U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C17H14BrN3O
Molecular Weight 356.217
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of WP-1066

SMILES

C[C@H](NC(=O)C(=C\C1=NC(Br)=CC=C1)\C#N)C2=CC=CC=C2

InChI

InChIKey=VFUAJMPDXIRPKO-LQELWAHVSA-N
InChI=1S/C17H14BrN3O/c1-12(13-6-3-2-4-7-13)20-17(22)14(11-19)10-15-8-5-9-16(18)21-15/h2-10,12H,1H3,(H,20,22)/b14-10+/t12-/m0/s1

HIDE SMILES / InChI

Molecular Formula C17H14BrN3O
Molecular Weight 356.217
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

Description

WP1066 is a cell-permeable AG490 tyrphostin analog that effectively inhibits the phosphorylation of Janus kinase 2 (JAK2) and its downstream signal transducer and activator of transcription 3 (STAT3) in a dose- and time-dependent manner. As a result, WP1066 concentrations in the low micromolar range induced time- and dose-dependent antiproliferative and proapoptotic effects in cancer cells. WP1066 has been used in Phase I trial studying the treatment of melanoma, brain cancer, solid tumors, and central nervous system neoplasms.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
2.3 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
1.5 μg/mL
200 mg/kg single, oral
WP 1066 plasma
Mus musculus

T1/2

ValueDoseCo-administeredAnalytePopulation
3 h
200 mg/kg single, oral
WP 1066 plasma
Mus musculus

PubMed

Sample Use Guides

In Vivo Use Guide
6 mg/kg 2 times per day on Monday, Wednesday, and Friday of Weeks 1 and 2 of each 28-day cycle.
Route of Administration: Oral
In Vitro Use Guide
WP1066 was identified as a ceramide glucosyltransferase inhibitor by a screen of known small molecule inhibitors of various enzymes and protein factors. WP1066 inhibited the activity of ceramide glucosyltransferase with an IC50 of 7.2 uM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6-NBD-ceramide and UDP-glucose.
Substance Class Chemical
Record UNII
63V8AIE65T
Record Status Validated (UNII)
Record Version