Caracemide
(Synonyms: 卡醋胺,NSC-253272) 目录号 : GC38896
Caracemide (NSC-253272) 可以抑制大肠杆菌的核糖核苷酸还原酶。Caracemide是衍生自异羟肟酸的新型抗癌药，会产生严重的中枢神经系统 (CNS) 毒性。
Cas No.:81424-67-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Caracemide (NSC-253272) inhibits the enzyme ribonucleotide reductase of Escherichia coli. Caracemide is a novel anticancer agent derived from a hydroxamic acid and has demonstrated to produce severe central nervous system (CNS) toxicity[1][2].
Caracemide inactivates R1 by covalent modification at the substrate-binding site and has a toxic metabolite, methylisocyanate (MIC), in vivo[1][2].
The mercapturic acid derivative AMCC was identified in urine rats following administration to rats of a single i.p. dose (6.6 mg/kg) of caracemide (NSC-253272)[1]. .
[1]. Slatter JG, et al. Studies on the metabolic fate of caracemide, an experimental antitumor agent, in the rat. Evidence for the release of methyl isocyanate in vivo. Chem Res Toxicol. 1993 May-Jun;6(3):335-40. [2]. Larsen IK, et al. Caracemide, a site-specific irreversible inhibitor of protein R1 of Escherichia coli ribonucleotide reductase. J Biol Chem. 1992 Jun 25;267(18):12627-31.
| Cas No. | 81424-67-1 | SDF | |
| 别名 | 卡醋胺,NSC-253272 | ||
| Canonical SMILES | CC(N(OC(NC)=O)C(NC)=O)=O | ||
| 分子式 | C6H11N3O4 | 分子量 | 189.17 |
| 溶解度 | Soluble in DMSO | 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 | 5.2863 mL | 26.4313 mL | 52.8625 mL |
| 5 mM | 1.0573 mL | 5.2863 mL | 10.5725 mL |
| 10 mM | 0.5286 mL | 2.6431 mL | 5.2863 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。
Caracemide, a site-specific irreversible inhibitor of protein R1 of Escherichia coli ribonucleotide reductase
J Biol Chem 1992 Jun 25;267(18):12627-31.PMID:1618768doi
The anticancer drug Caracemide, N-acetyl-N,O- di(methylcarbamoyl)hydroxylamine, and one of its degradation products, N-acetyl-O-methylcarbamoyl-hydroxylamine, were found to inhibit the enzyme ribonucleotide reductase of Escherichia coli by specific interaction with its larger component protein R1. No effect on the smaller protein R2 was observed. The effect of the degradation product was about 30 times lower than that of Caracemide itself. The Caracemide inactivation of R1 is irreversible, with an apparent second-order rate constant of 150 M-1 s-1. The R1R2 holoenzyme was approximately 30 times more sensitive to Caracemide inactivation than the isolated R1 protein. The ribonucleotide reductase substrates were potent competitors of the Caracemide inhibition, with a Kdiss for GDP binding to R1 of 80 microM. The reducing agent dithiothreitol was also found to be a potent competitor of Caracemide inactivation. These results indicate that Caracemide inactivates R1 by covalent modification at the substrate-binding site. By analogy with the known interaction between Caracemide and acetylcholinesterase or choline acetyltransferase, we propose that the modification of R1 occurs at an activated cysteine or serine residue in the active site of the enzyme.
Biochemical pharmacology of N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea (Caracemide; NSC-253272)
Biochem Pharmacol 1986 Aug 15;35(16):2781-7.PMID:3527174DOI:10.1016/0006-2952(86)90190-5.
