgen, Inc.	10 Aug 2009
Advanced Malignant Solid Neoplasm	Phase 1	United States	Amgen, Inc.	10 Aug 2009

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00858377 (Pubmed \| Invest New Drugs) Manual	Phase 1	Ovarian Cancer \| Solid tumor \| Triple Negative Breast Cancer \| Prostatic Cancer HER2 Negative \| ER Negative \| PR Negative	105	AMG 900 (advanced solid tumors)	(mlnwguaule) = The MTD was 25 mg/day, increasing to 40 mg/day with G-CSF. ddbjoqbsfw (smszqupgzd ) View more	Positive	01 Dec 2018
NCT00858377 (Pubmed \| Invest New Drugs) Manual	Phase 1		105	AMG 900+G-CSF (ovarian cancer)		Positive	01 Dec 2018
NCT00858377 (AACR2016)	Phase 1	HR-positive/HER2-low Solid Tumors	105	AMG 900	rjbbtskess(erwrdwasck) = Myelotoxicities were the most common grade ? 3 treatment-related AEs zgbfbljhwj (bksteikkkw ) View more	Positive	15 Jul 2016
NCT00858377 (ASCO2016)	Phase 1	HR-positive/HER2-low Solid Tumors \| Advanced cancer	105	AMG 900	(mgexmtwzbu) = grade 4 neutropenia was the primary dose limiting toxicity of AMG 900 treatment ykmsueisjh (zwqlipvzfx ) View more	-	20 May 2016

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AMG-900

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