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

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

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	Inhibitor 8,504	3.0 nM [IC50]
Serine/threonine-protein kinase Aurora-B 28	Inhibitor 8,504	3.0 nM [IC50]
Glycogen synthase kinase-3 beta 52	Inhibitor 8,504	1.0 nM [IC50]
Tyrosine-protein kinase JAK3 28	Inhibitor 8,504	1.1 nM [IC50]
Tyrosine-protein kinase JAK2 59	Inhibitor 8,504	1.2 nM [IC50]
Tyrosine-protein kinase ABL 29	Inhibitor 8,504	4.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple myeloma 159	Primary		Phase II 1,147	Unknown
Leukemia 72	Primary		Phase II 1,147	Unknown

C_max

Value	Dose	Analyte	Population
19.1 ng/mL	6 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
42.9 ng/mL	13 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
25.4 ng/mL	9 mg/m² 1 times / day multiple, intravenous	AT-9283 plasma	Homo sapiens
4.7 ng/mL	1.5 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
1200 ng × h/mL	6 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
2910 ng × h/mL	13 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
1720 ng × h/mL	9 mg/m² 1 times / day multiple, intravenous	AT-9283 plasma	Homo sapiens
278 ng × h/mL	1.5 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
38254 ng × h/mL	500 mg 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
20956 ng × h/mL	567 mg 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
1653 ng × h/mL	51.3 mg 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
2984 ng × h/mL	67.7 mg 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
7.6 h	6 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
7.5 h	13 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens
7.8 h	9 mg/m² 1 times / day multiple, intravenous	AT-9283 plasma	Homo sapiens
13.4 h	1.5 mg/m² 72 times / hour multiple, intravenous	AT-9283 plasma	Homo sapiens

Sourcing

Sourcing

Show entries

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

Showing 1 to 5 of 41 entries

Previous1 2 3 4 5…9Next

PubMed

Title	Date	PubMed
No data available in table

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.

Show entries

Name

Type

Language

AT-9283

Common Name

English

UREA, N-CYCLOPROPYL-N'-(3-(6-(4-MORPHOLINYLMETHYL)-1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOL-4-YL)-

Preferred Name

English

AT 9283 [WHO-DD]

Common Name

English

AT9283

Code

English

Showing 1 to 4 of 4 entries

Previous1Next

Show entries

Classification Tree

Code System

Code

Designated

FDA ORPHAN DRUG

291809

Showing 1 to 1 of 1 entries

Previous1Next

Show entries

Code System

Code

Type

Description

SMS_ID

100000175099

PRIMARY

PUBCHEM

135398495

PRIMARY

FDA UNII

XAV9KYN9WL

PRIMARY

ChEMBL

CHEMBL495727

PRIMARY

DRUG BANK

DB05169

PRIMARY

Showing 1 to 5 of 8 entries

Previous1 2Next

ACTIVE MOIETY


					XAV9KYN9WL

AT-9283

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2