AKN-028

WARNING: This product is for research use only, not for human or veterinary use.

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.

Price and Availability

AKN-028,is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 205942Name: AKN-028CAS#: 1175017-90-9Chemical Formula: C17H14N6Exact Mass: 302.12799Molecular Weight: 302.33Elemental 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

Technical Data

Additional Information

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.)   

References

1: Eriksson A, Hermanson M, Wickström M, Lindhagen E,Ekholm C, Jenmalm Jensen A, Löthgren A, Lehmann F, Larsson R, Parrow V,Höglund M. The novel tyrosine kinase  inhibitor AKN-028 hassignificant antileukemic activity in cell lines and primary cultures ofacute myeloid leukemia. Blood Cancer J. 2012 Aug 3;2:e81. doi:10.1038/bcj.2012.28. PubMed PMID: 22864397; PubMed Central PMCID:PMC3432483.