(3S)-4-[[(3S,6S,9R,15S,18R,21S,24S)-3-[2-(2-aminophenyl)-2-oxoethyl]-24-(3-aminopropyl)-15,21-bis(carboxymethyl)-6-(1-carboxypropan-2-yl)-5,8,11,14,17,20,23,26,29-nonahydroxy-9-(hydroxymethyl)-18,31-dimethyl-2-oxo-1-oxa-4,7,10,13,16,19,22,25,28-nonazacyclohentriaconta-4,7,10,13,16,19,22,25,28-nonaen-30-yl]imino]-3-[[(2S)-1,4-dihydroxy-2-[[(2S)-1-hydroxy-2-(1-hydroxydecylideneamino)-3-(1H-indol-3-yl)propylidene]amino]-4-iminobutylidene]amino]-4-hydroxybutanoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3S)-4-[[(3S,6S,9R,15S,18R,21S,24S)-3-[2-(2-aminophenyl)-2-oxoethyl]-24-(3-aminopropyl)-15,21-bis(carboxymethyl)-6-(1-carboxypropan-2-yl)-5,8,11,14,17,20,23,26,29-nonahydroxy-9-(hydroxymethyl)-18,31-dimethyl-2-oxo-1-oxa-4,7,10,13,16,19,22,25,28-nonazacyclohentriaconta-4,7,10,13,16,19,22,25,28-nonaen-30-yl]imino]-3-[[(2S)-1,4-dihydroxy-2-[[(2S)-1-hydroxy-2-(1-hydroxydecylideneamino)-3-(1H-indol-3-yl)propylidene]amino]-4-iminobutylidene]amino]-4-hydroxybutanoic acid
• 化学式: C₇₂H₁₀₁N₁₇O₂₆
• 分子量: 1620.7
• InChiKey: DOAKLVKFURWEDJ-OFNKPWESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  115
• 可旋转键数：
  35
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  702
• 氢给体数：
  22
• 氢受体数：
  28

ADMET

毒理性

• 肝毒性

血清转氨酶水平升高发生在2%到6%接受达托霉素治疗的患者中，这个比率仅略高于安慰剂或对照药物。这些升高通常是轻到中度的，无症状且自限性，经常在不中断治疗甚至不停止治疗的情况下自行解决。有报道称，达托霉素可能导致孤立性肝损伤案例，但在大多数情况下血清胆红素正常，血清转氨酶升高是轻到中度的，并且通常伴有严重的肌肉损伤和显著的高肌酸激酶水平。没有黄疸或碱性磷酸酶升高的此类案例更有可能是由于肌肉而非肝脏损伤。尽管如此，仍有少数案例报告出现了轻度黄疸，血清酶升高呈肝细胞模式，肌酸激酶水平正常。发病潜伏期为5周，未出现免疫过敏和自身免疫特征，解决过程缓慢，6周后仍存在轻度异常。因此，临床上明显的达托霉素引起的肝损伤可能发生，但非常罕见。

Elevations in serum aminotransferase levels occur in 2% to 6% of patients receiving daptomycin, rates that are minimally higher than with placebo or comparator drugs. The elevations are generally mild-to-moderate, asymptomatic and self-limited, frequently resolving without discontinuation or even interruption of therapy. Isolated case reports of possible liver injury from daptomycin have been reported, but serum bilirubin was normal in most cases, and the serum aminotransferase elevations were mild-to-moderate and typically accompanied by severe muscle injury with marked CK elevations. Such cases without jaundice or alkaline phosphatase elevations are more likely due to muscle rather than liver injury. Nevertheless, a few case reports of mild jaundice with a hepatocellular pattern of serum enzyme elevations and normal CK levels has been published. The latency to onset was 5 weeks, immunoallergic and autoimmune features were not present, and resolution was slow with mild abnormalities still present 6 weeks later. Thus, clinically apparent liver injury from daptomycin probably occurs, but is quite rare.

来源:LiverTox

文献信息

• ANTI-WALL TEICHOIC ANTIBODIES AND CONJUGATES
  申请人：GENENTECH, INC.

  公开号：US20150366985A1

  公开（公告）日：2015-12-24

  The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

  这项发明提供了抗壁母细胞酸抗体及其抗生素结合物，以及使用它们的方法。
• Selective culture medium for polymyxin-resistant, gram-negative bacteria
  申请人：Université de Fribourg

  公开号：EP3072956A1

  公开（公告）日：2016-09-28

  The present invention concerns culture medium for specifically selecting gram-negative, aerobe bacteria that have an acquired resistance to polymyxins as well as bacteria that are naturally resistant to polymyxins. In particular, the culture medium allows selection of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii having an acquired resistance to polymyxins. Presently existing culture media select naturally resistant bacteria, but were found not to select bacteria that have an acquired resistance to polymyxins. The use of polymyxin antibiotics in humans has increased recently, as a last resort treatment against infections by multidrug resistant (MDR) bacteria. The present invention identifies and resolves the need for a diagnostic test for the identification and characterization of bacteria that have an acquired resistance to polymyxins as well.

