Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H23N7O2 |
Molecular Weight | 381.4316 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C(NC1CC1)NC2=CNN=C2C3=NC4=C(N3)C=CC(CN5CCOCC5)=C4
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)
DescriptionCurator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB05169
https://www.ncbi.nlm.nih.gov/pubmed/21154126
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567 |
3.0 nM [IC50] | ||
Target ID: CHEMBL2185 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567 |
3.0 nM [IC50] | ||
Target ID: CHEMBL262 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567 |
1.0 nM [IC50] | ||
Target ID: CHEMBL2148 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567 |
1.1 nM [IC50] | ||
Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567 |
1.2 nM [IC50] | ||
Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567 |
4.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
19.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22015452 |
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01145989
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21154126
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.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
291809
Created by
admin on Fri Dec 15 16:13:14 UTC 2023 , Edited by admin on Fri Dec 15 16:13:14 UTC 2023
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100000175099
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135398495
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XAV9KYN9WL
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CHEMBL495727
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admin on Fri Dec 15 16:13:14 UTC 2023 , Edited by admin on Fri Dec 15 16:13:14 UTC 2023
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DB05169
Created by
admin on Fri Dec 15 16:13:14 UTC 2023 , Edited by admin on Fri Dec 15 16:13:14 UTC 2023
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896466-04-9
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C66947
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DTXSID401026047
Created by
admin on Fri Dec 15 16:13:14 UTC 2023 , Edited by admin on Fri Dec 15 16:13:14 UTC 2023
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PRIMARY |
ACTIVE MOIETY