NAV

AT9283

Identification

Generic Name
AT9283
DrugBank Accession Number
DB05169
Background

AT9283 is an aurora Kinase inhibitor developed by Astex Therapeutics for the treatment of cancer. It was discovered and developed internally using Astex’s fragment-based drug discovery platform, Pyramid.

Type
Small Molecule
Groups
Investigational
Structure
 3D
Similar Structures
Weight
Average: 381.44
Monoisotopic: 381.191323009
Chemical Formula
C19H23N7O2
Synonyms
  • 1-Cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea
External IDs
  • AT 9283
  • AT9283

Pharmacology

Indication

Investigated for use/treatment in cancer/tumors (unspecified), leukemia (myeloid), and solid tumors.

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Pharmacodynamics

Not Available

Mechanism of action

AT9283 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.

Target Actions Organism
UAurora kinase A Not Available Humans
UAurora kinase B Not Available Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

新陈代谢
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
XAV9KYN9WL
CAS number
896466-04-9
InChI Key
LOLPPWBBNUVNQZ-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N'-cyclopropyl-N-(3-{5-[(morpholin-4-yl)methyl]-1H-1,3-benzodiazol-2-yl}-1H-pyrazol-4-yl)carbamimidic acid
SMILES
OC(NC1=CNN=C1C1=NC2=C(N1)C=CC(CN1CCOCC1)=C2)=NC1CC1

References

一般References
  1. Sun L, Li D, Dong X, Yu H, Dong JT, Zhang C, Lu X, Zhou J: Small-molecule inhibition of Aurora kinases triggers spindle checkpoint-independent apoptosis in cancer cells. Biochem Pharmacol. 2008 Mar 1;75(5):1027-34. doi: 10.1016/j.bcp.2007.11.007. Epub 2007 Nov 22. [Article]
Human Metabolome Database
HMDB0248690
PubChem Substance
347909996
ChemSpider
21437042
BindingDB
50243388
ChEMBL
CHEMBL495727
ZINC
ZINC000038995988
PDBe Ligand
35R
Wikipedia
Aurora_inhibitors
PDB项
4qmm/5n23/5ut0/5wim/6cpg/6d2i

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
2 Completed Treatment Multiple Myeloma (MM) 1
1 Completed Treatment Leukemias 1
1 Completed Treatment Non-Hodgkin's Lymphoma (NHL)/Non-Hodgkin's Lymphomas/Unspecified Adult Solid Tumor, Protocol Specific 1
1 Completed Treatment Unspecified Childhood Solid Tumor, Protocol Specific 1
1, 2 Terminated Treatment Acute Lymphoblastic Leukaemias (ALL)/Acute Myeloid Leukemia/Chronic Myelogenous Leukemia (CML)/Myelodysplastic Syndrome/Myelofibrosis 1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Property Value Source
Water Solubility 0.0652 mg/mL ALOGPS
logP 1.9 ALOGPS
logP 0.48 Chemaxon
logS -3.8 ALOGPS
pKa (Strongest Acidic) 5.29 Chemaxon
pKa (Strongest Basic) 6.82 Chemaxon
Physiological Charge 0 Chemaxon
Hydrogen Acceptor Count 7 Chemaxon
Hydrogen Donor Count 4 Chemaxon
Polar Surface Area 114.45 Å2 Chemaxon
Rotatable Bond Count 5 Chemaxon
Refractivity 117.17 m3·mol-1 Chemaxon
Polarizability 41.61 Å3 Chemaxon
Number of Rings 5 Chemaxon
Bioavailability 1 Chemaxon
Rule of Five Yes Chemaxon
Ghose Filter Yes Chemaxon
Veber's Rule No Chemaxon
MDDR-like Rule No Chemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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Details 1.Aurora kinase A
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role i...
Gene Name
AURKA
Uniprot ID
O14965
Uniprot Name
Aurora kinase A
分子量
45809.03 Da
Details 2.Aurora kinase B
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in...
Gene Name
AURKB
Uniprot ID
Q96GD4
Uniprot Name
Aurora kinase B
分子量
39310.195 Da

Drug created at October 21, 2007 22:24 / Updated at November 18, 2022 07:07