AT9283

Cas No.:	896466-04-9
Chemical Name:	1-Cyclopropyl-3-(3-(5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)urea
Synonyms:	1-Cyclopropyl-3-(3-(5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)urea;1-cyclopropyl-3-[(3Z)-3-[5-(morpholin-4-ylmethyl)benzimidazol-2-ylidene]-1,2-dihydropyrazol-4-yl]urea;AT9283;AT-9283;AT-9283,AT 9283;AT 9283;XAV9KYN9WL;1-Cyclopropyl-3-{3-[5-(Morpholin-4-Ylmethyl)-1h-Benzimidazol-2-Yl]-1h-Pyrazol-4-Yl}urea;C19H23N7O2;1-cyclopropyl-3-(3-(6-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)urea;1-cyclopropyl-3-[3-[5-(4-morpholinylmethyl)-2-benzimidazolylidene]-1,2-dihydropyrazol-4-yl]urea;35R;MLS006011044;GTPL7949
SMILES:	O1C([H])([H])C([H])([H])N(C([H])([H])C2C([H])=C([H])C3=C(C=2[H])N([H])C(C2=C(C([H])=NN2[H])N([H])C(N([H])C2([H])C([H])([H])C2([H])[H])=O)=N3)C([H])([H])C1([H])[H]
Formula:	C19H23N7O2
M.Wt:	381.4316
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	AT9283 is a multitargeted kinase inhibitor which potently inhibits aurora kinase A/B, JAK2/3 (IC50=1.2 nM, 1.1 nM).
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[1]. AT9283 (15 mg/kg) and docetaxel (10 mg/kg) alone has modest anti-tumor activity. T9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrate a statistically significant tumor growth inhibition and enhance survival inmouse xenograft model of mantle cell lymphoma[2]. AT9283 (45 mg/kg, i.p.) inhibits tumor growth in mice. Two cycles of AT9283 45 mg/kg 14 hours after drug administration confirm decreased expression of phospho-Histone H3 and Aurora B in treated animals[3].
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]. AT9283 induces apoptosis in a dose and time dependent manner and inhibits cell proliferation with an IC50 < 1 μM in B-NHL cell lines[2]. AT9283 inhibits growth, induces dose dependent cytotoxicity, and inhibits STAT3 signaling pathway in MM cell lines. T9283 inhibits phospho Histone H3 and phospho Aurora A at Thr 288. AT9283 increases G2/M phase and induces apoptosis of MM cells in a time-dependent manner[3].