303-81-1

• 常用中文名：新生霉素
• 常用英文名：Novobiocin
• CAS号：303-81-1
• 分子式：C₃₁H₃₆N₂O₁₁
• 分子量：612.624
• 相关类别： 原料药 抗生素类药物 其它抗生素类药
• 发布时间：2018-05-13 08:00:00
• 更新时间：2024-01-02 16:42:50
• 新生霉素是一种有效的口服抗生素。新生霉素也是DNA回转酶抑制剂和热休克蛋白90(Hsp90)拮抗剂。新生霉素具有研究高度β-内酰胺耐药肺炎球菌感染的潜力。新生霉素具有抗正氧病毒活性[1][2][3][4][6]。

名称

• 中文名: 新生霉素
• 英文名: novobiocin
• 英文别名: Notonesomycin; (3R,4S,5R,6R)-5-Hydroxy-6-[(2-hydroxy-3-{[4-hydroxy-3-(3-methyl-2-buten-1-yl)benzoyl]amino}-8-methyl-4-oxo-4H-chromen-7-yl)oxy]-3-methoxy-2,2-dimethyltetrahydro-2H-pyran-4-yl carbamate (non-preferred name); Novobiocin

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 848.2±65.0 °C at 760 mmHg
• 熔点: 170-172°C (lit.)
• 分子式: C₃₁H₃₆N₂O₁₁
• 分子量: 612.624
• 闪点: 466.8±34.3 °C
• 精确质量: 612.231934
• PSA: 200.01000
• LogP: 2.37
• 蒸汽压: 0.0±3.3 mmHg at 25°C
• 折射率: 1.640
• 储存条件: 室温

生物活性

• 描述: 新生霉素是一种有效的口服抗生素。新生霉素也是DNA回转酶抑制剂和热休克蛋白90(Hsp90)拮抗剂。新生霉素具有研究高度β-内酰胺耐药肺炎球菌感染的潜力。新生霉素具有抗正氧病毒活性[1][2][3][4][6]。
• 相关类别:
  信号通路 >> 细胞凋亡 >> 细胞凋亡
  研究领域 >> 癌症
  信号通路 >> 代谢酶/蛋白酶 >> HSP
  研究领域 >> 感染
  信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成
  信号通路 >> 细胞周期/DNA损伤 >> HSP
  信号通路 >> 抗感染 >> 细菌
• 靶点:

  HSP90

• 体外研究: 新生霉素(1mM)竞争性地抑制ATP与回转酶B的结合,以干扰核苷酸结合,并干扰共伴侣Hsc70和p23与Hsp90的结合[1]。新生霉素(200µM；24小时)抑制顺式DDP和BCNU诱导的DNA链间交联的修复率,并相应降低人类多形性胶质母细胞瘤细胞的克隆形成存活率[2]。新生霉素(0.3 mM；48小时)通过诱导K562、HL60和Mutz-2中约三至五倍的凋亡细胞,诱导caspase-3/7酶依赖性凋亡测定[5]。
• 体内研究: 新生霉素(25、50、100、200 mg/kg；皮下注射；感染后1、5、24和48小时注射4次)在感染耐阿莫西林肺炎链球菌的小鼠中显示出抗感染活性[3]。动物模型：30g成年雌性瑞士小鼠(由青霉素敏感菌株(AR33118)诱导的脓毒症)[3]剂量：25、50、100、200mg/kg给药：皮下注射。；在感染后1、5、24和48小时给予结果：在感染耐阿莫西林肺炎链球菌的小鼠中显示抗感染活性。
• 参考文献:

  [1]. Marcu MG, et al. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J Biol Chem. 2000 Nov 24;275(47):37181-6.

  [2]. Ali-Osman F, et al. Topoisomerase II inhibition and altered kinetics of formation and repair of nitrosourea and cisplatin-induced DNA interstrand cross-links and cytotoxicity in human glioblastoma cells. Cancer Res. 1993 Dec 1;53(23):5663-8.

  [3]. Rodríguez-Cerrato V, et al. Comparative efficacy of novobiocin and amoxicillin in experimental sepsis caused by beta-lactam-susceptible and highly resistant pneumococci. Int J Antimicrob Agents. 2010 Jun;35(6):544-9.

  [4]. Eder JP, et al. A phase I clinical trial of novobiocin, a modulator of alkylating agent cytotoxicity. Cancer Res. 1991 Jan 15;51(2):510-3.

  [5]. Bhatia S, et al. Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response.Blood. 2018 Jul 19;132(3):307-320.

  [6]. Smee DF. Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. Antivir Chem Chemother. 2008;19(3):115-24.

  [7]. Smee DF. Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. Antivir Chem Chemother. 2008;19(3):115-24.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : CU9080000 CHEMICAL NAME : Benzamide, N-(7-((3-O-(aminocarbonyl)-6-deoxy-5-C-methyl-4-O-met hyl-beta-L-lyxo- hexopyranosyl)oxy)-4-hydroxy-8-methyl-2-oxo-2H-1-benz opyran-3-yl)-4-hydrox y- 3-(3-methyl-2-butenyl)- CAS REGISTRY NUMBER : 303-81-1 LAST UPDATED : 199410 DATA ITEMS CITED : 20 MOLECULAR FORMULA : C31-H36-N2-O11 MOLECULAR WEIGHT : 612.69 WISWESSER LINE NOTATION : T66 BOVJ DMVR DQ C2UY1&1& EQ J1 IO- FT6OTJ B1 B1 CV1 DOVZ EQ &-NA- HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human DOSE/DURATION : 171 mg/kg/12D-C TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - conjunctive irritation Skin and Appendages - dermatitis, other (after systemic exposure) TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 262 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 407 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : Cytogenetic analysis MUTATION DATA TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Rodent - hamster Ovary DOSE/DURATION : 200 mg/L REFERENCE : CHROAU Chromosoma. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1939- Volume(issue)/page/year: 85,603,1982

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302-H317
• 警示性声明: P280-P301 + P312 + P330
• 危害码 (欧洲): Xi
• 危险品运输编码: NONH for all modes of transport

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