Drug Information

Drug (ID: DG00176) and It's Reported Resistant Information
Name
Vorinostat
Synonyms
NHNPODA; SAHA; SHH; Zolinza; Merck brand of Vorinostat; OCTANEDIOIC ACID HYDROXYAMIDE PHENYLAMIDE; SAHA cpd; Suberanilohydroxamic acid; Suberoylanilide hydroxamic acid; Vorinostat MSD; Vorinostat [USAN]; M344; MK0683; SKI390; WIN64652; MK-0683; SAHA, Suberoylanilide hydroxamic acid; SW-064652; Zolinza (TN); Vorinostat (JAN/USAN); N1-hydroxy-N8-phenyloctanediamide; Zolinza, MK-0683, SAHA; N'-hydroxy-N-phenyloctanediamide; N-Hydroxy-N'-phenyl octanediamide; N-Hyrdroxy-N'-phenyloctanediamide; N-hydroxy-N'-phenyloctanediamide; N-hydroxy-N'-phenyl-octane-1,8-diotic acid diamide; Vorinostat (HDAC inhibitor)
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Indication
In total 1 Indication(s)
Mycosis fungoides [ICD-11: 2B01]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Cutaneous T-cell lymphoma [ICD-11: 2B00]
[2]
Brain cancer [ICD-11: 2A00]
[3]
Target Histone deacetylase 1 (HDAC1) HDAC1_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C14H20N2O3
IsoSMILES
C1=CC=C(C=C1)NC(=O)CCCCCCC(=O)NO
InChI
1S/C14H20N2O3/c17-13(15-12-8-4-3-5-9-12)10-6-1-2-7-11-14(18)16-19/h3-5,8-9,19H,1-2,6-7,10-11H2,(H,15,17)(H,16,18)
InChIKey
WAEXFXRVDQXREF-UHFFFAOYSA-N
PubChem CID
5311
ChEBI ID
CHEBI:45716
TTD Drug ID
D0E7PQ
VARIDT ID
DR00769
INTEDE ID
DR1710
DrugBank ID
DB02546
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  MRAP: Metabolic Reprogramming via Altered Pathways
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
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Brain cancer [ICD-11: 2A00]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: Mechanistic target of rapamycin complex 1 (mTORC1) [3]
Metabolic Type Glucose metabolism
Resistant Disease Neuroblastoma [ICD-11: 2AOO.11]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vivo Model The nude, athymic female mice, with IMR-32 or SK-N-DZ cells Mice
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Tumor volume assay
Mechanism Description Besides both a block of glycolysis and OXPHOS, the HDAC/mTORC1 inhibitor combination produced significantly higher levels of reactive oxygen species (ROS) in the treated cells and in xenograft tumor samples, also a consequence of increased glycolytic block. The lead compounds were also tested for changes in the message levels of the glycolytic enzymes and their pathway activity, and HK2 and GPI glycolytic enzymes were most affected at their RNA message level.
Cutaneous T-cell lymphoma [ICD-11: 2B00]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interleukin-2 receptor subunit alpha (IL-2Ralpha) [2]
Resistant Disease Cutaneous T-cell lymphomas [ICD-11: 2B00.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation JAK-STAT signaling pathway Activation hsa04630
AKT/mTOR signaling pathway Regulation N.A.
MAPK signaling pathway Activation hsa04010
In Vitro Model H9SR cells embryonic stem cell Homo sapiens (Human) N.A.
HHSR cells embryonic stem cell Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot assay; Immunohistochemistry
Experiment for
Drug Resistance		 Flow cytometric assay
Mechanism Description Our findings highlight that attenuated ROS accelerates IL-2R translation and therefore brings about aberrant expression of IL-2R protein, leading to overactivation of JAK/STAT, AKT/mTOR and MAPK signaling events, which explains SAHA resistance to CTCL cells. Moreover, cantharidin could overcome SAHA resistance to CTCL by blocking IL-2R-related signaling via ROS dependent manner.
Pleural mesothelioma [ICD-11: 2C26]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-379 [1]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
Key Molecule: hsa-mir-411 [1]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interleukin-18 (IL18) [1]
Sensitive Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
ACC-MESO1 cells Lung Homo sapiens (Human) CVCL_5113
ACC-MESO4 cells Lung Homo sapiens (Human) CVCL_5114
NCI-H2052 cells Lung Homo sapiens (Human) CVCL_1518
NCI-H2452 cells Lung Homo sapiens (Human) CVCL_1553
NCI-H28 cells Lung Homo sapiens (Human) CVCL_1555
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-379 and miR-411 play a key role in the carcinogenesis of MPM cells by targeting IL-18 and contributing to the sensitivity of MPM cells to SAHA and PEM.
References
Ref 1 MiR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma. Oncol Rep. 2014 Dec;32(6):2365-72. doi: 10.3892/or.2014.3481. Epub 2014 Sep 16.
Ref 2 Cantharidin overcomes IL-2Ralpha signaling-mediated vorinostat resistance in cutaneous T-cell lymphoma through reactive oxygen species. J Immunother Cancer. 2024 Jul 14;12(7):e009099.
Ref 3 Reversing the HDAC-inhibitor mediated metabolic escape in MYCN-amplified neuroblastoma. Biomed Pharmacother. 2022 Jun;150:113032.

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