Synonyms: compound 32 [PMID: 26861551]
Compound class:
Synthetic organic
Comment: GSK2245035 is reported as a selective Toll-like receptor 7 (TLR7) agonist, with potential clinical action as an intranasally administered anti-asthmatic [2]. It is Example 22 claimed in patent WO2010018133 [3].
The TLR7- IFNα pathway is a novel pathway being investigated for pharmacological intervention in allergic asthma. |
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References |
1. Aryan Z, Holgate ST, Radzioch D, Rezaei N. (2014)
A new era of targeting the ancient gatekeepers of the immune system: toll-like agonists in the treatment of allergic rhinitis and asthma. Int Arch Allergy Immunol, 164 (1): 46-63. [PMID:24853609] |
2. Biggadike K, Ahmed M, Ball DI, Coe DM, Dalmas Wilk DA, Edwards CD, Gibbon BH, Hardy CJ, Hermitage SA, Hessey JO et al.. (2016)
Discovery of 6-Amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (GSK2245035), a Highly Potent and Selective Intranasal Toll-Like Receptor 7 Agonist for the Treatment of Asthma. J Med Chem, 59 (5): 1711-26. [PMID:26861551] |
3. Biggadike K, Coe DM, Lewell XQ, Mitchell CJ, Smith SA, Trivedi N. (2010)
Purine derivatives for use in the treatment of allergic, inflammatory and infectious diseases. Patent number: WO2010018133. Assignee: Smithkline Beecham Corporation. Priority date: 11/08/2008. Publication date: 18/02/2010. |
4. Ellis AK, Tsitoura DC, Quint D, Powley W, Lee LA. (2017)
Safety and pharmacodynamics of intranasal GSK2245035, a TLR7 agonist for allergic rhinitis: A randomized trial. Clin Exp Allergy, 47 (9): 1193-1203. [PMID:28681506] |
5. Greiff L, Cervin A, Ahlström-Emanuelsson C, Almqvist G, Andersson M, Dolata J, Eriksson L, Högestätt E, Källén A, Norlén P et al.. (2012)
Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis. Respir Res, 13: 53. [PMID:22726593] |
6. Tsitoura D, Ambery C, Price M, Powley W, Garthside S, Biggadike K, Quint D. (2015)
Early clinical evaluation of the intranasal TLR7 agonist GSK2245035: Use of translational biomarkers to guide dosing and confirm target engagement. Clin Pharmacol Ther, 98 (4): 369-80. [PMID:26044169] |