Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H15N3O3 |
Molecular Weight | 297.3086 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=NC=NC(NC3=CC=C(O)C=C3)=C2C=C1OC
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)
Molecular Formula | C16H15N3O3 |
Molecular Weight | 297.3086 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/19414010 | https://www.ncbi.nlm.nih.gov/pubmed/10389946Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17631002
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19414010 | https://www.ncbi.nlm.nih.gov/pubmed/10389946
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).
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2148 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10389946 |
78.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Preventing | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents. | 1999 Jun |
|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17631002 https://www.ncbi.nlm.nih.gov/pubmed/10537365
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10389946
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
Edited
Sat Dec 16 14:30:54 GMT 2023
by
admin
on
Sat Dec 16 14:30:54 GMT 2023
|
Record UNII |
1J8Q49TR3I
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Code | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DTXSID301226692
Created by
admin on Sat Dec 16 14:30:54 GMT 2023 , Edited by admin on Sat Dec 16 14:30:54 GMT 2023
|
PRIMARY | |||
|
CHEMBL405130
Created by
admin on Sat Dec 16 14:30:54 GMT 2023 , Edited by admin on Sat Dec 16 14:30:54 GMT 2023
|
PRIMARY | |||
|
202475-60-3
Created by
admin on Sat Dec 16 14:30:54 GMT 2023 , Edited by admin on Sat Dec 16 14:30:54 GMT 2023
|
PRIMARY | |||
|
3794
Created by
admin on Sat Dec 16 14:30:54 GMT 2023 , Edited by admin on Sat Dec 16 14:30:54 GMT 2023
|
PRIMARY | |||
|
1J8Q49TR3I
Created by
admin on Sat Dec 16 14:30:54 GMT 2023 , Edited by admin on Sat Dec 16 14:30:54 GMT 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLIC ENZYME -> SUBSTRATE | |||
|
METABOLIC ENZYME -> SUBSTRATE |
|
||
|
TARGET -> INHIBITOR |
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLITE -> PARENT | |||
|
METABOLITE -> PARENT |