AT9283

Name: AT9283
Brand: Selleck Chemicals
SKU: S1134
Rating: 5 (13 reviews)

For research use only. Not for use in humans.

Catalog No.S1134

13 publications

Molecular Weight(MW): 381.43

AT9283 is a potent JAK2/3 inhibitor with IC50 of 1.2 nM/1.1 nM in cell-free assays; also potent to Aurora A/B, Abl(T315I). Phase 2.

Selleck's AT9283 has been cited by 13 publications

Cell Stem Cell, 2012, 11(2):179-94

PubMed: 22862944 ( click the link to review the publication )

J Clin Invest, 2018, 128(1):387-401

PubMed: 29200404 ( click the link to review the publication )

Nat Commun, 2018, 9(1):358

PubMed: 29367740 ( click the link to review the publication )

Mol Cancer Ther, 2016, 15(2):334-42

PubMed: 26772203 ( click the link to review the publication )

Gastric Cancer, 2016, 19(1):53-62

PubMed: 25407459 ( click the link to review the publication )

Cancer Lett, 2014, 354(1):68-76

PubMed: 25107642 ( click the link to review the publication )

Gastric Cancer, 2014, 10.1007/s10120-014-0444-1

PubMed: 25407459 ( click the link to review the publication )

PLoS One, 2014, 9(7):e102741

PubMed: 25048812 ( click the link to review the publication )

Cancer Res, 2013, 73(20):6310-22

PubMed: 24067506 ( click the link to review the publication )

Cancer Lett, 2013, 341(2):224-30

PubMed: 23941832 ( click the link to review the publication )

J Cell Mol Med, 2013, 17(2):265-76

PubMed: 23301855 ( click the link to review the publication )

Drug Development Reseach, 2013, 272–281

PubMed: ( click the link to review the publication )

Int J Clin Exp Pathol, 2013, 6(10):2082-91

PubMed: 24133586 ( click the link to review the publication )

3 Customer Reviews

HEL cells were treated with 0.5, 1 or 5 uM of AT9283 or left untreated for 3 hrs. The expression and phosphorylation state of STAT5 (P-STAT5) and Jak2 (P-Jak2) was assessed by Western blot immunodetection.

J Cell Mol Med 2013 17(2), 265-76. AT9283 purchased from Selleck.
AM-005 inhibits the growth of HT29 cells in vivo. The tumor volume was measured after intragastric administration of AM-005 (15 mg/kg or 25 mg/kg). The 25 mg/kg AT9283 was used as a positive control. The results are the mean tumor volume盨D for groups of n = 8.

Drug Development Reseach 2013 272-281. AT9283 purchased from Selleck.
HEL cells were treated for 3 hours with the indicated concerntrations of AT9283. AT9283 inhibitors Jak2-V617F mediated signal transduction at submicromolar concentrations in intact cells . At concentrations of 490 nm the Jak2-V617F inhibition is almost complete and has reached almost background levels (for background STAT5 phosphorylation see 4400nm)

Dr. Claude Haan and Catherine Rolvering of Universite du Luxembourg. AT9283 purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description

AT9283 is a potent JAK2/3 inhibitor with IC50 of 1.2 nM/1.1 nM in cell-free assays; also potent to Aurora A/B, Abl(T315I). Phase 2.

Targets

JAK3 ^[1] (Cell-free assay)	JAK2 ^[1] (Cell-free assay)	Aurora A ^[1] (Cell-free assay)	Aurora B ^[1] (Cell-free assay)	Abl1 (T315I) ^[1] (Cell-free assay)	View More
1.1 nM	1.2 nM	~3.0 nM	~3.0 nM	4 nM	View More

In vitro

AT9283 leads to a clear polyploid phenotype by inhibiting the activity of Aurora B kinase in HCT116 cells with IC50 of 30 nM. Furthermore, AT9283 also produces the potent inhibition on HCT116 colony formation. ^[1]

Cell Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
HCT116 cells	M1T3[WN6fG:2b4jpZ:Kh[XO\|YYm=	NVvrVldWOTBvMUSg[IF6ew>?	M{H3TGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhEXDFzNjDj[YxteyCjc4Pld5Nm\CCjczDueY1j\XJib3[gZ49td26rZYOgZYZ1\XJiMUCgeI8hOTRiZHH5d{BjgSClb3zvcpkh\m:{bXnu[{Bie3OjeTygTWM2OD1yLkCxNkDPxE1?	MkDTNVkyPDN3Nke=
HT-29 cells	NFy0UWlHfW6ldHnvckBie3OjeR?=	MmrTO\|IhcA>?	NW\tcXo4SW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gTHQuOjliY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME2wMlM5OyEQvF2=	NX;CU2hNOjN4NkSwPVk>
A549 cells	NVnTTm9KTnWwY4Tpc44h[XO\|YYm=	MUe3NkBp	MkHoRY51cXS3bX;yJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQUW0PUBk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTBwNUGyJO69VQ>?	NYDGdFBxOjN4NkSwPVk>
LoVo cells	NH[yOFdHfW6ldHnvckBie3OjeR?=	M3XRR\|czKGh?	NULqWlJkSW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUI9XdyClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUCuOVU{KM7:TR?=	MYOyN\|Y3PDB7OR?=
K562 cells	MmrTSpVv[3Srb36gZZN{[Xl?	NYjyS3N3PzJiaB?=	MYnBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCNNU[yJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:OS54IN88US=>	MWqyN\|Y3PDB7OR?=
U937 cells	MXPGeY5kfGmxbjDhd5NigQ>?	NGnnb3Q4OiCq	M{DLbWFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGW5N\|ch[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeR?=	NIPuU5ozOzZ4NEC5PS=>

