SML2394

AT9283

≥98% (HPLC)

• Synonym(s): 1-Cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea, AT 9283, AT-9283, N-Cyclopropyl-N′-[3-[6-(4-morpholinylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]-urea
• Empirical Formula (Hill Notation): C₁₉H₂₃N₇O₂
• CAS Number: 896466-04-9
• Molecular Weight: 381.43
• MDL number: MFCD12031513
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: −20°C
• SMILES string: [nH]1nc(c(c1)NC(=O)NC5CC5)c2[nH]c3c(n2)ccc(c3)CN4CCOCC4
• 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)
• InChI key: LOLPPWBBNUVNQZ-UHFFFAOYSA-N

Description

Biochem/physiol Actions

A multitargeted kinase inhibitor with in vivo anticancer efficacy and potent activity against Abl, aurora kinase A/B and JAK2/3.

AT9283 has also been shown to accelerate growth arrest in various xenograft models.

AT9283 is an ATP site-targeting pyrazole-benzimidazole-based molecule with inhibitory potency against multiple kinases, most notably Aurora A/B (IC50 ≤3.0 nM), JAK2/3 (IC50 = 1.2/1.1 nM), Abl T315I (IC50 = 4 nM), GSK3β, FGFR2, VEGFR3 (Flt4), Mer, Ret, Rsk2/3, Tyk2, Yes (IC50 = 1-10 nM). AT9283 also inhibits 72 other kinases/mutations at a reduced potency (IC50 = 10-30 nM against 14, 30-100 nM against 21, 100-300 against 37 targets), while displaying an IC50 >300 nM toward 144 other kinase targets. AT9283 inhibits the growth/survival of multiple solid tumor cell lines in vitro (IC50 = 7.7-20 nM) and shows anti-cancer efficacy in mice via i.p. injection in vivo (67% and 76%HCT116 tumor growth inhibition on day 16, respectively, with 15 and 20 mg/kg b.i.d., two-day on and two-day off; >95% inhibition of Ba/F3 ETV6-JAK2 leukemia proliferation on day 12 with 10 mg/kg b.i.d. on days 2–5 and 8–12).

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable