| Identification | Back Directory | [Name]
AT9283 | [CAS]
896466-04-9 | [Synonyms]
CS-48
J-504568
AT9283, >=98%
AT-9283; AT 9283
N-cyclopropyl-N'-[3-[5-(4-morpholinylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]Urea
1-Cyclopropyl-3-(3-(5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)urea
Urea, N-cyclopropyl-N'-[3-[6-(4-morpholinylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]-
1-Cyclopropyl-3-(3-(5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)urea AT9283 | [Molecular Formula]
C19H23N7O2 | [MDL Number]
MFCD12031513 | [MOL File]
896466-04-9.mol | [Molecular Weight]
381.438 |
| Chemical Properties | Back Directory | [density ]
1.45 | [storage temp. ]
Keep in dark place,Inert atmosphere,2-8°C | [solubility ]
insoluble in H2O; ≥19.05 mg/mL in DMSO; ≥47.6 mg/mL in EtOH with ultrasonic | [form ]
solid | [pka]
10.58±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
AT-9283 is a broad spectrum kinase inhibitor that potently inhibits Aurora A, Aurora B, JAK2, JAK3, and c-ABL (IC50s = 3, 3, 1.2, 1.1, and 4 nM, respectively). It also potently (IC50 = <1 μM) inhibits many other kinases, including serine/threonine kinases as well as receptor and non-receptor tyrosine kinases. As Aurora kinases have roles in mitosis, inhibitors of these kinases, including AT-9283, have potential in cancer therapy. Consistent with this, AT-9283 is effective in preventing proliferation of cancer cells both in vitro and in vivo and this effect may be enhanced by combination therapy with other chemotherapeutics.[Cayman Chemical] | [Definition]
ChEBI:1-cyclopropyl-3-[3-[5-(4-morpholinylmethyl)-2-benzimidazolylidene]-1,2-dihydropyrazol-4-yl]urea is a member of benzimidazoles. | [Biological Activity]
at9283, a synthetic small heterocyclic molecule discovered using a fragment-based approach, is a novel inhibitor of aurora kinase, a family of serine/threonine kinases regulating both mitosis and meiosis, that potently inhibits aurora kinases a and b, with 50% inhibition concentration ic50 value of 3 nm, as well as janus kinases (jaks), abelson kinase (bcrabl t315i) and flt-3. at9283 has been found to be therapeutic in leukemic cells, myeloproliferative disorders and multiple solid tumor cell lines. study results have shown that at9283 exhibits anti-proliferative activity and induces polyploidy and apoptosis in aggressive b-cell nhl cell lines associated with inhibition of aurora kinase b.qi w, liu x, cooke ls, persky do, miller tp, squires m, mahadevan d. at9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive b-cell lymphomas. int j cancer. 2012 jun 15;130(12):2997-3005. doi: 10.1002/ijc.26324. epub 2011 nov 19.arkenau ht, plummer r, molife lr, olmos d, yap ta, squires m, lewis s, lock v, yule m, lyons j, calvert h, judson i. a phase i dose escalation study of at9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies. ann oncol. 2012 may;23(5):1307-13. doi: 10.1093/annonc/mdr451. epub 2011 oct 19. | [Enzyme inhibitor]
This potent JAK protein kinase inhibitor (FW = 381.43 g/mol; CAS
896466-04-9; Solubility = 76 mg/mL DMSO), also named 1-cyclopropyl-
3- (3- (5- (morpholinomethyl) -1H-benzo[d]imidazol-2-yl) -1H-pyrazol-4-
yl) urea, targets JAK3 (IC50 = 1.1 nM), JAK2 (IC50 = 1.2 nM), Aurora A
(IC50 = 3 nM), Aurora B (IC50 = 3 nM), and and Abl (T315I). | [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]. | [target]
Aurora A | [IC 50]
Aurora A: 3 nM (IC50); Aurora B: 3 nM (IC50); JAK3: 1.1 nM (IC50); JAK2: 1.2 nM (IC50); ABL(T315I): 4 nM (IC50); Flt-3 | [storage]
Store at -20°C |
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