Biological Activity

Bioactivity / Mechanism

AMG900 reduced Aurora A, Aurora B and histone H3 phosphorylation relative to total protein in K562 and K562/IR cells after 2 days at 100–300 nM. These cellular readouts support Aurora-pathway inhibition; they do not measure biochemical affinity or Aurora C inhibition. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target	Activity	Value
AuroraC	IC50	1nM
AuroraB	IC50	4nM
AuroraA	IC50	5nM
p38α	IC50	53nM
TYK2	IC50	220nM
JNK2	IC50	520nM
Met	IC50	550nM
Tie-2	IC50	650nM

8 targets · Scroll to view more

In Vitro Studies

In K562 and K562/IR CML cells, AMG900 reduced cell viability after 3 days at 100–500 nM compared with the figure-labeled control. No significant reduction was marked at 10 or 50 nM. These treatment concentrations are not IC50 values. [1]

AMG900 concentration response in CML cells

Cell-based study · Human CML K562 and laboratory K562/IR cells (reported TKI-resistant variant). [1]

AMG900 decreased the plotted cell-viability endpoint in both models at 100–500 nM. No significant reduction is marked at 10 or 50 nM. This is a cellular viability assay, not a biochemical IC50 determination.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Cell viability (%) relative to the figure-labeled control	Reported response Significantly reduced at 100, 300 and 500 nM in both lines; *P<0.05 versus control. No significance marked at 10 or 50 nM.	[1]

Literature-Reported Treatment Conditions

Treatment concentration: 10, 50, 100, 300 and 500 nM
Exposure duration: 3 days
Method: AMG900 alone added to K562 or K562/IR cultures; trypan blue exclusion assay.
Vehicle: Stock: DMSO; diluted in PBS before use.
Reported limits: Final solvent concentrations and solvent matching of the figure-labeled control are not specified. Salt/hydration state, lot and purity are not specified.

Methods and source locations

Compound reported in the paper: AMG 900; Compound label in the paper: AMG900

Reported effects of the paper’s AMG900 material in K562 and K562/IR cells; not validation of a current Adooq lot.

Figure 4A; Materials; Trypan blue exclusion assay; Statistical analysis

Cell viability (%) relative to the figure-labeled control: Trypan blue exclusion after 3 days; Figure 4A reports mean ± SD of 3 experiments performed in triplicate. — Figure 4A and caption; Materials and methods: Trypan blue exclusion assay; Statistical analysis

Aurora pathway phosphorylation in CML cells

Cell-based study · K562 and K562/IR cells. [1]

At 100–300 nM, AMG900 reduced phosphorylated/total Aurora A, Aurora B and histone H3 ratios in both cell lines. Ratios at 50 nM showed little or no reduction. These 2-day cellular readouts support pathway modulation but do not establish direct binding, Aurora C potency or a target-specific cause of cell death.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Phosphorylated/total Aurora A, Aurora B and histone H3 protein ratios	Reported response Lower ratios at 100–300 nM in both cell lines; little or no reduction at 50 nM. Caption significance threshold: *P<0.05.	[1]

Literature-Reported Treatment Conditions

Treatment concentration: 50, 100 and 300 nM
Exposure duration: 2 days
Method: Western blotting of phosphorylated and total Aurora A, Aurora B and histone H3; Lamin A/C internal control.
Vehicle: Stock: DMSO; diluted in PBS before use.
Reported limits: Final solvent concentrations and solvent matching of the figure-labeled control are not specified. No biochemical inhibition constant is derived.

Methods and source locations

Compound reported in the paper: AMG 900; Compound label in the paper: AMG900

Reported effects of the paper’s AMG900 material in K562 and K562/IR cells; not validation of a current Adooq lot.

Figure 4B–C; Materials; Western blot analysis; AMG900 Results; Discussion comparison of AT9283 and AMG900

Phosphorylated/total Aurora A, Aurora B and histone H3 protein ratios: Western blot and densitometry; Lamin A/C internal control; Figure 4B–C described as representative of three independent experiments. No exact fold changes extracted from bars. — Figure 4B–C and caption; Materials and methods: Western blot analysis; Results AMG900 subsection

In Vivo Studies

In COLO 205 xenograft-bearing mice, a single oral AMG 900 dose of 3.75, 7.5 or 15 mg/kg suppressed tumor and bone-marrow p-Histone H3 at 3 hours. Skin showed significant suppression only at 15 mg/kg, indicating lower sensitivity as a surrogate tissue under these conditions. This experiment measured acute target engagement rather than tumor-growth inhibition. [2]

Acute tumor and surrogate-tissue pharmacodynamics

Animal study · Female athymic nude mice bearing COLO 205 human colorectal adenocarcinoma xenografts; n=10 per treatment group. [2]

Three hours after oral AMG 900, p-Histone H3 was reduced in tumor and bone marrow at all tested doses. Skin showed significant suppression only at 15 mg/kg, limiting its use as a surrogate at lower doses. These are acute pharmacodynamic results, not evidence of tumor regression.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Suppression of p-Histone H3-positive G2M cells in tumor and bone marrow	Reported response >57% inhibition at 3.75 mg/kg; >85% at 7.5 and 15 mg/kg; P<0.0001 (Results text).	[2]
p-Histone H3-positive objects per mm² in skin	Reported response Significant suppression only at 15 mg/kg (P<0.0001); no significant suppression at 3.75 or 7.5 mg/kg.	[2]

