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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
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

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

Curator's Comment: Known to be CNS penetrant in mouse. Human data not available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.3 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.5 μg/mL
200 mg/kg single, oral
dose: 200 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
WP 1066 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3 h
200 mg/kg single, oral
dose: 200 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
WP 1066 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation.
2008 Feb 1
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:15:10 UTC 2023
Edited
by admin
on Sat Dec 16 01:15:10 UTC 2023
Record UNII
63V8AIE65T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
WP-1066
Code English
WP1066
Code English
WP 1066
Code English
2-PROPENAMIDE, 3-(6-BROMO-2-PYRIDINYL)-2-CYANO-N-((1S)-1-PHENYLETHYL)-, (2E)-
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 671018
Created by admin on Sat Dec 16 01:15:10 UTC 2023 , Edited by admin on Sat Dec 16 01:15:10 UTC 2023
Code System Code Type Description
FDA UNII
63V8AIE65T
Created by admin on Sat Dec 16 01:15:10 UTC 2023 , Edited by admin on Sat Dec 16 01:15:10 UTC 2023
PRIMARY
DRUG BANK
DB12679
Created by admin on Sat Dec 16 01:15:10 UTC 2023 , Edited by admin on Sat Dec 16 01:15:10 UTC 2023
PRIMARY
PUBCHEM
11210478
Created by admin on Sat Dec 16 01:15:10 UTC 2023 , Edited by admin on Sat Dec 16 01:15:10 UTC 2023
PRIMARY
NCI_THESAURUS
C111042
Created by admin on Sat Dec 16 01:15:10 UTC 2023 , Edited by admin on Sat Dec 16 01:15:10 UTC 2023
PRIMARY
EPA CompTox
DTXSID50235007
Created by admin on Sat Dec 16 01:15:10 UTC 2023 , Edited by admin on Sat Dec 16 01:15:10 UTC 2023
PRIMARY
CAS
857064-38-1
Created by admin on Sat Dec 16 01:15:10 UTC 2023 , Edited by admin on Sat Dec 16 01:15:10 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY