Synonyms: WP 1066 | WP-1066
Compound class:
Synthetic organic
Comment: WP1066 is a novel inhibitor of STAT3 and JAK2 [7]. It is orally bioavailable, and has demonstrated antineoplastic and immunomodulatory activities in vitro and in vivo [1-3,6]. WP1066 has also been reported as a channel blocker at the KV1.3 voltage-gated potassium channel (KCNA3) that preferentially interacts with open channels [5].
An analogue of WP1066, WP1220 (structure undisclosed, Nov. 2022), is another clinical lead STAT3 inhibitor. WP1220 is in development for topical application as a therapy for the dermatological condition mycosis fungoides, the most common type of cutaneous T-cell lymphoma (CTCL). Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
|
References |
1. Allaf A, Victoria B, Rosario R, Misztal C, Humayun Gultekin S, Dinh CT, Fernandez-Valle C. (2022)
WP1066 induces cell death in a schwannomatosis patient-derived schwannoma cell line. Cold Spring Harb Mol Case Stud, 8 (4). [PMID:35732500] |
2. Bill MA, Fuchs JR, Li C, Yui J, Bakan C, Benson Jr DM, Schwartz EB, Abdelhamid D, Lin J, Hoyt DG et al.. (2010)
The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity. Mol Cancer, 9: 165. [PMID:20576164] |
3. Ferrajoli A, Faderl S, Van Q, Koch P, Harris D, Liu Z, Hazan-Halevy I, Wang Y, Kantarjian HM, Priebe W et al.. (2007)
WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res, 67 (23): 11291-9. [PMID:18056455] |
4. Lü Z, Li X, Li K, Wang C, Du T, Huang W, Ji M, Li C, Xu F, Xu P et al.. (2021)
Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors. ACS Med Chem Lett, 12 (5): 696-703. [PMID:34055214] |
5. Li M, Yu H. (2021)
Identification of WP1066, an inhibitor of JAK2 and STAT3, as a KV 1.3 potassium channel blocker. Br J Pharmacol, 178 (13): 2617-2631. [PMID:33689167] |
6. Tsujita Y, Horiguchi A, Tasaki S, Isono M, Asano T, Ito K, Asano T, Mayumi Y, Kushibiki T. (2017)
STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells. Oncol Rep, 38 (4): 2197-2204. [PMID:28849140] |
7. Verstovsek S, Manshouri T, Quintás-Cardama A, Harris D, Cortes J, Giles FJ, Kantarjian H, Priebe W, Estrov Z. (2008)
WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation. Clin Cancer Res, 14 (3): 788-96. [PMID:18245540] |