GSK2245035 free base| CAS#1207629-49-9 | TLR7 agonist

MedKoo Cat#: 522629 | Name: GSK2245035 free base

Featured

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GSK2245035 is a selective Toll-like receptor 7 (TLR7) agonist with preferential Type-1 interferon (IFN)-stimulating properties. GSK2245035 displays extraordinary IFNα inducing potency and IFNα/TNFα selectivity. GSK2245035 shows excellent pharmaceutical properties that allow reliable delivery of doses as low as 1 ng per actuation of an intranasal spray formulation. Intranasal GSK2245035 has an acceptable safety profile at doses that induce local TLR7-mediated immune responses.

Chemical Structure

GSK2245035 free base

CAS#1207629-49-9 (free base)

Theoretical Analysis

MedKoo Cat#: 522629

Name: GSK2245035 free base

CAS#: 1207629-49-9 (free base)

Chemical Formula: C20H34N6O2

Exact Mass: 390.2743

Molecular Weight: 390.53

Elemental Analysis: C, 61.51; H, 8.78; N, 21.52; O, 8.19

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 750.00	2 Weeks
10mg	USD 1,250.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1207629-49-9 (free base) 1325212-97-2 (maleate)

Synonym

GSK2245035; GSK-2245035; GSK 2245035; NSC853260; NSC 853260; NSC-853260

IUPAC/Chemical Name

(S)-6-amino-2-(pentan-2-yloxy)-9-(5-(piperidin-1-yl)pentyl)-7,9-dihydro-8H-purin-8-one

InChi Key

LFMPVTVPXHNXOT-HNNXBMFYSA-N

InChi Code

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

SMILES Code

O=C1NC2=C(N)N=C(O[C@@H](C)CCC)N=C2N1CCCCCN3CCCCC3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GSK2245035 is a highly potent and selective intranasal Toll-Like receptor 7 (TLR7) agonist with preferential Type-1 interferon (IFN)-stimulating properties.

In vitro activity:

Further potency enhancement was achieved with the novel (S)-pentyloxy substitution at C-2 leading to the selection of GSK2245035 (32) as an intranasal development candidate. In human cell cultures, compound 32 resulted in suppression of Th2 cytokine responses to allergens, while in vivo intranasal administration at very low doses led to local upregulation of TLR7-mediated cytokines (IP-10). Reference: J Med Chem. 2016 Mar 10;59(5):1711-26. https://pubmed.ncbi.nlm.nih.gov/26861551/

In vivo activity:

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	25.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 390.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Biggadike K, Ahmed M, Ball DI, Coe DM, Dalmas Wilk DA, Edwards CD, Gibbon BH, Hardy CJ, Hermitage SA, Hessey JO, Hillegas AE, Hughes SC, Lazarides L, Lewell XQ, Lucas A, Mallett DN, Price MA, Priest FM, Quint DJ, Shah P, Sitaram A, Smith SA, Stocker R, Trivedi NA, Tsitoura DC, Weller V. 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. 2016 Mar 10;59(5):1711-26. doi: 10.1021/acs.jmedchem.5b01647. Epub 2016 Feb 10. PMID: 26861551.

In vitro protocol:

In vivo protocol:

1: Posobiec LM, Hillegas AE, Baker A, Phadnis-Moghe AS, Maier CC, Stanislaus DJ, Bray M, Price MA. GSK2245035, a TLR7 agonist, Does Not Increase Pregnancy Loss in Cynomolgus Monkeys. J Reprod Immunol. 2021 Feb;143:103242. doi: 10.1016/j.jri.2020.103242. Epub 2020 Nov 2. PMID: 33212303. 2: Siddall H, Quint D, Pandya H, Powley W, Shabbir S, Hohlfeld JM, Singh D, Lee L. Intranasal GSK2245035, a Toll-like receptor 7 agonist, does not attenuate the allergen-induced asthmatic response in a randomized, double-blind, placebo- controlled experimental medicine study. PLoS One. 2020 Nov 9;15(11):e0240964. doi: 10.1371/journal.pone.0240964. PMID: 33166307; PMCID: PMC7652256. 3: Ellis AK, Tsitoura DC, Quint D, Powley W, Lee LA. Safety and pharmacodynamics of intranasal GSK2245035, a TLR7 agonist for allergic rhinitis: A randomized trial. Clin Exp Allergy. 2017 Sep;47(9):1193-1203. doi: 10.1111/cea.12974. Epub 2017 Aug 11. PMID: 28681506. 4: Biggadike K, Ahmed M, Ball DI, Coe DM, Dalmas Wilk DA, Edwards CD, Gibbon BH, Hardy CJ, Hermitage SA, Hessey JO, Hillegas AE, Hughes SC, Lazarides L, Lewell XQ, Lucas A, Mallett DN, Price MA, Priest FM, Quint DJ, Shah P, Sitaram A, Smith SA, Stocker R, Trivedi NA, Tsitoura DC, Weller V. 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. 2016 Mar 10;59(5):1711-26. doi: 10.1021/acs.jmedchem.5b01647. Epub 2016 Feb 10. PMID: 26861551. 5: Tsitoura D, Ambery C, Price M, Powley W, Garthside S, Biggadike K, Quint D. Early clinical evaluation of the intranasal TLR7 agonist GSK2245035: Use of translational biomarkers to guide dosing and confirm target engagement. Clin Pharmacol Ther. 2015 Oct;98(4):369-80. doi: 10.1002/cpt.157. PMID: 26044169.