WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205942
Description: AKN-028, the FLT3/KIT kinase inhibitor, is an orally bioavailable protein tyrosine kinase inhibitor for FMS-related tyrosine kinase 3 (FLT3; STK1) and stem cell factor receptor (SCFR; KIT), with potential antineoplastic activity. FLT3/KIT kinase inhibitor AKN-028 binds to and inhibits both the wild-type and mutated forms of FLT3 and SCFR. This may result in an inhibition of tumor cell proliferation in cancer cell types that overexpress these receptor tyrosine kinases. Check for active clinical trials or closed clinical trials using this agent.
MedKoo Cat#: 205942
Chemical Formula: C17H14N6
Exact Mass: 302.12799
Molecular Weight: 302.33
Elemental Analysis: C, 67.54; H, 4.67; N, 27.80
Synonym: AKN-028; AKN 028; AKN028
IUPAC/Chemical Name: N2-(1H-indol-5-yl)-6-(pyridin-4-yl)pyrazine-2,3-diamine
InChi Key: JLRIJKVMMZEKDF-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H14N6/c18-16-17(22-13-1-2-14-12(9-13)5-8-20-14)23-15(10-21-16)11-3-6-19-7-4-11/h1-10,20H,(H2,18,21)(H,22,23)
SMILES Code: NC1=NC=C(C2=CC=NC=C2)N=C1NC3=CC4=C(NC=C4)C=C3
AKN-028, a novel tyrosine kinase inhibitor (TKI), is a potent FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor (IC(50)=6 nM), causing dose-dependent inhibition of FLT3 autophosphorylation. Inhibition of KIT autophosphorylation was shown in a human megakaryoblastic leukemia cell line overexpressing KIT. In a panel of 17 cell lines, AKN-028 showed cytotoxic activity in all five AML cell lines included. AKN-028 triggered apoptosis in MV4-11 by activation of caspase 3. In primary AML samples (n=15), AKN-028 induced a clear dose-dependent cytotoxic response (mean IC(50) 1 μM). However, no correlation between antileukemic activity and FLT3 mutation status, or to the quantitative expression of FLT3, was observed. Combination studies showed synergistic activity when cytarabine or daunorubicin was added simultaneously or 24 h before AKN-028. In mice, AKN-028 demonstrated high oral bioavailability and antileukemic effect in primary AML and MV4-11 cells, with no major toxicity observed in the experiment. (source: Blood Cancer J. 2012 Aug 3;2:e81. doi: 10.1038/bcj.2012.28.)
1: Eriksson A, Hermanson M, WickstrÃ¶m M, Lindhagen E, Ekholm C, Jenmalm Jensen A, LÃ¶thgren A, Lehmann F, Larsson R, Parrow V, HÃ¶glund M. The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia. Blood Cancer J. 2012 Aug 3;2:e81. doi: 10.1038/bcj.2012.28. PubMed PMID: 22864397; PubMed Central PMCID: PMC3432483.