(3E,5E,7R,8S,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-4-[(2R,4R,5S,6R)-2,4-dihydroxy-5-methyl-6-propan-2-yloxan-2-yl]-3-hydroxypentan-2-yl]-8-hydroxy-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraen-2-one | 88899-55-2

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 抗真菌类药
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (3E,5E,7R,8S,9S,11E,13E,15S,16R)-16-[(2S,3R,4S)-4-[(2R,4R,5S,6R)-2,4-dihydroxy-5-methyl-6-propan-2-yloxan-2-yl]-3-hydroxypentan-2-yl]-8-hydroxy-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraen-2-one
• CAS: 88899-55-2
• 化学式: C₃₅H₅₈O₉
• 分子量: 622.8
• InChiKey: XDHNQDDQEHDUTM-DYKYWCSGSA-N

物化性质

• 熔点：
  >106°C (dec.)
• 沸点：
  582.86°C (rough estimate)
• 密度：
  1.0594 (rough estimate)
• 闪点：
  87℃
• 溶解度：
  溶于 DMSO（高达 5 mg/ml，加热）。

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  9

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  29419090
• 危险品运输编号：
  UN 3172
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险性防范说明：
  P201,P202,P264,P270,P280,P301+P312+P330,P308+P313,P405,P501
• 危险性描述：
  H302,H340,H350,H360

制备方法与用途

生物活性

巴利福霉素A1（Baf-A1）是一种液泡H+-ATPase抑制剂，IC50值为0.44 nM。研究表明，巴利福霉素A1能够抑制自噬并诱导凋亡。

靶点

Target	Value
H+-ATPase (Cell-free assay)	0.44 nM

体外研究

巴利福霉素A1是一种源自灰色链霉菌的有毒的大环内酯类抗生素。该化合物能够抑制外套膜上皮细胞（OME）诱导的短路电流，其IC50值为0.17 μM，最大抑制剂量为0.5 μM。此外，它还能够抑制酸内流，IC50值为0.4 nM，并且以剂量依赖性方式抑制酸化，导致较低的淬灭和更高的荧光性。

巴利福霉素A1能够防止幽门螺杆菌（H. pylori）细胞诱导的HeLa细胞空泡化，其ID50值为4 nM。该化合物还能有效恢复空泡细胞至正常形态，并影响内吞物质从早期到晚期内吞区的转运过程，在HeLa细胞中不仅消耗较低的内体pH，还会阻断从早期到晚期内体的转运。

在BNL CL.2 和 A431细胞中，与吖啶橙共培养表明巴利福霉素A1在0.1-1 μM剂量下完全抑制溶酶体酸化。当将巴利福霉素A1加入Hanks平衡盐溶液时，内源性蛋白质降解被强烈抑制，并且众多自噬体会聚集在H-4-II-E细胞中。此外，该化合物还能防止自噬泡中吞饮HRP的出现。

体内研究

巴利福霉素A1（1 μM和0.1 μM）完全抑制培养的破骨细胞的再摄取活性。剂量依赖性地抑制年轻罗非鱼体内的钠离子吸收，Ki值为0.16 μM。

文献信息

• Optimized Method for Treating and Curing Arthritis, Diabetes, Multiple Sclerosis and Other Autoimmune Disease
  申请人：Postrel Richard

  公开号：US20190070166A1

  公开（公告）日：2019-03-07

  The present invention teaches a method, system and process for curing, treating and diagnosing arthritis, diabetes and other related autoimmune diseases. By intercepting and mitigating the disease process at the point of origination prevents the disease from developing and stops the lineage of cells causing disease symptoms. This fundamental system addresses cellular events where the immune reaction is emerging thereby preventing advance of the cascade that feeds the disease. Modulating activity of the errant protein at this initiating point in the immune response blocks the autoimmune cascade and prevents formation of secondary and tertiary effects that will characterize the disease. As the cascade progresses, the number of participating enzymes and pathways compounds so that each progression step further from the initiation point requires increasingly complex therapies. Thus, by treating the primary cause, secondary and tertiary symptoms do not appear. This avoids the side effects observed in multi-faceted approaches presently used to manage the disease symptoms rather than disease causation.
• COMBINATORY TREATMENT STRATEGIES OF CANCER BASED ON RNA POLYMERASE I INHIBITION
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20190247397A1

  公开（公告）日：2019-08-15

  Disclosed herein are compositions comprising a combination of at least one Pol I inhibitor, and at least one autophagy inhibiting compound, and/or at least one ACAT1 inhibiting compound, and/or at least one PARP inhibiting compound and their use in treating cancers and other related neoplastic diseases and which may also include additional chemotherapeutic agents.
• [EN] METHODS AND COMPOSITIONS FOR SENSITIZING CANCER CELLS TO DRUG-INDUCED APOPTOSIS<br/>[FR] MÉTHODES ET COMPOSITIONS POUR SENSIBILISER LES CELLULES CANCÉREUSES À UNE APOPTOSE INDUITE PAR UN MÉDICAMENT
  申请人：UNIV NEW YORK

  公开号：WO2020223609A1

  公开（公告）日：2020-11-05

  Disclosed herein are methods of increasing the sensitivity of cancer cells to cell death by an apoptosis-inducing drug. Also disclosed herein are methods of treating cancer in a subject and combination therapeutics.