Acetohexamide
(Synonyms: 醋磺己脲) 目录号 : GC33772
A first generation sulfonylurea
Cas No.:968-81-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Acetohexamide is a first generation sulfonylurea that inhibits sulfonylurea receptor 1 (SUR1) linked to the inwardly rectifying potassium channel (KIR6.2) with Ki values of 22.9 and 14.2 ?M in HEK293 cells transfected with the human receptor and in rat brain, respectively.1 It is metabolized to the hypoglycemic compound L-hydroxyhexamide in vivo.2,3 Formulations containing acetohexamide have previously been used in the treatment of type 2 diabetes.
1.Gopalakrishnan, M., Molinari, E.J., Char-Change, S., et al.Pharmacology of human sulphonylurea receptor SUR1 and inward rectifier K+ channel Kir6.2 combination expressed in HEK-293 cellsBr. J. Pharmacol.129(7)1323-1332(2000) 2.McMahon, R.E., Marshall, F.J., and Culp, H.W.The nature of the metabolites of acetohexamide in the rat and in the humanJ. Pharmacol. Exp. Ther.149(2)272-279(1965) 3.Imamura, Y., Sanai, K., Seri, K., et al.Hypoglycemic effect of S(-)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamideLife Sci.69(16)1947-1955(2001)
| Cas No. | 968-81-0 | SDF | |
| 别名 | 醋磺己脲 | ||
| Canonical SMILES | O=S(C1=CC=C(C(C)=O)C=C1)(NC(NC2CCCCC2)=O)=O | ||
| 分子式 | C15H20N2O4S | 分子量 | 324.4 |
| 溶解度 | DMSO : ≥ 39 mg/mL (120.22 mM) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0826 mL | 15.4131 mL | 30.8261 mL |
| 5 mM | 0.6165 mL | 3.0826 mL | 6.1652 mL |
| 10 mM | 0.3083 mL | 1.5413 mL | 3.0826 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Carbonyl reductase activity for Acetohexamide in human erythrocytes
Drug Metab Dispos 1994 May-Jun;22(3):367-70.PMID:8070312doi
Acetohexamide is an oral antidiabetic agent and is metabolized by the reductive conversion of the acetoxy group to a secondary alcohol metabolite. In vivo, many drugs are metabolized by reductase enzymes; however, the characteristics of the enzymes that reduce carbonyl compounds need to be clarified. We tested whether reductase activity for Acetohexamide can be found in human erythrocytes. Enzyme activity was monitored by formation of hydroxyhexamide using HPLC methods. In human erythrocytes, reductase activity (6.10 +/- 1.20 nmol/min/g hemoglobin) (mean +/- SD) was indeed observed, when 0.5 mM Acetohexamide was used as a substrate. KM values and Vmax at the physiologically important pH 7.4 were 0.70 +/- 0.13 mM and 9.19 +/- 0.88 nmol/min/g hemoglobin, respectively. Separation of protein by gel filtration gave one major peak fraction with reductase activity whose molecular weight was estimated to be 31,000. Known substrates of carbonyl reductase such as menadione, daunorubicin, and ethacrynic acid inhibited the Acetohexamide reduction. The Acetohexamide reductase in erythrocyte showed characteristics of carbonyl reductase. Furthermore, Acetohexamide reductase activity in erythrocyte was approximately 30% activity of that of human liver (0.17 +/- 0.05 nmol/min/mg cytosolic protein). The pattern of inhibitors in human liver was essentially the same as that in erythrocytes. It is plausible that the activity in erythrocytes may predict the activity in the liver. It was concluded that carbonyl reductase in human erythrocyte plays an important role in Acetohexamide metabolism.
Chromatographic analysis of Acetohexamide binding to glycated human serum albumin
J Chromatogr B Analyt Technol Biomed Life Sci 2010 Oct 15;878(28):2775-81.PMID:20829128DOI:10.1016/j.jchromb.2010.08.021.
Acetohexamide is a drug used to treat type II diabetes and is tightly bound to the protein human serum albumin (HSA) in the circulation. It has been proposed that the binding of some drugs with HSA can be affected by the non-enzymatic glycation of this protein. This study used high-performance affinity chromatography to examine the changes in acetohexamide-HSA binding that take place as the glycation of HSA is increased. It was found in frontal analysis experiments that the binding of Acetohexamide to glycated HSA could be described by a two-site model involving both strong and weak affinity interactions. The average association equilibrium constant (K(a)) for the high affinity interactions was in the range of 1.2-2.0×10(5)M(-1) and increased in moving from normal HSA to HSA with glycation levels that might be found in advanced diabetes. It was found through competition studies that Acetohexamide was binding at both Sudlow sites I and II on the glycated HSA. The K(a) for Acetohexamide at Sudlow site I increased by 40% in going from normal HSA to minimally glycated HSA but then decreased back to near-normal values in going to more highly glycated HSA. At Sudlow site II, the K(a) for Acetohexamide first decreased by about 40% and then increased in going from normal HSA to minimally glycated HSA and more highly glycated HSA. This information demonstrates the importance of conducting both frontal analysis and site-specific binding studies in examining the effects of glycation on the interactions of a drug with HSA.
