AKN-028

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H14N6
Molecular Weight	302.3333
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC=C(N=C1NC2=CC3=C(NC=C3)C=C2)C4=CC=NC=C4

InChI

InChIKey=JLRIJKVMMZEKDF-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C17H14N6
Molecular Weight	302.3333
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/flt3-kit-kinase-inhibitor-akn-028 | https://www.ncbi.nlm.nih.gov/pubmed/22864397 | https://www.ncbi.nlm.nih.gov/pubmed/24200998

AKN-028 is an orally bioavailable protein tyrosine kinase inhibitor for FMS-related tyrosine kinase 3 (IC(50)=6 nM) 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. Akinion Pharmaceuticals is developing AKN-028 for the treatment of acute myeloid leukaemia. AKN-028 is presently undergoing investigation in a phase I/II study.

Originator

Approval Year

PubMed

Title	Date	PubMed
The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia.	2012 Aug 3	22864397
AKN-028 induces cell cycle arrest, downregulation of Myc associated genes and dose dependent reduction of tyrosine kinase activity in acute myeloid leukemia.	2014 Jan 15	24200998

Patents

Sample Use Guides

In Vivo Use Guide

Acute Myelogenous Leukemia: Part 1 of the study is a sequential dose-escalation evaluation of AKN-028. Part 1 started as an accelerated intra-patient dose escalation design in one patient at a time (the N=1 portion), and has switched to standard 3 + 3 design with inter-cohort dose escalation when AUC of 12 uM*hrs has been reached. Starting dose of AKN-028 was 60 mg twice a day.

Route of Administration: Oral

In Vitro Use Guide

AKN-028 is a potent FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor (IC(50)=6 nM), causing dose-dependent inhibition of FLT3 autophosphorylation. In primary AML samples (n=15), AKN-028 induced a clear dose-dependent cytotoxic response (mean IC(50) 1 uM).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:58:28 GMT 2023` Edited by `admin` on `Sat Dec 16 10:58:28 GMT 2023`
Record UNII	Y66IS3CS0R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AKN-028

Common Name

English

N2-(1H-INDOL-5-YL)-6-(PYRIDIN-4-YL)PYRAZINE-2,3-DIAMINE

Systematic Name

English

2,3-PYRAZINEDIAMINE, N3-1H-INDOL-5-YL-5-(4-PYRIDINYL)-

Systematic Name

English

Code System Code Type Description

ChEMBL

CHEMBL3545281