Preclinical pharmacologic studies of Caracemide [N-acetyl-N-(methylcarbamoyloxy)-N'-methylurea; CAR] have demonstrated a marked instability of this compound in the presence of either phosphate buffer (pH 7.4) or human plasma. Using [1-14C-acetyl]CAR and [3H-methylcarbamoyloxy]CAR, three CAR degradation products were identified: product A, N-(methylcarbamoyloxy)acetamide; product B: N-(methylcarbamoyloxy)-N'-methylurea; and product C: N-hydroxy-N'-methylurea. CAR degradation in human plasma was demonstrated by high-performance liquid chromatography (HPLC) to occur in a time- and temperature-dependent manner. A 30-min incubation (37 degrees) of CAR (10(-4) M) with human plasma resulted in degradation of more than 55% of parent compound; at 1 hr, more than 75% of original CAR was degraded. Incubation of [1-14C-acetyl]CAR with rat brain homogenate resulted in the formation of 14CO2. This reaction was partially inhibited by coincubation with physostigmine (10(-3) M). CAR inhibited acetylcholinesterase activity in neuroblastoma cells with an IC50 of 14 microM. In mechanism of action studies, CAR was found to inhibit ribonucleotide reductase activity but only at nine times the IC50 of hydroxyurea. In contrast to hydroxyurea, CAR was found to be non-cell-cycle phase-specific and non-cross-resistant with two CHO cell lines resistant to hydroxyurea. These data demonstrate the instability of CAR; moreover, they suggest that its mechanism of cytotoxicity is distinctly different from that of hydroxyurea and that the neurotoxicity associated with CAR administration may be caused in part by inhibition of acetylcholinesterase activity.
Studies on the metabolic fate of Caracemide, an experimental antitumor agent, in the rat. Evidence for the release of methyl isocyanate in vivo
Chem Res Toxicol 1993 May-Jun;6(3):335-40.PMID:8318655DOI:10.1021/tx00033a013.
Following administration to rats of a single ip dose (6.6 mg kg-1) of the investigational antitumor agent Caracemide (N-acetyl-N,O-bis[methylcarbamoyl]hydroxylamine), the mercapturic acid derivative N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) was identified in urine by thermospray LC-MS. Quantification of this conjugate was carried out by stable isotope dilution thermospray LC-MS, which indicated that the fraction of the Caracemide dose recovered as AMCC in 24-h urine collections was 54.0 +/- 5.5% (n = 4). Since AMCC is known to represent a major urinary metabolite of methyl isocyanate (MIC) in the rat, the results of this study support the contention that Caracemide yields MIC as a toxic intermediate in vivo. Furthermore, with the aid of a specifically deuterium-labeled analog of Caracemide ([carbamoyloxy-C2H3]Caracemide), it was shown that the methylcarbamoyl group of AMCC derived from both the O-methylcarbamoyl (72%) and N-methylcarbamoyl (28%) side chains of the drug. In view of these findings, it is concluded that Caracemide acts as a latent form of MIC in vivo and that this reactive isocyanate (or labile S-linked conjugates thereof) may contribute to the antitumor properties and/or adverse side-effects of Caracemide.
A phase II trial of amonafide, Caracemide, and homoharringtonine in the treatment of patients with advanced renal cell cancer
Invest New Drugs 1996;14(4):409-13.PMID:9157078DOI:10.1007/BF00180819.
Forty-eight previously untreated, ambulatory patients with advanced or unresectable renal carcinoma were treated with either amonafide (17 patients), Caracemide (17 patients), or homoharringtonine (14 patients). No objective responses were observed in any of the treatment cohorts. Amonafide and Caracemide were well tolerated with no unexpected toxicities. One patient each died of pulmonary thromboembolism and sepsis with severe metabolic acidosis on the homoharringtonine arm. An additional 4 patients experienced grade 4 complications including myelosuppression, neurologic dysfunction, and respiratory failure. These severe and unexpected complications caused early termination of accrual to the homoharringtonine arm of the study. These agents have no activity in the treatment of advanced renal cell carcinoma.
Release of methyl isocyanate from the antitumor agent Caracemide (NSC-253272)
Invest New Drugs 1987;5(3):267-71.PMID:3667162DOI:10.1007/BF00175297.
In recent phase 1 clinical trials, Caracemide [N-acetyl-N-(methylcarbamoyloxy)-N-methylurea; NSC-253272] has demonstrated a marked potential to produce severe central nervous system (CNS) toxicity. Recent in vitro studies of this antitumor agent have presented indirect evidence indicating that methyl isocyanate is a likely metabolite which results from incubation of Caracemide with either phosphate buffer or human plasma. This report presents evidence that methyl isocyanate is formed from Caracemide in a concentration- and time-dependent manner. These data implicate the caracemide-mediated formation of methyl isocyanate as at least a plausible explanation for the CNS toxicity exhibited by this drug.