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Details

Stereochemistry ACHIRAL
Molecular Formula C28H21N7OS
Molecular Weight 503.5798
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMG-900

SMILES

Cc1cc(-c2c3ccccc3c(Nc4ccc(cc4)Oc5c(cccn5)-c6cc[nH]c(=N)n6)nn2)sc1

InChI

InChIKey=IVUGFMLRJOCGAS-UHFFFAOYSA-N
InChI=1S/C28H21N7OS/c1-17-15-24(37-16-17)25-20-5-2-3-6-21(20)26(35-34-25)32-18-8-10-19(11-9-18)36-27-22(7-4-13-30-27)23-12-14-31-28(29)33-23/h2-16H,1H3,(H,32,35)(H2,29,31,33)

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25970324

Amgen is developing AMG-900, an orally active, small molecule aurora kinase A, B and C inhibitor for the treatment of solid tumours and haematological malignancies. In tumor cells, AMG-900 inhibited autophosphorylation of aurora-A and -B as well as phosphorylation of histone H3 on Ser(10), a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG-900 treatment was aborted cell division without a prolonged mitotic arrest, which ultimately resulted in cell death. AMG-900 inhibited the proliferation of 26 tumor cell lines, including cell lines resistant to the antimitotic drug paclitaxel and to other aurora kinase inhibitors (AZD1152, MK-0457, and PHA-739358), at low nanomolar concentrations. Furthermore, AMG-900 was active in an AZD1152-resistant HCT116 variant cell line that harbors an aurora-B mutation (W221L). Oral administration of AMG-900 blocked the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. Importantly, AMG-900 was broadly active in multiple xenograft models, including 3 multidrug-resistant xenograft models, representing 5 tumor types. AMG-900 has entered clinical evaluation in adult patients with advanced cancers and has the potential to treat tumors refractory to anticancer drugs such as the taxanes.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3670 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
951 ng/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
989 ng/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10200 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FASTED
2740 ng × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2770 ng × h/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.2 h
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMG-900 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines.
2010 Dec 1
Patents

Sample Use Guides

Mice: Mice bearing established HCT116 tumors were orally administered vehicle alone or AMG-900 at 3.75, 7.5, or 15 mg/kg twice daily (b.i.d.) for 2 consecutive days per week for 3 weeks
Route of Administration: Oral
Treatment of HCT116 cells with 50 nmol/L of AMG-900 for 48 hours resulted in polyploidy and suppressed the formation of colonies after cell replating
Name Type Language
AMG-900
Common Name English
AMG900
Code English
1-PHTHALAZINAMINE, N-(4-((3-(2-AMINO-4-PYRIMIDINYL)-2-PYRIDINYL)OXY)PHENYL)-4-(4-METHYL-2-THIENYL)-
Systematic Name English
AMG 900 [WHO-DD]
Common Name English
Code System Code Type Description
FDA UNII
9R2G075611
Created by admin on Sat Jun 26 10:48:39 UTC 2021 , Edited by admin on Sat Jun 26 10:48:39 UTC 2021
PRIMARY
CAS
945595-80-2
Created by admin on Sat Jun 26 10:48:39 UTC 2021 , Edited by admin on Sat Jun 26 10:48:39 UTC 2021
PRIMARY
PUBCHEM
24856041
Created by admin on Sat Jun 26 10:48:39 UTC 2021 , Edited by admin on Sat Jun 26 10:48:39 UTC 2021
PRIMARY
EPA CompTox
945595-80-2
Created by admin on Sat Jun 26 10:48:39 UTC 2021 , Edited by admin on Sat Jun 26 10:48:39 UTC 2021
PRIMARY
ChEMBL
CHEMBL2140408
Created by admin on Sat Jun 26 10:48:39 UTC 2021 , Edited by admin on Sat Jun 26 10:48:39 UTC 2021
PRIMARY