| 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
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
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
Sourcing
PubMed
Patents
Sample Use Guides
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
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.
ACTIVE MOIETY
