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AMG-900 Aurora Kinase inhibitor

Name: AMG-900
Brand: Selleck Chemicals
SKU: S2719
Availability: InStock
Rating: 5 (25 reviews)

Cat.No.S2719

AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor for Aurora A/B/C with IC50 of 5 nM/4 nM /1 nM. It is >10-fold selective for Aurora kinases than p38α, Tyk2, JNK2, Met and Tie2. Phase 1.

Chemical Structure

Molecular Weight: 503.58

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.92%

99.92

Related Targets	DNA/RNA Synthesis CDK Microtubule Associated Ras HSP (HSP90) PD-1/PD-L1 Casein Kinase Rho Serine/threonin kinase eIF Chk ROCK Myc Kinesin PLK DHFR PAK PERK DYRK RUNX PP2A PFKFB AP-1 MPS1 Wee1 p21 BMI-1 LIM kinase Nur77 APC
Related Products	Alisertib (MLN8237) Barasertib-HQPA (AZD2811) Tozasertib (VX-680) ZM 447439 MLN8054 Hesperadin Danusertib (PHA-739358) MK-5108 TCS7010 (Aurora A Inhibitor I) PHA-680632 SNS-314 CCT137690 GSK1070916 CYC116 TAK-901 AZD1152(Barasertib) CCT129202 SNS-314 Mesylate LY3295668 SP-96

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Activity Description	PMID
SJ-GBM2	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
LAN-5	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
A673	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
DAOY	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
SK-N-SH	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	503.58	Formula	C₂₈H₂₁N₇OS	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	945595-80-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=CSC(=C1)C2=NN=C(C3=CC=CC=C32)NC4=CC=C(C=C4)OC5=C(C=CC=N5)C6=NC(=NC=C6)N

Solubility

In vitro
Batch:

DMSO : 100 mg/mL ( (198.57 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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% DMSO + % + % Tween 80 + % ddH₂O

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
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Mechanism of Action

Targets/IC₅₀/Ki	Aurora C ^[1] (Cell-free assay) 1 nM Aurora B ^[1] (Cell-free assay) 4 nM Aurora A ^[1] (Cell-free assay) 5 nM p38α ^[1] (Cell-free assay) 53 nM
In vitro	AMG 900 is a novel class of ATP-competitive phthalazinamine small molecule inhibitors of aurora kinases. In HeLa cells, AMG 900 inhibits autophosphorylation of aurora-A and -B as well as phosphorylation of histone H3 on Ser, a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG 900 treatment is aborted cell division without a prolonged mitotic arrest, which ultimately results in cell death. AMG 900 inhibits the proliferation of 26 tumor cell lines, including cell lines resistant and to other aurora kinase inhibitors (AZD1152, MK-0457, and PHA-739358), at low nanomolar concentrations (about 2- 3 nM). Furthermore, AMG 900 is active in an AZD1152-resistant HCT116 variant cell line that harbors an aurora-B mutation (W221L). ^[1]
Kinase Assay	Enzyme kinase assays
Kinase Assay	Recombinant GST- or His-tagged aurora-A (TPX2), and aurora-B proteins are expressed using a baculovirus system and purified by affinity chromatography. AMG 900 activity is assessed using a standardized homogenous time-resolved fluorescence (HTRF) assay. Enzyme assays for 24 other kinases (aurora-C, p38α, TYK2, JNK2, JAK3, c-Met, VEGFR2, p38β, TIE-2, ABL (T315I), ERK1, BTK, JNK3, CDK5, PKAα, JNK1, p70S6K, PKBα, MSK1, LCK, SRC, IGFR, JAK2, and c-KIT) are done internally in a similar manner. Concentrations of enzyme, peptide substrate, and ATP in the reaction are optimized depending on the specific activity of the kinase and measured K_m values for their corresponding substrates. AMG 900 is evaluated in a kinome competition binding assay (n = 353 unique kinases) by Ambit Biosciences. AMG 900 is initially screened at a single concentration of 1000 nM, and quantitative binding constants (Kd) are determined for each positive hit (< 20 percentage of control).
In vivo	Oral administration of AMG 900 blocks the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. AMG 900 is broadly active in multiple xenograft models, including 3 multidrugresistant xenograft models, representing 5 tumor types. ^[1] AMG 900 exhibits a low-to-moderate clearance and a small volume of distribution. Its terminal elimination half-life ranged from 0.6 to 2.4 hours. AMG 900 is well-absorbed in fasted animals with an oral bioavailability of 31% to 107%. Food intake has an effect on rate (rats) or extent (dogs) of AMG 900 oral absorption. The clearance and volume of distribution at steady state in humans are predicted to be 27.3 mL/h/kg and 93.9 mL/kg, respectively. AMG 900 exhibits acceptable PK properties in preclinical species and is predicted to have low clearance in humans. ^[2]
References	https://pubmed.ncbi.nlm.nih.gov/20935223/ https://pubmed.ncbi.nlm.nih.gov/21294625/

Applications

Methods	Biomarkers	Images	PMID
Western blot	phosphorylated aurora A-C / Aurora A / Aurora C Cyclin D1 / Cyclin A / Cyclin B1 / p53 / p21		24989836
Growth inhibition assay	Cell number		30221846

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01380756	Completed	Cancer\|Hematologic Malignancies\|Leukemia\|Myeloid Leukemia	Amgen	October 4 2011	Phase 1
NCT00858377	Completed	Advanced Malignancy\|Advanced Solid Tumors\|Cancer\|Solid Tumors\|Tumors	Amgen	August 10 2009	Phase 1

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