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Growth inhibition assay	Cell viability; PubMed: 21430070 Clin Cancer Res AT9283 reduces MM cells viability in a dose dependent manner. Cells were treated with increasing doses of AT9283 for 72 hours and cell viability was measured by MTT assay	21430070

In vivo

In HCT116 human colon carcinoma xenograft bearing mice, AT9283 treatment (15 mg/kg and 20 mg/kg) for 16 days results in a significant tumor growth inhibition of 67% and 76%, respectively. In addition, AT9283 also exhibits a significantly longer half-life in tumors(2.5 hours) compared with plasma (0.5 hour) and modest oral bioavailability in mice (Fp.o. = 24%). ^[1]

Protocol

Kinase Assay: ^[1]	- Collapse Aurora A and Aurora B Kinase Assays: Assays for Aurora A and B are performed in a DELFIA format. Aurora A enzyme is incubated with AT9283 and 3 μM cross-tide substrate (biotin-CGPKGPGRRGRRRTSSFAEG) in 10 mM MOPS, pH 7, 0.1 mg/mL BSA, 0.001% Brij-35, 0.5% glycerol, 0.2 mM EDTA, 10 mM MgCl₂, 0.01% β-mercaptoethanol, 15 μM ATP, and 2.5% DMSO. Aurora B enzyme is incubated with AT9283, 3 μM of the above substrate in 25 mM Tris, pH 8.5, 5 mM MgCl₂, 0.1 mg/mL BSA, 0.025% Tween-20, 1 mM DTT, 15 μM ATP, and 2.5% DMSO. Reactions are allowed to proceed for 60 minutes and 45-90 minutes for Aurora A and Aurora B, respectively, before quenching with EDTA. The reaction mixtures are then transferred to a neutravidin-coated plate, and phosphorylated peptide is quantified by means of a phospho-specific antibody and a europium labeled secondary antibody using time-resolved fluorescence (excitation, 337 nm; emission, 620 nm). IC50 values for the control compounds are 92 nM (Aurora A assay) and 17 nM (Aurora B).
Cell Research: ^[1]	- Collapse Cell lines: HCT 116 cells Concentrations: 1 nM - 10 μM Incubation Time: 72 hours Method: HCT 116 cells are cultured in DMEM + 10% FBS + GLUTAMAX I. Black 96-well flat-bottomed (clear) tissue culture treated plates are seeded in 200 μL of medium and incubated for approximately 16 hours at 37°C in a humidified atmosphere of 5% CO₂ in air. Cells are treated with test compound at nine different concentrations (spanning 1 nM to 10 μM, plus DMSO vehicle control) and then incubated for 72 hours. Polyploidy morphological observations of the cells are then noted. The concentration of AT9283 required to produce a distinct polyploid phenotype is reported. Cells are seeded at a concentration of 75−100 cells/mL relevant culture media onto 6- or 24-well tissue culture plates and allowed to recover for 16 hours. Test compound (11 concentrations spanning 0.1 nM to 10 μM) or vehicle control (DMSO) is added to duplicate wells to give a final DMSO concentration of 0.1%. Following compound addition, colonies are allowed to grow between 10 and 14 days for optimum discrete colony counting. Colonies are fixed in 2 mL of Carnoys fixative (25% acetic acid, 75% MeOH) and stained in 2 mL of 0.4% w/v crystal violet. The numbers of colonies in each well is counted. IC50 values are calculated by sigmoidal dose-response (variable slope) IC50 curves using Prism Graphpad software. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: HCT116 cells are injected s.c. Into the hind flank of male BALB/c mice. Formulation: Belinostat is dissolved in 10% DMSO, 20% water, 70% hydroxypropyl- β-cyclodextrin (25% w/v aq). Dosages: 15 mg/kg and 20 mg/kg Administration: Administered via i.p. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	76 mg/mL (199.25 mM)
	Ethanol	38 mg/mL (99.62 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+ddH2O For best results, use promptly after mixing.	5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download AT9283 SDF

Molecular Weight	381.43
Formula	C₁₉H₂₃N₇O₂
CAS No.	896466-04-9
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A
Smiles	O=C(NC1CC1)NC2=C[NH]N=C2C3=NC4=CC(=CC=C4[NH]3)CN5CCOCC5

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JAK Signaling Pathway Map

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AT9283