Tolbutamide (HLS 831)

製品コード：S2443 純度：99.88%

Tolbutamide (HLS 831) is an inhibitor of potassium channel, used for type II diabetes.

CAS No. 64-77-7

サイズ	価格(税別)	在庫状況
50mg	JPY 22000	国内在庫あり
1g	JPY 100500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

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製品安全説明書

現在のバッチを見る： S244301 DMSO] 54 mg/mL] false] Ethanol] 54 mg/mL] false] Water] Insoluble] false 純度： 99.88%

99.88

Tolbutamide (HLS 831)関連製品

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シグナル伝達経路

Potassium Channelシグナル伝達経路

Potassium Channel阻害剤の選択性比較

生物活性

製品説明

Tolbutamide (HLS 831) is an inhibitor of potassium channel, used for type II diabetes.

Targets

Potassium channel ^[3]

In Vitro
In vitro	Tolbutamide belongs to a class of medications called sulfonylureas. Tolbutamide lowers blood sugar by causing the pancreas to produce insulin (a natural substance that is needed to break down sugar in the body) and helping the body use insulin efficiently. This medication will only help lower blood sugar in people whose bodies produce insulin naturally. Tolbutamide is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may occur if high blood sugar is not treated). Tolbutamide inhibits both the basal and the cyclic AMP-stimulated protein kinase activities and the IC50 of Tolbutamide is 4 mM. Similar Tolbutamide concentrations are required for half maximal inhibition of in vitro lipolysis induced by hormones (norepinephrine and ACTH) or by dibutyryl cyclic AMP plus theophylline. Tolbutamide also inhibits both soluble and membrane-bound protein kinase from canine heart. The Tolbutamide inhibition of adipose tissue cyclic AMP-dependent protein kinase is one possible explanation for the antilipolytic effects of this drug. ^[1] Tolbutamide inhibits C6-glioma cell proliferation by increasing Cx43, which correlates with a reduction in pRb phosphorylation due to the up-regulation of the Cdk inhibitors p21 and p27. ^[2] Cytosolic nucelotides enhance the Tolbutamide sensitivity of the ATP-dependent K+ channel in mouse pancreatic B cells by their combined actions at inhibitory and stimulatory receptors. ^[3] Tolbutamide inhibits glucagon-induced phosphorylation of the bifunctional enzyme protein in a dose-dependent manner. By adding 2 mM Tolbutamide, reduces activity of 6PF-2-K and increased activity of Fru-2,6-P2ase in the presence of 10(-9) M glucagon are partially restored. The present results suggest the possibility that Tolbutamide modulates the activity of hepatic 6PF-2-K/Fru-2,6-P2ase through inhibiting a phosphorylation of the enzyme protein. ^[4]
Kinase Assay	cAMP kinase assay
Kinase Assay	Diced epididymal fat pads from fed Wistar rats (175-225 gm) are obtained after decapitation and incubated at 37 °C for two hours in Krebs-bicarbonate buffer containing 1.27 mM CaCl₂. When added, Tolbutamide is present only during the incubation. After incubation fat pads are rinsed and sonicated in cold Krebs-bicarbonate buffer. The aqueous supematants from centrifugation at 50,000 × g for 30 minutes at 4 °C contained 0.75 to 1.25 mg protein per mL and are assayed for cyclic AMP-stimulated protein kinase activity. The assay is performed in 0.2 mL with these additions, 10 μmoles sodium glycerofiosphate pH 7.0, 2 μmoles sodium fluoride, 0.4 μmoles theophylline, 0.1 μmoles ethylene glyool bis (β-aminoethyl ether)-N, N'-tetraaoetic acid, 3 μmoles magnesium chloride, 0.3 mg mixed histone, 2 nmoles (γ- ³²P) ATP, 1 nmoles cyclic AMP when indicated, and 0.05 ml of supernatant.
細胞実験	細胞株	C6 glioma cells
	濃度	400 μM
	反応時間	24 hours
	実験の流れ	C6 glioma cells are incubated in serum-free DMEM at 37 °C for at least 24 hours before each experiment. Tolbutamide (400 μM) is incubated for 24 hours in serum-free medium. Incubations are performed at 37 °C in an atmosphere of 95% air/5% CO₂ with 90–95% humidity.

In Vivo
In Vivo	450 mg Tolbutamide/kg/day given for 7 days significantly increases the binding of insulin to isolated adipocytes. The binding curves reflect an increase in the number of receptor sites rather than in the affinity. The effect is associated with an enhanced response to insulin of the adipose tissue, since the fat cells obtained from animals treated with Tolbutamide convert significantly more glucose to lipids in the presence of insulin than those obtained from the control group. However, the augmentation of insulin binding sites is observed only at a large tolbutamide dosage, which reduces the pancreatic insulin content, the secretory response of the isolated pancreas, and the serum insulin levels. Smaller doses, sufficient to produce metabolic effects via a stimulation of insulin secretion, do not provide additional insulin binding sites. ^[5]
動物実験	動物モデル	Male albino Wistar rats (200-300 g)
	投与量	450 mg/kg
	投与経路	Tolbutamide is administered orally for 7 days.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05830799	Completed	Drug Interaction	Vicore Pharma AB	March 29 2023	Phase 1
NCT05097716	Completed	Healthy Volunteers	Pfizer	November 2 2021	Phase 1
NCT03291288	Completed	Drug Interaction Potential	Daiichi Sankyo	February 26 2018	Phase 1
NCT02819102	Completed	Hereditary Angioedema	BioCryst Pharmaceuticals	March 2016	Phase 1

参考
[1] Wray HL, et al, Biochem Biophys Res Commun. 1973, 53(1), 291-294. [2] Sanchez-Alvarez R, et al, Glia, 2006, 54(2), 125-134. [3] Schwanstecher C, et al, Mol Pharmacol, 1992, 41(3), 480-486. [4] Avame H, et al, Am J Physiol, 1995, 268(3 Pt 1), 392-396. [5] Joost HG, et al, Biochem Pharmacol, 1982, 31(7), 1227-1231. + 展開

参考

+ 展開

化学情報

分子量	270.35	化学式	C₁₂H₁₈N₂O₃S
CAS No.	64-77-7	SDF	Download Tolbutamide (HLS 831) SDFをダウンロードする
Smiles	CCCCNC(=O)NS(=O)(=O)C1=CC=C(C=C1)C
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 54 mg/mL ( (199.74 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 54 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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