EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1



Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1



American Journal of Reproductive Immunology 58(2): 75-97



Endometriosis (EMS) is a chronic inflammatory disease of multifactorial etiology characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity. EMS is a significant public health issue as it affects 15-20% of women in their reproductive age. Clinical symptoms may include pelvic pain, dysmenorrhea, dyspareunia, pelvic/abdominal masses, and infertility. Symptomatic treatments such as surgical resection and/or hormonal suppression of ovarian function and analgesics are not as effective as desired. Consequently, there is an enormous unmet need to develop effective medical therapy capable of preventing the occurrence and recurrence of EMS without undesirable side-effects. EMS-associated intra-abdominal bleeding episodes, local inflammation, adhesions, and i.p. immunologic dysfunction leads to pelvic nociception and pelvic pain. Increasing evidence supports the involvement of allergic-type inflammation in EMS. Invasion of mast cells, degranulation, and proliferation of interstitial component are observed in endometriotic lesions. Presence of activated and degranulating mast cells within the nerve structures can contribute to the development of pain and hyperalgesia by direct effects on primary nociceptive neurons. Therefore, treatments targeting endometrial mast cells may prove effective in preventing or alleviating EMS-associated symptoms. The Janus kinase 3 (JAK3) is abundantly expressed in mast cells and is required for the full expression of high-affinity IgE receptor-mediated mast cell inflammatory sequelae. JANEX-1/WHI-P131 is a rationally designed novel JAK3 inhibitor with 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. We hypothesize that JAK3 inhibitors, especially JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.

(PDF emailed within 0-6 h: $19.90)

Accession: 017244119

Download citation: RISBibTeXText

PMID: 17631002

DOI: 10.1111/j.1600-0897.2007.00502.x



Related references

Targeting Janus kinase 3 with JANEX-1 for prevention of autoimmune type 1 diabetes in NOD mice. Diabetes 52(Supplement 1): A274-A275, 2003

Prevention of islet allograft rejection in diabetic mice by targeting Janus Kinase 3 with 4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (JANEX-1). Arzneimittel-Forschung 53(9): 648-654, 2003

Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL-positive cells. Journal of Hematology & Oncology 7(): 37-37, 2014

Targeting Janus kinase 3 in mast cells prevents immediate hypersensitivity reactions and anaphylaxis. Journal of Biological Chemistry 274(38): 27028-27038, 1999

Treatment of allergic asthma by targeting Janus kinase 3-dependent leukotriene synthesis in mast cells with 4- amino-6,7-dimethoxyquinazoline. Journal of Pharmacology & Experimental Therapeutics 295(3): 912-926, December, 2000

Treatment of allergic asthma by targeting janus kinase 3-dependent leukotriene synthesis in mast cells with 4-(3', 5'-dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97). Journal of Pharmacology and Experimental Therapeutics 295(3): 912-926, 2000

Janus kinase 3 inhibitor WHI-P131/JANEX-1 prevents graft-versus-host disease but spares the graft-versus-leukemia function of the bone marrow allografts in a murine bone marrow transplantation model. Blood 99(11): 4192-4199, 2002

Identification of a potent Janus kinase 3 inhibitor with high selectivity within the Janus kinase family. Journal of Medicinal Chemistry 54(1): 284-288, 2011

The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood 107(1): 176-183, 2005

Chemoprevention of colorectal cancer by targeting Janus kinase 3 with a rationally designed small molecule inhibitor. Nutrition and Cancer 62(7): 968-972, 2011

Ruxolitinib: an oral Janus kinase 1 and Janus kinase 2 inhibitor in the management of myelofibrosis. Postgraduate Medicine 125(1): 128-135, 2013

Targeting the Janus-activated kinase-2-STAT3 signalling pathway in pancreatic cancer using the HSP90 inhibitor ganetespib. European Journal of Cancer 52(): 109-119, 2016

Targeting mast cells: a new way to treat endometriosis. Expert Opinion on Therapeutic Targets 21(1): 67-75, 2016

Janus reveals another face: the biologic rationale for targeting Janus kinase 2 in lymphoma. Journal of Clinical Oncology 30(33): 4168-4170, 2013