FR-135313 | 390745-19-4

• 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: FR-135313
• 英文别名: romidepsin；romedepsin；Romidepsin reduced；(3S,6Z,9S,12R,16S)-6-ethylidene-3,12-di(propan-2-yl)-16-[(E)-4-sulfanylbut-1-enyl]-9-(sulfanylmethyl)-1-oxa-4,7,10,13-tetrazacyclohexadecane-2,5,8,11,14-pentone
• CAS: 390745-19-4
• 化学式: C₂₄H₃₈N₄O₆S₂
• 分子量: 542.721
• InChiKey: MEJLVLMAJJRLCR-GCCNXGTGSA-N

物化性质

• 沸点：
  926.8±65.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  145
• 氢给体数：
  6
• 氢受体数：
  8

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	romidepsin	128517-07-7	C24H36N4O6S2	540.705

反应信息

• 作为反应物：
  描述：

  FR-135313 在 三乙胺 作用下， 以 甲醇 为溶剂， 以35.6%的产率得到
  参考文献：
  名称：

  Metabolite derivatives of the HDAC inhibitor FK228

  摘要：

  本发明涉及HDAC抑制剂衍生物，特别是FK228的代谢物的游离巯基衍生物，以及其药物组合物，以及使用这些衍生物和药物组合物治疗与HDAC相关的疾病的方法，特别是肿瘤或细胞增殖性疾病。

  公开号：

  US20070129290A1
• 作为产物：
  描述：

  romidepsin 在 DL-dithiothreitol 作用下， 以 甲醇 为溶剂， 以90.6%的产率得到FR-135313
  参考文献：
  名称：

  Metabolite derivatives of the HDAC inhibitor FK228

  摘要：

  本发明涉及HDAC抑制剂衍生物，特别是FK228的代谢物的游离巯基衍生物，以及其药物组合物，以及使用这些衍生物和药物组合物治疗与HDAC相关的疾病的方法，特别是肿瘤或细胞增殖性疾病。

  公开号：

  US20070129290A1

文献信息

• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF (1S, 4S, 7Z, 10S, 16E, 21R)- 7-ETHYLIDENE-4,21-BIS(1-METHYLETHYL)-2-OXA-12,13-DITHIA-5, 8, 20, 23- TETRAAZABICYCLO[8.7.6]TRICOS-16-ENE-3, 6, 9, 19, 22-PENTONE<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE (1S, 4S, 7Z, 10S, 16E, 21R)- 7-ÉTHYLIDÈNE-4,21-BIS(1-MÉTHYLÉTHYL)-2-OXA-12,13-DITHIA-5, 8, 20, 23- TÉTRAAZABICYCLO[8.7.6]TRICOS-16-ÈNE-3, 6, 9, 19, 22-PENTONE
  申请人：MSN LABORATORIES PRIVATE LTD

  公开号：WO2017068596A1

  公开（公告）日：2017-04-27

  The present invention is relates to an improved process for the preparation (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1-methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabi-cyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone of formula I.

  本发明涉及一种改进的制备过程，用于制备式I的(1S,4S,7Z,10S,16E,21R)-7-乙烯基-4,21-双(1-甲基乙基)-2-氧-12,13-二硫-5,8,20,23-四氮杂环[8.7.6]三十一烯-16-烯-3,6,9,19,22-五酮。
• Thailandepsins: Bacterial Products with Potent Histone Deacetylase Inhibitory Activities and Broad-Spectrum Antiproliferative Activities
  作者：Cheng Wang、Leonhard M. Henkes、Leah B. Doughty、Min He、Difei Wang、Franz-Josef Meyer-Almes、Yi-Qiang Cheng

  DOI：10.1021/np200324x

  日期：2011.10.28

  Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer drugs, with one synthetic compound, SAHA (vorinostat, Zolinza; 1), and one natural product, FK228 (depsipeptide, romidepsin, Istodax; 2), approved by FDA for clinical use. Our studies of FK228 biosynthesis in Chromobacterium violaceum no. 968 led to the identification of a cryptic biosynthetic gene cluster in the genome of Burkholderia thailandensis E264. Genome mining and genetic manipulation of this gene cluster further led to the discovery of two new products, thailandepsin A (6) and thailandepsin B (7). HDAC inhibition assays showed that thailandepsins have selective inhibition profiles different from that of FK228, with comparable inhibitory activities to those of FK228 toward human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC9 but weaker inhibitory activities than FK228 toward HDAC4 and HDAC8, the latter of which could be beneficial. NCI-60 anticancer screening assays showed that thailandepsins possess broad-spectrum antiproliferative activities with GI(50) for over 90% of the tested cell lines at low nanomolar concentrations and potent cytotoxic activities toward certain types of cell lines, particularly for those derived from colon, melanoma, ovarian, and renal cancers. Thailandepsins thus represent new naturally produced HDAC inhibitors that are promising for anticancer drug development.
• The Contribution of Romidepsin to the Herbicidal Activity of <i>Burkholderia rinojensis</i> Biopesticide
  作者：Daniel K. Owens、Joanna Bajsa-Hirschel、Stephen O. Duke、Caio A. Carbonari、Giovanna L. G. C. Gomes、Ratnakar Asolkar、Louis Boddy、Franck E. Dayan

  DOI：10.1021/acs.jnatprod.9b00405

  日期：2020.4.24

  The culture broth of Burkholderia rinojensis strain A396 is herbicidal to a number of weed species with greater observed efficacy against broadleaf than grass weeds. A portion of this activity is attributed to romidepsin, a 16-membered cyclic depsipeptide bridged by a 15-membered macrocyclic disulfide. Romidepsin, which is present in small amounts in the broth (18 to 25 mu g mL(-1)), was isolated and purified using standard chromatographic techniques. It was established that romidepsin is a natural proherbicide that targets the activity of plant histone deacetylases (HDAC). Assays to measure plant HDAC activity were optimized by testing a number of HDAC substrates. The activity of romidepsin was greater when its macrocyclic-forming disulfide bridge was reduced to liberate a highly reactive free butenyl thiol side chain. Reduction was achieved using 200 mM tris(2-carboxyethyl)phosphine hydrochloride. A similar bioactivation of the proherbicide via reduction of the disulfide bridge of romidepsin was observed in plant-cell-free extracts. Molecular dynamic simulation of the binding of romidepsin to Arabidopsis thaliana HDAC19 indicated the reduced form of the compound could reach deep inside the catalytic domain and interact with an associated zinc atom required for enzyme activity.
• COMBINATION THERAPY FOR CHEMORESISTANT CANCERS
  申请人：CELGENE CORPORATION

  公开号：US20130244950A1

  公开（公告）日：2013-09-19

  Methods of treating, preventing or managing triple negative breast cancer (TNBC) or clear cell renal cell carcinoma (ccRCC) are disclosed. The methods encompass the administration of an HDAC inhibitor romidepsin in combination with a cytidine analog. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods provided herein are also disclosed.
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.