GSK2245035   Click here for help

GtoPdb Ligand ID: 9254

Synonyms: compound 32 [PMID: 26861551]
Immunopharmacology Ligand
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.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 102.06
Molecular weight 390.27
XLogP 3.19
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCCC(Oc1nc(N)c2c(n1)n(CCCCCN1CCCCC1)c(=O)[nH]2)C
Isomeric SMILES CCC[C@@H](Oc1nc(N)c2c(n1)n(CCCCCN1CCCCC1)c(=O)[nH]2)C
InChI InChI=1S/C20H34N6O2/c1-3-10-15(2)28-19-23-17(21)16-18(24-19)26(20(27)22-16)14-9-5-8-13-25-11-6-4-7-12-25/h15H,3-14H2,1-2H3,(H,22,27)(H2,21,23,24)/t15-/m0/s1
InChI Key LFMPVTVPXHNXOT-HNNXBMFYSA-N
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]