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

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