Conditions shared by the study groups

Route: Oral
Frequency: Single administration
Treatment course: 3-hour postdose assessment
Vehicle: 2% HPMC, 1% Tween-80, pH 2.2

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Vehicle	Vehicle-treated mice; small intestine positive staining control for LSC.	Comparator for all active dose groups.	[2]
3.75 mg/kg	Vehicle-treated mice; small intestine positive staining control for LSC.	Tumor and bone marrow p-Histone H3 inhibition >57% by FCM (Results text); skin LSC response not statistically significant.	[2]
7.5 mg/kg	Vehicle-treated mice; small intestine positive staining control for LSC.	Tumor and bone marrow p-Histone H3 inhibition >85% by FCM (Results text); skin LSC response not statistically significant.	[2]
15 mg/kg	Vehicle-treated mice; small intestine positive staining control for LSC.	Tumor and bone marrow p-Histone H3 inhibition >85% by FCM; significant skin suppression by LSC (P<0.0001).	[2]

Vehicle: Model: Female athymic nude mice, approximately 14 weeks old, with established COLO 205 xenografts (~200 mm³); n=10 mice per group.; Reported limits: No chronic efficacy assessment in this experiment.

3.75 mg/kg: Model: Female athymic nude mice, approximately 14 weeks old, with established COLO 205 xenografts (~200 mm³); n=10 mice per group.; Reported limits: No chronic efficacy assessment in this experiment.

7.5 mg/kg: Model: Female athymic nude mice, approximately 14 weeks old, with established COLO 205 xenografts (~200 mm³); n=10 mice per group.; Reported limits: No chronic efficacy assessment in this experiment.

15 mg/kg: Model: Female athymic nude mice, approximately 14 weeks old, with established COLO 205 xenografts (~200 mm³); n=10 mice per group.; Reported limits: No chronic efficacy assessment in this experiment.

Methods and source locations

Compound reported in the paper: AMG 900; Compound label in the paper: AMG 900

Reported pharmacodynamics of Amgen AMG 900 in this mouse model; no lot or formulation equivalence claim.

Figures 1–2; Methods: Small molecules, animal information, COLO 205 xenografts, FCM, LSC, statistics; Results tissue-response subsection; Supplement S1

Suppression of p-Histone H3-positive G2M cells in tumor and bone marrow: FCM of DNA content and p-Histone H3; cytokeratin gating for tumor cells. n=10 mice/group; figure displays mean + SE. Thresholds taken from Results prose, not curve estimation. — Figure 1A–C and caption; Results first tissue-response subsection; FCM Methods; Supplement S1

p-Histone H3-positive objects per mm² in skin: LSC; two flank skin biopsies per mouse and three scan fields per tissue section. n=10 mice/group; figure displays mean + SE. Small intestine used as positive staining control. — Figure 2A–B and caption; Results tissue-response subsection; LSC Methods; Discussion skin sensitivity

Vehicle · Methods: Small molecules; Animal and cell line information; COLO 205 tumor xenografts; Figures 1–2 and Results tissue-response subsection

3.75 mg/kg · Methods: Small molecules; Animal and cell line information; COLO 205 tumor xenografts; Figures 1–2 and Results tissue-response subsection

7.5 mg/kg · Methods: Small molecules; Animal and cell line information; COLO 205 tumor xenografts; Figures 1–2 and Results tissue-response subsection

15 mg/kg · Methods: Small molecules; Animal and cell line information; COLO 205 tumor xenografts; Figures 1–2 and Results tissue-response subsection

Specifications

Manufacturer	Adooq Bioscience
Actions	Inhibitor
CAS Number	945595-80-2
Applications	Aurora Kinase inhibitor
Formula	C₂₈H₂₁N₇OS
Molecular Weight	503.6
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

Storage & Solubility

In Vitro Solubility

Reported Solubility

Solvent	Reported Solubility
DMSO	90 mg/mL (178.71 mM)
Water	Insoluble
Ethanol	Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration: 19 mg/mL
Vehicle: 1% DMSO+30% polyethylene glycol+1% Tween 80

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] Takeda T, Tsubaki M, Genno S, et al. AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor‑sensitive and ‑resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B. Oncology reports (2020). PMID: 33000229 DOI: 10.3892/or.2020.7739 Source material
[2] Juan G, Bush TL, Ma C, et al. AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues. Journal of translational medicine (2014). PMID: 25367255 DOI: 10.1186/s12967-014-0307-x Source material

Publications

1 publication citing this product

Tomoya Takeda, .et al. , Oncol Rep, 2020, August 18 PMID: 33000229

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AMG 900

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AMG 900 1 mg

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Biological Activity

Bioactivity / Mechanism

Target & Activity

In Vitro Studies

AMG900 concentration response in CML cells

Literature-Reported Treatment Conditions

Aurora pathway phosphorylation in CML cells

Literature-Reported Treatment Conditions

In Vivo Studies

Acute tumor and surrogate-tissue pharmacodynamics

Conditions shared by the study groups

Specifications

Storage & Solubility

In Vitro Solubility

Reported Solubility

Preparing Stock Solutions

In Vivo Preparation

Storage

Research References

Publications

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