ST1535
目录号 : GC48102
An adenosine A2A receptor antagonist
Cas No.:496955-42-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ST1535 is an adenosine A2A receptor antagonist.1 It is selective for adenosine A2A over A1 receptors (Kis = 2.3 and 107 nM, respectively, in radioligand binding assays). ST1535 inhibits agonist-induced production of cAMP in CHO cells expressing adenosine A2A receptors (IC50 = 353 nM). In vivo, ST1535 (10 and 20 mg/kg) reduces haloperidol-induced catalepsy in mice. It reduces the number of jaw tremors in a rat model of Parkinsonian jaw tremors induced by tacrine .2 ST1535 (20 and 40 mg/kg) increases locomotor activity and reverses motor disabilities in a marmoset model of MPTP-induced Parkinson's disease.3
1.Stasi, M.A., Borsini, F., Varani, K., et al.ST 1535: a preferential A2A adenosine receptor antagonistInt. J. Neuropsychopharmacol.9(5)575-584(2006) 2.Tronci, E., Simola, N., Borsini, F., et al.Characterization of the antiparkinsonian effects of the new adenosine A2A receptor antagonist ST1535: acute and subchronic studies in ratsEur. J. Pharmacol.566(1-3)94-102(2007) 3.Rose, S., Jackson, M.J., Smith, L.A., et al.The novel adenosine A2a receptor antagonist ST1535 potentiates the effects of a threshold dose of L-DOPA in MPTP treated common marmosetsEur. J. Pharmacol.546(1-3)82-87(2006)
| Cas No. | 496955-42-1 | SDF | |
| Canonical SMILES | CCCCC1=NC(N)=C2C(N(C)C(N3N=CC=N3)=N2)=N1 | ||
| 分子式 | C12H16N8 | 分子量 | 272.3 |
| 溶解度 | DMF: 5mg/mL,DMSO: 5mg/mL,DMSO:PBS (pH 7.2) (1:9): 0.1mg/mL | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6724 mL | 18.3621 mL | 36.7242 mL |
| 5 mM | 0.7345 mL | 3.6724 mL | 7.3448 mL |
| 10 mM | 0.3672 mL | 1.8362 mL | 3.6724 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold dose of l-dopa in unilaterally 6-OHDA-lesioned rats
Brain Res 2007 Feb 16;1133(1):110-4.PMID:17196564DOI:10.1016/j.brainres.2006.10.038.
Adenosine A2a antagonists can modulate dopamine-mediated motor behaviours, however, their ability to induce rotational behaviour in 6-hydroxydopamine (6-OHDA)-lesioned rats and to potentiate the effects of l-dopa differs. We now report on the effects of the novel A2a antagonist ST1535 on rotational responses in this model. When administered alone, ST1535 (2.5-40 mg/kg po) enhanced exploratory behaviour and produced a dose-related increase in ipsilateral rotation in rats with a unilateral 6-OHDA lesion of the nigro-striatal pathway. Administration of ST1535 (40 mg/kg po) in combination with a high dose of l-dopa (12 mg/kg ip) caused marked contraversive rotation but did not alter the rotational response produced by l-dopa alone. In contrast, when administered in combination with l-dopa (7 mg/kg ip) that alone produced a submaximal circling response, ST1535 enhanced the intensity and duration of rotation. These results suggest that ST1535 is able to alter dopamine-mediated behaviour when given alone and to potentiate the effects of submaximal doses of l-dopa. ST1535 may be useful in the treatment of Parkinson's disease and effective in reducing the use of l-dopa.
Animal models of Parkinson׳s disease: Effects of two adenosine A2A receptor antagonists ST4206 and ST3932, metabolites of 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine (ST1535)
Eur J Pharmacol 2015 Aug 15;761:353-61.PMID:25936513DOI:10.1016/j.ejphar.2015.03.070.
Antagonism of the adenosine A2A receptor represents a promising strategy for non-dopaminergic treatment of Parkinson׳s disease (PD). Previously, the adenosine A2A receptor antagonist ST1535 was shown to possess potential beneficial effects in animal models of PD. Two metabolites of ST1535, namely ST3932 and ST4206, were tested in vitro to assess their affinity and activity on cloned human A2A adenosine receptors, and their metabolic profile. Additionally, ST3932 and ST4206 were investigated in vivo in animal models of PD following oral/intraperitoneal administration of 10, 20 and 40mg/kg using ST1535 as a reference compound. ST3932 and ST4206 displayed high affinity and antagonist behaviour for cloned human adenosine A2A receptors. The Ki values for ST1535, ST3932 and ST4206 were 8, 8 and 12nM, respectively, and their IC50 values on cyclic AMP were 427, 450 and 990nM, respectively. ST1535, ST3932 and ST4206 antagonized (orally) haloperidol-induced catalepsy in mice, potentiated (intraperitoneally) the number of contralateral rotations induced by l-3,4-dihydroxyphenylalanine (l-DOPA) (3mg/kg) plus benserazide (6mg/kg) in 6-Hydroxydopamine hydrobromide (6-OHDA)-lesioned rats, and increased mouse motor activity by oral route. Thus, ST3932 and ST4206, two ST1535 metabolites, show a pharmacological activity similar to ST1535, both in vitro and in vivo, and may be regarded as an interesting pharmacological alternative to ST1535.
