AST 487

• CAT Number: I004374
• CAS Number: 630124-46-8
• Molecular Formula: C26H30F3N7O2
• Molecular Weight: 529.6
• Purity: ≥95%
• Target: FLT3
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 0.88 uM
• InChI: InChI=1S/C26H30F3N7O2/c1-3-35-10-12-36(13-11-35)16-18-4-5-20(14-22(18)26(27,28)29)34-25(37)33-19-6-8-21(9-7-19)38-24-15-23(30-2)31-17-32-24/h4-9,14-15,17H,3,10-13,16H2,1-2H3,(H,30,31,32)(H2,33,34,37)
• InChIKey: ODPGGGTTYSGTGO-UHFFFAOYSA-N
• SMILES: CNC1=CC(OC2=CC=C(NC(NC3=CC=C(CN4CCN(CC)CC4)C(C(F)(F)F)=C3)=O)C=C2)=NC=N1

AST-487 (Cat No.:I004374) is an N,N’-diphenylurea, a competitive inhibitor of Flt3 with a ki value of 0.12 μM. In addition to FLT3, AST487 inhibits RET, KDR, c-KIT and c-ABL kinases with IC50 values below 1 μM.

Reference

1:Cancer Biother Radiopharm. 2003 Aug;18(4):581-8. Assessment of hepatic toxicity from treatment with 90Y-SMT 487 (OctreoTher(TM)) in patients with diffuse somatostatin receptor positive liver metastases.Bushnell D,Menda Y,Madsen M,O/’Dorisio T,Carlisle T,Zehr P,Ponto L,Karwal M,Parker S,Ponto J,Connolly M,Bouterfa H, PMID: 14503953 DOI: 10.1089/108497803322287664 Abstract: The purpose of this study was to determine whether there is evidence for hepatocellular radiation injury following treatment with (90)Y-SMT487 ((90)Y-DOTA-tyr3-octreotide, OctreoTher(TM)) in patients with extensive liver metastases from neuroendocrine tumors. Patients reported in this study participated in a Phase II trial of efficacy and safety of (90)Y-SMT487. The trial design called for three treatment cycles of 120 mCi each (4400 MBq) of (90)Y-SMT487. (111)In-pentetreotide SPECT images were used to determine the extent of liver metastases. Serum AST, ALT, and alkaline phosphatase levels were obtained at baseline and following each cycle of therapy. Least squares fit was applied to the serial liver enzyme measurements in patients with extensive liver metastases. Post-therapy liver enzyme measurements were also evaluated using WHO common toxicity criteria. Repeated-measures ANOVA and paired t-test were applied to the serial enzyme measures. There were 21 subjects. Fifteen of these had hepatic metastases with 12 demonstrating extensive (defined as 25% or more) liver involvement. In only 4 of these 15 did any of the three enzyme levels increase in WHO toxicity grade from baseline to final follow-up. We conclude that patients with diffuse SSTR positive hepatic metastases can be treated with a cumulative administered activity of 360 mCi (90)Y-SMT487 with only a small chance of developing mild acute or subacute hepatic radiation injury.