Metabolic reduction of Acetohexamide in rat kidney: sex difference and effect of streptozotocin-induced diabetes
J Pharmacobiodyn 1988 May;11(5):309-13.PMID:2971793DOI:10.1248/bpb1978.11.309.
The Acetohexamide reductase activity in 10000 x g supernatant fluids of kidney homogenates was significantly higher in male than in female rats. Although difference in activity of Acetohexamide reductase in the cytosol between the sexes was not observed, the activity in the microsomes was considerably higher in male than in female rats. These findings indicate that the microsomal enzyme plays an important role in the sex difference of Acetohexamide reduction by 10000 x g supernatant fluids of kidney homogenates. The sensitivities to inhibitors of microsomal Acetohexamide reductase were different from those of cytosolic Acetohexamide reductase. Furthermore, streptozotocin-induced diabetes significantly decreased Acetohexamide reductase activity only in the kidney microsomes of male rats, resulting in the abolishment of the sex difference of Acetohexamide reduction by 10000 x g supernatant fluids of kidney homogenates.
Characterization of Acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors
J Biochem 1997 Apr;121(4):705-10.PMID:9163521DOI:10.1093/oxfordjournals.jbchem.a021643.
The structural requirements of Acetohexamide reductases purified from rabbit liver, kidney, and heart for substrates and inhibitors were examined. Acetohexamide, an oral antidiabetic drug with a ketone group, and analogs of it with various alkyl groups instead of the cyclohexyl group were used as substrates for these three enzymes. The results obtained as to substrate specificity suggested that the nature of the substrate-binding region of the heart enzyme is markedly different from those of the substrate-binding regions of the liver and kidney enzymes. Tolbutamide, which has no ketone group within its chemical structure, strongly inhibited the heart enzyme, whereas it had little ability to inhibit the liver or kidney enzyme. The inhibition of the heart enzyme by tolbutamide was competitive with respect to Acetohexamide and uncompetitive with respect to NADPH. Furthermore, tolbutamide analogs with n-pentyl and n-hexyl groups instead of the n-butyl group exhibited very pronounced inhibition of only the heart enzyme. Therefore, it is reasonable to postulate that the heart enzyme, unlike the liver and kidney ones, has a cleft of a strongly hydrophobic nature near its substrate-binding region, and that this hydrophobic cleft plays a critical role in the interaction of the heart enzyme with the cyclohexyl group of Acetohexamide.
Rabbit dehydrogenase/reductase SDR family member 11 (DHRS11): Its identity with Acetohexamide reductase with broad substrate specificity and inhibitor sensitivity, different from human DHRS11
Chem Biol Interact 2019 May 25;305:12-20.PMID:30926317DOI:10.1016/j.cbi.2019.03.026.
Human dehydrogenase/reductase SDR family member 11 (DHRS11) has been recently reported to be an NADP+-dependent 3(17)β-hydroxysteroid dehydrogenase, and its orthologs are predicted in genomic analyses of various animals. Among them, the amino acid sequence of predicted rabbit DHRS11 shares 92% identity with that of human DHRS11 and matches peptide sequences (composed of total 87 amino acids) of rabbit heart Acetohexamide reductase (RHAR) previously reported. However, the physiological role of RHAR remains unknown, because its known substrates are only Acetohexamide and 1,4-naphthoquinone. To elucidate whether the two rabbit enzymes are identical, we have isolated the cDNA for rabbit DHRS11, which was abundantly detected in the brain, heart, kidney and intestine by RT-PCR. The recombinant rabbit DHRS11 reduced Acetohexamide and 1,4-naphthoquinone, and was inhibited by tolbutamide and phenobarbital (RHAR-specific inhibitors), demonstrating its identity with RHAR. Rabbit DHRS11 also reduced α-dicarbonyl compounds, aldehydes and aromatic ketones (acetylbenzenes and acetylpyridines), and exhibited 3(17)β-hydroxysteroid dehydrogenase activity. It was competitively inhibited not only by tolbutamide and phenobarbital, but also more potently by several non-steroidal anti-inflammatory drugs such as diclofenac and sulindac. The broad substrate specificity and inhibitor sensitivity were different from those of human DHRS11, which did not reduce aliphatic aldehydes and aromatic ketones despite its higher 3(17)β-hydroxysteroid dehydrogenase activity, and was insensitive to tolbutamide, phenobarbital and diclofenac. The site-directed mutagenesis of Thr163 and Val200 in human DHRS11 to the corresponding residues (Gly and Leu, respectively) in rabbit DHRS11 suggested that these residues are pertinent to the differences in properties of rabbit and human DHRS11s.