LADUVIGLUSIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H18Cl2N8
Molecular Weight	465.338
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CNC(=N1)C2=CN=C(NCCNC3=NC=C(C=C3)C#N)N=C2C4=CC=C(Cl)C=C4Cl

InChI

InChIKey=AQGNHMOJWBZFQQ-UHFFFAOYSA-N

InChI=1S/C22H18Cl2N8/c1-13-10-29-21(31-13)17-12-30-22(32-20(17)16-4-3-15(23)8-18(16)24)27-7-6-26-19-5-2-14(9-25)11-28-19/h2-5,8,10-12H,6-7H2,1H3,(H,26,28)(H,29,31)(H,27,30,32)

HIDE SMILES / InChI

Molecular Formula	C22H18Cl2N8
Molecular Weight	465.338
Charge	0
Count

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

Description
Sources: http://adisinsight.springer.com/drugs/800015112
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12606497

CHIR 99021 is a selective, pyridimidine-based, glycogen synthase kinase 3 inhibitor that is effective at low nanomolar concentrations in enzyme assays and submicromolar concentrations in isolated cells and tissues. Chiron was developing CHIR 99021 for potential use in the treatment of type 2 diabetes mellitus. CHIR 99021 promoted insulin-mediated glucose uptake and increased glucose disposal in rodent models of diabetes. However, there has been no recent development reported.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glycogen synthase kinase-3 alpha 5 Target ID: CHEMBL2850 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12606497	Inhibitor 8297		10.0 nM [IC50]
Glycogen synthase kinase-3 beta 51 Target ID: CHEMBL262 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12606497	Inhibitor 8297		6.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: http://adisinsight.springer.com/drugs/800015112 https://www.ncbi.nlm.nih.gov/pubmed/12606497	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
		252160102
Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity.	1993 Aug 15	8356085
Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice.	1999 Aug	10426388
Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.	2000 Feb	10868943
Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo.	2003 Mar	12606497
Coordinated waves of gene expression during neuronal differentiation of embryonic stem cells as basis for novel approaches to developmental neurotoxicity testing.	2011 Mar	20865013
Glycogen synthase kinase-3β is required for the induction of skeletal muscle atrophy.	2011 Nov	21832246
Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer's disease.	2012 May 23	22623685
Roles of glycogen synthase kinase 3 in Alzheimer's disease.	2012 Sep	22272620
Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation.	2015 May 29	25897075
Analysis of Glycogen Synthase Kinase Inhibitors That Regulate Cytochrome P450 Expression in Primary Human Hepatocytes by Activation of β-Catenin, Aryl Hydrocarbon Receptor and Pregnane X Receptor Signaling.	2015 Nov	26259606

Patents

Sample Use Guides

In Vivo Use Guide

In ZDF rats, a single oral dose 30 mg/kg of CHIR 99021 rapidly lowered plasma glucose.

Route of Administration: Oral

In Vitro Use Guide

rostral (r2–3) hindbrain hindbrain neural stem cells are efficiently specified by 1.4 µM CHIR99021

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:11:20 GMT 2023` Edited by `admin` on `Sat Dec 16 09:11:20 GMT 2023`
Record UNII	234CMT4GK4
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LADUVIGLUSIB

Official Name

English

CT99021

Code

English

CHIR-99021

Code

English

laduviglusib [INN]

Common Name

English

3-PYRIDINECARBONITRILE, 6-((2-((4-(2,4-DICHLOROPHENYL)-5-(5-METHYL-1H-IMIDAZOL-2-YL)-2-PYRIMIDINYL)AMINO)ETHYL)AMINO)-

Systematic Name

English

CT-99021

Code

English

6-((2-((4-(2,4-DICHLOROPHENYL)-5-(4-METHYL-1H-IMIDAZOL-2-YL)PYRIMIDIN-2-YL)AMINO)ETHYL)AMINO)NICOTINONITRILE

Systematic Name

English

CHR00921

Code

English

LADUVIGLUSIB [USAN]

Common Name

English

FX03

Code

English

CHR-00921

Code

English

CHIR-911

Code

English

Code System Code Type Description

USAN

JK-160