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Details

Stereochemistry ACHIRAL
Molecular Formula C16H15N3O3
Molecular Weight 297.3092
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of JANEX-1

SMILES

COc1cc2c(cc1OC)ncnc2Nc3ccc(cc3)O

InChI

InChIKey=HOZUXBLMYUPGPZ-UHFFFAOYSA-N
InChI=1S/C16H15N3O3/c1-21-14-7-12-13(8-15(14)22-2)17-9-18-16(12)19-10-3-5-11(20)6-4-10/h3-9,20H,1-2H3,(H,17,18,19)

HIDE SMILES / InChI

Molecular Formula C16H15N3O3
Molecular Weight 297.3092
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17631002

JANEX-1 (WHI-P131), a selective Janus kinase 3 (JAK3) inhibitor, has been shown to delay the onset of diabetes in the NOD mouse model. It is a cell-permeable, reversible, potent, ATP-competitive, and specific inhibitor of JAK3 (IC50 = 78 uM); has no effect on JAK1, JAK2, or Zap/Syk or SRC tyrosine kinases. JANEX-1 has a potent inhibitory effect on cytokine-induced β-cell damage. JANEX-1 has a therapeutic potential in the treatment and prevention of type 1 diabetes. JANEX-1 induced apoptosis in JAK3-expressing human leukemia cell lines NALM-6 and LC1. JANEX-1 inhibited the clonogenic growth of JAK3-positive leukemia cell lines DAUDI, RAMOS, LC1;19, NALM-6, MOLT-3, and HL-60 (but not JAK3-negative BT-20 breast cancer, M24-MET melanoma, or SQ20B squamous carcinoma cell lines) in a concentration-dependent fashion. Potent and specific inhibitors of JAK3 such as JANEX-1 may provide the basis for the design of new treatment strategies against acute lymphoblastic leukemia, the most common form of childhood cancer. JANEX-1/WHI-P131 also showed potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile. JANEX-1 may prove useful to prevent or alleviate the symptoms of endometriosis (EMS).

Approval Year

PubMed

PubMed

TitleDatePubMed
Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents.
1999 Jun
Recent advances in JAK3 kinase inhibitors.
1999 Oct
Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1.
2007 Aug
The specificity of JAK3 kinase inhibitors.
2008 Feb 15
JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway.
2009 Jul 15
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: The pharmacokinetics and toxicity of JANEX-1 has been evaluated in mice, rats, and monkeys. Following i.v. administration, the terminal elimination half-life (t1 ⁄ 2) of JANEX-1 was 103 min in mice, 73 min in rats, and 45 min in monkeys. Intravenously administered JANEX-1 showed a very wide tissue distribution. Intraperitoneally administered JANEX-1 was rapidly absorbed in both mice and rats. JANEX- 1 was quickly absorbed after oral administration in mice with a tmax of 6 min, but its oral bioavailability was relatively low (30%). Topical administration of JANEX-1 (1.0 mg/cm2) over the UVB target skin area on the dorsal surface 15 min before each UVB exposure significantly suppressed the photocarcinogenesis of mice.https://www.ncbi.nlm.nih.gov/pubmed/20486473
Mice: In the mouse model of airway inflammation, JANEX-1 treatment (20 mg ⁄ kg or 40 mg ⁄ kg) of ovalbumin (OVA)-sensitized BALB⁄ c mice via oral gavage significantly reduced the magnitude of the inflammatory response to aerosolized OVA challenge. In the mouse model of irritable bowel disease (IBD), treatment of BALB⁄ c mice with 25 mg ⁄ kg JANEX-1 (i.p.) prevented 2,4,6,-trinitrobenzene sulfonic acid (TNBS)-induced IBD.
Route of Administration: Other
Treatment of NALM-6 leukemia cells with JANEX-1 (WHI-P131) at 7.4 ug/ml (25 uM) to 60 ug/ml (200 uM) for 24 or 48 h increased the number of depolarized mitochondria in a concentration- and time-dependent manner as determined by flow cytometry using DiIC1
Substance Class Chemical
Created
by admin
on Sat Jun 26 11:44:45 UTC 2021
Edited
by admin
on Sat Jun 26 11:44:45 UTC 2021
Record UNII
1J8Q49TR3I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
JANEX-1
Code English
PHENOL, 4-((6,7-DIMETHOXY-4-QUINAZOLINYL)AMINO)-
Systematic Name English
JANEX 1 [WHO-DD]
Common Name English
WHI-P131
Code English
Code System Code Type Description
ChEMBL
CHEMBL405130
Created by admin on Sat Jun 26 11:44:46 UTC 2021 , Edited by admin on Sat Jun 26 11:44:46 UTC 2021
PRIMARY
CAS
202475-60-3
Created by admin on Sat Jun 26 11:44:46 UTC 2021 , Edited by admin on Sat Jun 26 11:44:46 UTC 2021
PRIMARY
PUBCHEM
3794
Created by admin on Sat Jun 26 11:44:46 UTC 2021 , Edited by admin on Sat Jun 26 11:44:46 UTC 2021
PRIMARY
FDA UNII
1J8Q49TR3I
Created by admin on Sat Jun 26 11:44:46 UTC 2021 , Edited by admin on Sat Jun 26 11:44:46 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
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METABOLITE -> PARENT
METABOLITE -> PARENT