AT-9283

Investigational

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

Structure Search

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)

HIDE SMILES / InChI

Description
Sources: http://astx.com/wp-content/uploads/2016/11/ASTX_News_2010_12_1_General_Releases.pdf
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	Potency
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567	Inhibitor 8297	3.0 nM [IC50]
Serine/threonine-protein kinase Aurora-B 28 Target ID: CHEMBL2185 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567	Inhibitor 8297	3.0 nM [IC50]
Glycogen synthase kinase-3 beta 51 Target ID: CHEMBL262 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567	Inhibitor 8297	1.0 nM [IC50]
Tyrosine-protein kinase JAK3 27 Target ID: CHEMBL2148 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567	Inhibitor 8297	1.1 nM [IC50]
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567	Inhibitor 8297	1.2 nM [IC50]
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19143567	Inhibitor 8297	4.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT01145989	Primary		Phase II 1132	Unknown Approved Use Unknown
Leukemia 87 Sources: https://clinicaltrials.gov/ct2/show/NCT00522990	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	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	Analyte	Population
1653 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/28177130	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/28177130	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/28177130	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/28177130	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

T_1/2

Value	Dose	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

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY100652	https://www.001chemical.com/chem/search?q=DY100652
1PlusChem LLC	1P0036PX	https://www.1pchem.com/search?query=1P0036PX
AK Scientific	SYN1011	https://aksci.com/item_detail.php?cat=SYN1011
AK Scientific	X7478	https://aksci.com/item_detail.php?cat=X7478
Alfa Chemistry	ACM896466049	http://www.alfa-chemistry.com/search.aspx?q=ACM896466049
Ambeed	A335492	http://www.ambeed.com/search/Search.html?keyword=A335492
Angene	AGN-PC-0OM67P	http://www.angenechemical.com/productshow/AGN-PC-0OM67P.html
Angene	AGN-PC-0VPCN6	http://www.angenechemical.com/productshow/AGN-PC-0VPCN6.html
Angene	AGN-PC-0VPCPR	http://www.angenechemical.com/productshow/AGN-PC-0VPCPR.html
ApexBio Technology	A4117	https://www.apexbt.com/catalogsearch/result/?q=A4117
AstaTech	F17373	http://astatechinc.com/CPSResult.php?CRNO=F17373
Axon MedChem	2219	https://www.axonmedchem.com/product/2219
BLD Pharm	BD211351	http://www.bldpharm.com/search/Search.html?keyword=BD211351
BOC Sciences	896466-04-9	http://www.bocsci.com/description.asp?cas=896466-04-9
BioSynth	J-504568	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-504568
Cayman Chemical	11496	http://www.caymanchem.com/app/template/Product.vm/catalog/11496
Chem Scene	CS-0107	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0107
ChemShuttle	101296	https://www.chemshuttle.com/catalogsearch/result/?q=101296
ChemShuttle	109726	https://www.chemshuttle.com/catalogsearch/result/?q=109726
Debye Scientific	DB-078462	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-078462
Excenen	EX-A201	http://www.excenen.com/searchresultlist.php?id=EX-A201-1
Excenen	EX-A201-1	http://www.excenen.com/searchresultlist.php?id=EX-A201-1
KeyOrganics	AS-16186	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16186
Lab Network	LN00199079	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00199079
Matrix Scientific	96393	http://www.matrixscientific.com/096393.html
Matrix Scientific	146644	http://www.matrixscientific.com/146644.html
MedChem Express	HY-50514	https://www.medchemexpress.com/search.html?q=HY-50514&ft=&fa=&fp=
MolPort	MolPort-009-679-504	https://www.molport.com/shop/molecule-link/MolPort-009-679-504
MolPort	MolPort-042-665-837	https://www.molport.com/shop/molecule-link/MolPort-042-665-837
Molcore	MC100652	http://www.molcore.com/CatMC100652.html
MuseChem	I003121	https://www.musechem.com/product/I003121.html
MuseChem	I003127	https://www.musechem.com/product/I003127.html
Ryan Scientific	101-94178	https://ryansci.com/products?q=101-94178&list_q=&search_type=exact
ShangHai Biochempartner	BCP000077	http://www.biochempartner.com/search_BCP000077
ShangHai Biochempartner	BCP01732	http://www.biochempartner.com/search_BCP01732
ShangHai Biochempartner	BCP11714	http://www.biochempartner.com/search_BCP11714
eMolecules	193058184	https://orderbb.emolecules.com/search/#?query=193058184
eMolecules	31507554	https://orderbb.emolecules.com/search/#?query=31507554
eMolecules	44811823	https://orderbb.emolecules.com/search/#?query=44811823
eMolecules	50896753	https://orderbb.emolecules.com/search/#?query=50896753
eNovation Chemicals	D320068	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D320068&searchbtn.x=0&searchbtn.y=0

PubMed

Title	Date	PubMed
		252160831

Patents

Sample Use Guides

In Vivo Use Guide

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

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.

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