C-16

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H8N4OS
Molecular Weight	268.294
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1NC2=CC=C3N=CSC3=C2\C1=C\C4=CN=CN4

InChI

InChIKey=VFBGXTUGODTSPK-BAQGIRSFSA-N

InChI=1S/C13H8N4OS/c18-13-8(3-7-4-14-5-15-7)11-9(17-13)1-2-10-12(11)19-6-16-10/h1-6H,(H,14,15)(H,17,18)/b8-3-

HIDE SMILES / InChI

Molecular Formula	C13H8N4OS
Molecular Weight	268.294
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12890478
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19046382 | https://www.ncbi.nlm.nih.gov/pubmed/26400930 | https://www.ncbi.nlm.nih.gov/pubmed/22076029

C16 (PKRi) is a selective inhibitor of the enzyme double-stranded RNA-dependent protein kinase (PKR). PKRi prevents striatal neurodegeneration and improves behavioral outcomes in a chemically induced mouse model of Huntington's disease, the efffect mediated by off-target inhibition of CDKs. PKRi restored memory deficit in a mouse model of Alzheimer's disease. In a mouse model of colon-26 adenocarcinoma, treatment with C16 lead to a significantly higher level of blood glucose and lower level of serum triglyceride compared with placebo group, which indicates potential use for alleviation of cachexia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Interferon-induced, double-stranded RNA-activated protein kinase 2 Target ID: P19525 Gene ID: 5610.0 Gene Symbol: EIF2AK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12890478	Inhibitor 8504	0.21 µM [IC50]
Cyclin-dependent kinase 2 23 Target ID: P24941 Gene ID: 1017.0 Gene Symbol: CDK2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19046382	Inhibitor 8504
Cyclin-dependent kinase 5 9 Target ID: CHEMBL4036 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19046382	Inhibitor 8504
Glycogen synthase kinase-3 alpha 6 Target ID: P49840 Gene ID: 2931.0 Gene Symbol: GSK3A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19046382	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Huntington's disease 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19046382	Primary	Preclinical	Unknown Approved Use Unknown
Cachexia 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22076029	Palliative	Preclinical	Unknown Approved Use Unknown
Sporadic Alzheimer's disease 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26400930	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
PKR Inhibition Rescues Memory Deficit and ATF4 Overexpression in ApoE ε4 Human Replacement Mice.	2015-09-23	26400930
Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate.	2012-02	22076029
A chemical compound commonly used to inhibit PKR, {8-(imidazol-4-ylmethylene)-6H-azolidino[5,4-g] benzothiazol-7-one}, protects neurons by inhibiting cyclin-dependent kinase.	2008-11	19046382
Small molecule inhibitors of the RNA-dependent protein kinase.	2003-08-15	12890478

Patents

Sample Use Guides

In Vivo Use Guide

In the model of Huntington's disease, C16 was administered to mice intraperioneally at the dose of 0.27 mg/kg once a day for 5 days.

Route of Administration: Intraperitoneal

In Vitro Use Guide

Kinase inhibition was measured using rate of a transfer of [gamma32P]Atp to poly[I:C] after incubation with 68 nM PKR in 20 mM Tris-HCl buffer (pH 7.6). IC50 for compound 16 was 0.21 uM.

Substance Class	Chemical Created by `admin` on `Tue Apr 01 19:01:25 GMT 2025` Edited by `admin` on `Tue Apr 01 19:01:25 GMT 2025`
Record UNII	C9Q75QZK84
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

C-16

Code

English

GW-506033X

Preferred Name

English

C16

Code

English

IMIDAZOLO-OXINDOLE PKR INHIBITOR C16

Common Name

English

C16 (PKR INHIBITOR)

Code

English

7H-PYRROLO(2,3-G)BENZOTHIAZOL-7-ONE, 6,8-DIHYDRO-8-(1H-IMIDAZOL-5-YLMETHYLENE)-

Systematic Name

English

6,8-DIHYDRO-8-(1H-IMIDAZOL-5-YLMETHYLENE)-7H-PYRROLO(2,3-G)BENZOTHIAZOL-7-ONE

Systematic Name

English

7H-PYRROLO(2,3-G)BENZOTHIAZOL-7-ONE, 6,8-DIHYDRO-8-(1H-IMIDAZOL-5-YLMETHYLENE)-, (8Z)-

Systematic Name

English

(8Z)-8-(1H-IMIDAZOL-5-YLMETHYLIDENE)-6H,7H,8H-(1,3)THIAZOLO(5,4-E)INDOL-7-ONE

Systematic Name

English

Code System Code Type Description

WIKIPEDIA

C16_(drug)