Drug Details

General Information of the Drug (ID: DR3681)
Name
Depsipeptide
Synonyms
Chromadax; Istodax; Antibiotic FR 901228; FK 228; FK228; FR 901228; FR901228; HDInhib_000006; Chromadax (TN); FK-228; FK-901228; FR-901228; Istodax (TN); Romidepsin (USAN); Cyclo((2Z)-2-amino-2-butenoyl-L-valyl-(3S,4E)-3-hydroxy-7-mercapto-4-heptenoyl-D-valyl-D-cysteinyl), cyclic (35)-disulfide; L-Valine, N-((3S,4E)-3-hydroxy-7-mercapto-1-oxo-4-heptenyl)-D-valyl-D-cysteinyl-(2Z)-2-amino-2-butenoxyl-, (4-1)-lactone, cyclic (1-2)-disulfide; (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; (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone; (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone
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Molecular Type
Small molecule
Disease Mycosis fungoides [ICD-11: 2B01] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C24H36N4O6S2
PubChem CID
5352062
Canonical SMILES
CC=C1C(=O)NC(C(=O)OC2CC(=O)NC(C(=O)NC(CSSCCC=C2)C(=O)N1)C(C)C)C(C)C
InChI
1S/C24H36N4O6S2/c1-6-16-21(30)28-20(14(4)5)24(33)34-15-9-7-8-10-35-36-12-17(22(31)25-16)26-23(32)19(13(2)3)27-18(29)11-15/h6-7,9,13-15,17,19-20H,8,10-12H2,1-5H3,(H,25,31)(H,26,32)(H,27,29)(H,28,30)/b9-7+,16-6-/t15-,17-,19-,20+/m1/s1
InChIKey
OHRURASPPZQGQM-GCCNXGTGSA-N
CAS Number
CAS 128517-07-7
TTD Drug ID
D0L7LC
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Flavopiridol      Dysoxylum binectariferum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP9  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
                    In-vitro Model NCI-H322 CVCL_1556 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
TE-12 CVCL_1762 Esophageal squamous cell carcinoma Homo sapiens
TE-13 CVCL_4463 Esophageal squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The depsipeptide plus flavopiridol combination exhibits powerful and selective cytocidal activity against cancer but not normal cells. Apoptosis induced by this combination is mediated by the mitochondria-dependent death pathway.
Target and Pathway
Target(s) Histone deacetylase 1 (HDAC1)  Molecule Info  [3]
KEGG Pathway Cell cycle Click to Show/Hide
2 Notch signaling pathway
3 Thyroid hormone signaling pathway
4 Huntington's disease
5 Amphetamine addiction
6 Alcoholism
7 Epstein-Barr virus infection
8 Pathways in cancer
9 Transcriptional misregulation in cancer
10 Viral carcinogenesis
11 MicroRNAs in cancer
12 Chronic myeloid leukemia
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
Panther Pathway Wnt signaling pathway Click to Show/Hide
2 p53 pathway
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling Click to Show/Hide
2 Notch signaling pathway
3 E2F transcription factor network
4 Presenilin action in Notch and Wnt signaling
5 Signaling events mediated by HDAC Class I
6 Regulation of Telomerase
7 Glucocorticoid receptor regulatory network
8 Sumoylation by RanBP2 regulates transcriptional repression
9 Regulation of Androgen receptor activity
10 IL3-mediated signaling events
11 Validated nuclear estrogen receptor alpha network
12 Retinoic acid receptors-mediated signaling
13 Hedgehog signaling events mediated by Gli proteins
14 Regulation of nuclear beta catenin signaling and target gene transcription
15 Validated targets of C-MYC transcriptional repression
16 Regulation of retinoblastoma protein
17 Notch-mediated HES/HEY network
Reactome G0 and Early G1 Click to Show/Hide
2 p75NTR negatively regulates cell cycle via SC1
3 Formation of the beta-catenin:TCF transactivating complex
4 NOTCH1 Intracellular Domain Regulates Transcription
5 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
6 Constitutive Signaling by NOTCH1 PEST Domain Mutants
7 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
8 HDACs deacetylate histones
9 Deactivation of the beta-catenin transactivating complex
10 NoRC negatively regulates rRNA expression
11 RNA Polymerase I Transcription Initiation
12 Factors involved in megakaryocyte development and platelet production
WikiPathways SIDS Susceptibility Pathways Click to Show/Hide
2 Notch Signaling Pathway
3 TGF beta Signaling Pathway
4 IL-6 signaling pathway
5 Apoptosis-related network due to altered Notch3 in ovarian cancer
6 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
7 Notch Signaling Pathway
8 Retinoblastoma (RB) in Cancer
9 Neural Crest Differentiation
10 TWEAK Signaling Pathway
11 Integrated Breast Cancer Pathway
12 Signalling by NGF
13 RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription
14 Mitotic G1-G1/S phases
15 Factors involved in megakaryocyte development and platelet production
16 Cell Cycle
17 Androgen receptor signaling pathway
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7006).
Reference 2 Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: activation of the mitochondria-dependent death-signaling pathway. J Thorac Cardiovasc Surg. 2003 May;125(5):1132-42.
Reference 3 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
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