Neuroprotective and anti-inflammatory effects of the adenosine A(2A) receptor antagonist ST1535 in a MPTP mouse model of Parkinson's disease
Synapse 2011 Mar;65(3):181-8.PMID:20665698DOI:10.1002/syn.20833.
Adenosine A(2A) receptor antagonists are one of the most attractive classes of drug for the treatment of Parkinson's disease (PD) as they are effective in counteracting motor dysfunctions and display neuroprotective and anti-inflammatory effects in animal models of PD. In this study, we evaluated the neuroprotective and anti-inflammatory properties of the adenosine A(2A) receptor antagonist ST1535 in a subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. C57BL/6J mice were repeatedly administered with vehicle, MPTP (20 mg/kg), or MPTP + ST1535 (2 mg/kg). Mice were sacrificed three days after the last administration of MPTP. Immunohistochemistry for tyrosine hydroxylase (TH) and cresyl violet staining were employed to evaluate dopaminergic neuron degeneration in the substantia nigra pars compacta (SNc) and caudate-putamen (CPu). CD11b and glial fibrillary acidic protein (GFAP) immunoreactivity were, respectively, evaluated as markers of microglial and astroglial response in the SNc and CPu. Stereological analysis for TH revealed a 32% loss of dopaminergic neurons in the SNc after repeated MPTP administration, which was completely prevented by ST1535 coadministration. Similarly, CPu decrease in TH (25%) was prevented by ST1535. MPTP treatment induced an intense gliosis in both the SNc and CPu. ST1535 totally prevented CD11b immunoreactivity in both analyzed areas, but only partially blocked GFAP increase in the SNc and CPu. A(2A) receptor antagonism is a new opportunity for improving symptomatic PD treatment. With its neuroprotective effect on dopaminergic neuron toxicity induced by MPTP and its antagonism on glial activation, ST1535 represents a new prospect for a disease-modifying drug.
The novel adenosine A2a receptor antagonist ST1535 potentiates the effects of a threshold dose of L-DOPA in MPTP treated common marmosets
Eur J Pharmacol 2006 Sep 28;546(1-3):82-7.PMID:16925991DOI:10.1016/j.ejphar.2006.07.017.
Adenosine A(2a) receptor antagonists may represent a novel non-dopaminergic approach to the treatment of Parkinson's disease. However, there is little information available on their ability to reverse motor deficits in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP)-treated primates. We have studied the effects of the novel A(2a) receptor antagonist 2-butyl-9-methyl-8-(2H-1,2,3-triazol 2-yl)-9 H-purin-6-ylamine (ST1535) alone and in combination with l-3, 4-dihydroxyphenylalanine (L-DOPA) in MPTP-treated common marmosets. ST1535 (10, 20 and 40 mg/kg, p.o.) when administered alone to MPTP-treated common marmosets produced a dose related increase in locomotor motor activity and tended to reverse motor disability. Treatment with a threshold dose of L-DOPA (2.5 mg/kg, p.o.) produced an increase in locomotor activity and again tended to reverse motor disability. When L-DOPA (2.5 mg/kg, p.o.) was administered in combination with ST1535 (20 mg/kg, p.o.), there was an enhancement in the intensity and duration of the effect of L-DOPA (2.5 mg/kg, p.o.) in reversing motor deficits as shown by both a further increase in locomotor activity and reversal of motor disability. The combination of L-DOPA (2.5 mg/kg, p.o.) plus ST1535 (20 mg/kg, p.o.) significantly increased "on time" in these animals. These data substantiate the evidence that adenosine A(2a) receptor antagonists are able to reverse motor deficits in a highly predictive model of clinical efficacy in Parkinson's disease. The data suggests that ST1535 will be an effective anti-parkinsonian agent in combination with L-DOPA and allow a reduction in l-DOPA usage in the treatment of Parkinson's disease.
Synthesis and biological evaluation of metabolites of 2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine (ST1535), a potent antagonist of the A2A adenosine receptor for the treatment of Parkinson's disease
J Med Chem 2013 Jul 11;56(13):5456-63.PMID:23789814DOI:10.1021/jm400491x.
The synthesis and preliminary in vitro evaluation of five metabolites of the A2A antagonist ST1535 (1) are reported. The metabolites, originating in vivo from enzymatic oxidation of the 2-butyl group of the parent compound, were synthesized from 6-chloro-2-iodo-9-methyl-9H-purine (2) by selective C-C bond formation via halogen/magnesium exchange reaction and/or palladium-catalyzed reactions. The metabolites behaved in vitro as antagonist ligands of cloned human A2A receptor with affinities (Ki 7.5-53 nM) comparable to that of compound 1 (Ki 10.7 nM), thus showing that the long duration of action of 1 could be in part due to its metabolites. General behavior after oral administration in mice was also analyzed.