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Details

Stereochemistry ACHIRAL
Molecular Formula C19H23N7O2
Molecular Weight 381.4324
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AT-9283

SMILES

c1cc2c(cc1CN3CCOCC3)nc(-c4c(c[nH]n4)NC(=NC5CC5)O)[nH]2

InChI

InChIKey=LOLPPWBBNUVNQZ-UHFFFAOYSA-N
InChI=1S/C19H23N7O2/c27-19(21-13-2-3-13)24-16-10-20-25-17(16)18-22-14-4-1-12(9-15(14)23-18)11-26-5-7-28-8-6-26/h1,4,9-10,13H,2-3,5-8,11H2,(H,20,25)(H,22,23)(H2,21,24,27)

HIDE SMILES / InChI

Molecular Formula C19H23N7O2
Molecular Weight 381.4324
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB05169 https://www.ncbi.nlm.nih.gov/pubmed/21154126

AT-9283 was being developed by Astex Pharmaceuticals as a treatment for cancer and myelofibrosis. AT-9283 is an inhibitor of mitosis (cell division) and is the second most progressed drug candidate in the Astex portfolio of novel molecularly targeted cancer drugs. All of Astex’s current products have been discovered internally using its proprietary drug discovery approach. AT9283 is a potent inhibitor of the Aurora A and B kinases and has been shown to arrest tumour growth in a range of tumour models. Aurora kinases play a key role in mitotic checkpoint control in cell division. Both Aurora A and B are over-expressed in many human tumours and are believed to be excellent targets for anti-cancer therapy.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
19.1 ng/mL
6 mg/m² 72 times / hour multiple, intravenous
dose: 6 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
25.4 ng/mL
9 mg/m² 72 times / hour multiple, intravenous
dose: 9 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.7 ng/mL
1.5 mg/m² 72 times / hour multiple, intravenous
dose: 1.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
42.9 ng/mL
13 mg/m² 72 times / hour multiple, intravenous
dose: 13 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1653 ng × h/mL
51.3 mg 72 times / hour multiple, intravenous
dose: 51.3 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
20956 ng × h/mL
567 mg 72 times / hour multiple, intravenous
dose: 567 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1200 ng × h/mL
6 mg/m² 72 times / hour multiple, intravenous
dose: 6 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1720 ng × h/mL
9 mg/m² 72 times / hour multiple, intravenous
dose: 9 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
278 ng × h/mL
1.5 mg/m² 72 times / hour multiple, intravenous
dose: 1.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2910 ng × h/mL
13 mg/m² 72 times / hour multiple, intravenous
dose: 13 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2984 ng × h/mL
67.7 mg 72 times / hour multiple, intravenous
dose: 67.7 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
38254 ng × h/mL
500 mg 72 times / hour multiple, intravenous
dose: 500 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.6 h
6 mg/m² 72 times / hour multiple, intravenous
dose: 6 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.8 h
9 mg/m² 72 times / hour multiple, intravenous
dose: 9 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13.4 h
1.5 mg/m² 72 times / hour multiple, intravenous
dose: 1.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.5 h
13 mg/m² 72 times / hour multiple, intravenous
dose: 13 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
AT-9283 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

Starting dose will be 40 mg/m2/day OR 30 mg/m2/day to be confirmed at registration. IV 24 hour continuous infusion Days 1 and 8 every three weeks
Route of Administration: Intravenous
AT-9283 leads to a clear polyploid phenotype by inhibiting the activity of Aurora B kinase in HCT116 cells with IC50 of 30 nM. Furthermore, AT-9283 also produces the potent inhibition on HCT116 colony formation.
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:48:33 UTC 2021
Edited
by admin
on Sat Jun 26 08:48:33 UTC 2021
Record UNII
XAV9KYN9WL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AT-9283
Common Name English
AT 9283 [WHO-DD]
Common Name English
UREA, N-CYCLOPROPYL-N'-(3-(6-(4-MORPHOLINYLMETHYL)-1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOL-4-YL)-
Systematic Name English
AT9283
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 291809
Created by admin on Sat Jun 26 08:48:33 UTC 2021 , Edited by admin on Sat Jun 26 08:48:33 UTC 2021
Code System Code Type Description
PUBCHEM
135398495
Created by admin on Sat Jun 26 08:48:33 UTC 2021 , Edited by admin on Sat Jun 26 08:48:33 UTC 2021
PRIMARY
FDA UNII
XAV9KYN9WL
Created by admin on Sat Jun 26 08:48:33 UTC 2021 , Edited by admin on Sat Jun 26 08:48:33 UTC 2021
PRIMARY
ChEMBL
CHEMBL495727
Created by admin on Sat Jun 26 08:48:33 UTC 2021 , Edited by admin on Sat Jun 26 08:48:33 UTC 2021
PRIMARY
DRUG BANK
DB05169
Created by admin on Sat Jun 26 08:48:33 UTC 2021 , Edited by admin on Sat Jun 26 08:48:33 UTC 2021
PRIMARY
CAS
896466-04-9
Created by admin on Sat Jun 26 08:48:33 UTC 2021 , Edited by admin on Sat Jun 26 08:48:33 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY