Cytembena | 21739-91-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Cytembena
• 英文别名: sodium;(E)-3-bromo-4-(4-methoxyphenyl)-4-oxobut-2-enoate
• CAS: 21739-91-3
• 化学式: C11H8BrNaO4
• 分子量: 307.07
• InChiKey: DVDCIQWIGOVWEX-MLBSPLJJSA-M

物化性质

• 物理描述：
  Cytembena is a white to off-white powder. (NTP, 1992)
• 熔点：
  500 to 505 °F (NTP, 1992)
• 溶解度：
  50 to 100 mg/mL at 70° F (NTP, 1992)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.09
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

CYTEMBENA被兔肝微粒体脱甲基，并在存在还原型谷胱甘肽和NADPH的情况下，通过100,000-G上清液组分去溴化并饱和。通过质谱法初步鉴定了代谢物的结构。

CYTEMBENA WAS DEMETHYLATED BY RABBIT LIVER MICROSOMES & WAS DEBROMINATED & SATURATED BY 100,000-G SUPERNATANT FRACTION IN PRESENCE OF GLUTATHIONE & NADPH. STRUCTURES OF METABOLITES TENTATIVELY IDENTIFIED BY MASS SPECTROMETRY.

来源:Hazardous Substances Data Bank (HSDB)

代谢

CYTEMBENA与包括谷胱甘肽和半胱氨酸在内的硫醇化合物迅速发生反应，导致硫的烷基化。CYTEMBENA和谷胱甘肽的产物被分离并测试了其细胞毒性；它不如自由的CYTEMBENA有效。这个反应可能是一种解毒过程。

CYTEMBENA UNDERGOES RAPID REACTION WITH THIOL COMPD INCL GLUTATHIONE & CYSTEINE, RESULTING IN ALKYLATION OF SULFUR. PRODUCT OF CYTEMBENA & GLUTATHIONE WAS ISOLATED & TESTED FOR CYTOTOXICITY; IT WAS LESS EFFECTIVE THAN FREE CYTEMBENA. REACTION MAY BE DETOXIFICATION PROCESS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

17例对3期和4期烷化剂有抗性的卵巢癌患者接受了塞特本纳治疗，剂量为200毫克/平方米，每天两次，每5天为一个周期。除了1名患者外，所有患者都出现了恶心和呕吐，其中3名患者有轻度腹泻，2名患者出现了脱发。

17 PT WITH STAGES 3 & 4 ALKYLATING AGENT RESISTANT OVARIAN CARCINOMAS WERE TREATED WITH CYTEMBENA IN DOSES OF 200 MG/SQ M TWICE DAILY FOR 5 DAYS EVERY 5 WK. NAUSEA & VOMITING OCCURRED IN ALL EXCEPT 1 PT, & 3 PT HAD MILD DIARRHEA. 2 HAD ALOPECIA.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

22 PT连续5天每天接受静脉注射。毒性随剂量增加而显著，在300毫克/平方米时变得突出；出现恶心和呕吐。在475毫克/平方米的剂量下，出现了高血压、心动过速、胸痛和心电图变化。

22 PT RECEIVED DAILY IV INJECTIONS FOR 5 DAYS. TOXICITY WAS DOSE RELATED, BECOMING PROMINENT @ 300 MG/SQ M; NAUSEA & VOMITING WERE SEEN. HYPERTENSION, TACHYCARDIA, CHEST PAIN, & ECG CHANGES OCCURRED @ DOSES OF 475 MG/SQ M.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

30名组织学上证实为晚期卵巢或乳腺癌的女性患者接受了赛替麦本治疗，剂量为每天250毫克/平方米，连续5天，每周重复一次。没有发现造血毒性。恶心、呕吐和自主神经风暴现象是限制剂量的因素。

30 WOMEN WITH HISTOLOGICALLY PROVEN ADVANCED OVARIAN OR BREAST CANCER WERE TREATED WITH CYTEMBENA, DOSE OF 250 MG/SQ M/DAY FOR 5 DAYS REPEATED @ WEEKLY INTERVALS. NO HEMOPOIETIC TOXICITY. NAUSEA & VOMITING & AUTONOMIC STORM PHENOMENON ARE DOSE-LIMITING FACTORS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

多种恶性肿瘤患者接受了20毫克/千克的赛特本钠静脉注射。赛特本钠治疗24小时后，异常中期的频率和染色体断裂的情况较低。

PT WITH VARIOUS TYPES OF MALIGNANCY RECEIVED 20 MG CYTEMBENA/KG, IV. THE FREQUENCY OF ABNORMAL METAPHASES & CHROMOSOMAL BREAKS 24 HR AFTER CYTEMBENA TREATMENT WAS LOW.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

长期静脉注射12.5-200毫克/千克/天和6.25-50毫克/千克/天的药物在狗和猴子身上损害了远端肾小管，并且耗尽了淋巴组织的生殖细胞元素；在高剂量下产生了呕吐、厌食和体重减轻。在猴子身上还观察到了骨髓和肝脏的涉及。

CHRONIC IV ADMIN OF 12.5-200 & 6.25-50 MG/KG/DAY IN DOGS & MONKEYS DAMAGED DISTAL RENAL TUBULES, & DEPLETED GERMINAL CELLULAR ELEMENTS OF LYMPHOID TISSUES; @ HIGH DOSES PRODUCED EMESIS, ANOREXIA, & WT LOSS. BONE MARROW & LIVER INVOLVEMENT NOTED IN MONKEYS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在正常受试者中，单次静脉注射200毫克后15小时内，肾脏排泄量约为给药剂量的7.8%。在肾功能受损的患者中，尿液排泄量较少，并且与内生肌酐清除率下降直接相关。

IN NORMAL SUBJECTS RENAL EXCRETION WAS APPROX 7.8% OF GIVEN DOSE IN 15 HR FOLLOWING SINGLE IV INJECTION OF 200 MG. IN PT WITH IMPAIRED RENAL FUNCTION, URINARY EXCRETION WAS LESS & DIRECTLY CORRELATED WITH DECR IN ENDOGENOUS CREATININE CLEARANCE RATE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当给予14C标记的赛特明钠时，大鼠在24小时内排泄了超过70%，狗排泄了超过50%的放射性剂量；大部分标记物在尿液中找到。24小时后，肾脏保留了最高的放射性水平。

WHEN (14)C-LABELED CYTEMBENA WAS ADMIN, RATS EXCRETED GREATER THAN 70% & DOGS GREATER THAN 50% OF RADIOACTIVE DOSE IN 24 HR; MOST OF LABEL WAS FOUND IN URINE. KIDNEY RETAINED HIGHEST LEVEL OF RADIOACTIVITY AFTER 24 HR.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2918990090