  本发明涉及用于特异性选择对多粘菌素具有获得性抗性的革兰氏阴性气杆菌以及对多粘菌素具有天然抗性的细菌的培养基。特别是，这种培养基可以筛选出对多粘菌素具有获得性抗性的肠杆菌科细菌、铜绿假单胞菌和鲍曼不动杆菌。现有的培养基可以选择天然抗性细菌，但不能选择对多粘菌素有后天抗性的细菌。最近，多粘菌素抗生素在人类中的使用越来越多，作为治疗耐多药（MDR）细菌感染的最后手段。本发明确定并解决了对一种诊断测试的需求，该测试可用于识别和鉴定对多粘菌素具有获得性耐药性的细菌。
• ANTIBIOTISCHER POLYMETHYLMETHACRYLAT-KNOCHENZEMENT
  申请人：Heraeus Medical GmbH

  公开号：EP3184126A1

  公开（公告）日：2017-06-28

  Es wird ein antibiotischer Polymethylmethacrylat-Knochenzement vorgeschlagen, der aus Methylmethacrylat, mindestens einem Polymethylmethacrylat oder einem Polymethylmethacrylat-Copolymer, mindestens einem Polymerisationsinitiator, wie einem radikalischen Initiator, mindestens einem Polymerisationsbeschleuniger und mindestens einem Röntgenopaker zusammengesetzt ist, wobei die Komponenten in einer pulverförmigen Komponente und einer flüssigen Monomerkomponente oder in zwei bei Raumtemperatur pastenförmigen Komponenten vorliegen. Der erfindungsgemäße Polymethylmethacrylat-Knochenzement umfasst das cyclische Lipopeptid Daptomycin ein pharmakologisch verträgliches Salz von Daptomycin, ein Solvat und/oder ein Hydrat enthaltend Daptomycin und mindestens ein Calciumsalz, das vorzugsweise mindestens zwei unterschiedliche Freisetzungsprofile aufweist.

  本发明提出了一种抗生素聚甲基丙烯酸甲酯骨水泥，它由甲基丙烯酸甲酯、至少一种聚甲基丙烯酸甲酯或聚甲基丙烯酸甲酯共聚物、至少一种聚合引发剂（如自由基引发剂）、至少一种聚合促进剂和至少一种X射线不透明物组成，这些组分在室温下以粉末状组分和液态单体组分或两种糊状组分存在。根据本发明，聚甲基丙烯酸甲酯骨水泥包括环脂肽达托霉素、达托霉素的药理相容盐、含有达托霉素的溶液和/或水合物以及至少一种钙盐，其中钙盐最好具有至少两种不同的释放曲线。
• SKIN PERMEABLE PEPTIDE AND METHOD FOR USING SAME
  申请人：IUCF-HYU (Industry-University Cooperation Foundation Hanyang University)

  公开号：EP3336098A1

  公开（公告）日：2018-06-20

  The present disclosure is directed to providing a new skin-penetrating peptide, a fusion product with a biologically active substance bound using the same, a cosmetic composition containing the same and a pharmaceutical composition for external application to skin containing the same. The skin-penetrating peptide of the present disclosure is less likely to cause an immune response as compared to existing skin-penetrating peptides and exhibits remarkably improved skin permeability. Therefore, the biologically active substance can be effectively delivered through the skin, particularly through the stratum corneum.

  本公开旨在提供一种新的皮肤穿透肽、使用该肽与生物活性物质结合的融合产品、含有该肽的化妆品组合物以及含有该肽的用于皮肤外用的药物组合物。与现有的皮肤穿透肽相比，本公开的皮肤穿透肽引起免疫反应的可能性更小，而且皮肤渗透性显著提高。因此，生物活性物质可以有效地通过皮肤，特别是角质层输送。
• Skin-penetrating peptide and method for using same
  申请人：IUCF-HYU (INDUSTRY-UNIVERSITY COOPERATION FOUNDATION HANYANG UNIVERSITY)

  公开号：US10858395B2

  公开（公告）日：2020-12-08

  The present disclosure is directed to providing a new skin-penetrating peptide, a fusion product with a biologically active substance bound using the same, a cosmetic composition containing the same and a pharmaceutical composition for external application to skin containing the same. The skin-penetrating peptide of the present disclosure is less likely to cause an immune response as compared to existing skin-penetrating peptides and exhibits remarkably improved skin permeability. Therefore, the biologically active substance can be effectively delivered through the skin, particularly through the stratum corneum.

  本公开旨在提供一种新的皮肤穿透肽、使用该肽与生物活性物质结合的融合产品、含有该肽的化妆品组合物以及含有该肽的用于皮肤外用的药物组合物。与现有的皮肤穿透肽相比，本公开的皮肤穿透肽引起免疫反应的可能性更小，而且皮肤渗透性显著提高。因此，生物活性物质可以有效地通过皮肤，特别是角质层输送。