Drug (ID: DG00017) and It's Reported Resistant Information
Name
Vinorelbine
Synonyms
Eunades; Exelbine; NVB; Navelbine; Vinorelbin; Vinorelbina; Vinorelbinum; Navelbine base; Vinorelbina [Spanish]; Vinorelbine Ditartarate; Vinorelbine ditartrate; Vinorelbine tartrate; Vinorelbinum [Latin]; KW 2307; KW 2307 base; ANX-530; KW-2307; Navelbine (TN); SDP-012; Vinorelbine (INN); Vinorelbine [INN:BAN]; Aspidospermidine-3-carboxylic acid; Nor-5'-anhydrovinblastine; Methyl (2beta,3beta,4beta,5alpha,12beta,19alpha)-4-acetoxy-15-[(6R,8S)-4-ethyl-8-(methoxycarbonyl)-1,3,6,7,8,9-hexahydro-2,6-methanoazecino[4,3-b]indol-8-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate; Methyl (2b,3b,4b,5a,12b,19a)-4-(acetyloxy)-15-[(6R,8S)-4-ethyl-8-(methoxycarbonyl)-1,3,6,7,8,9-hexahydro-2,6-methanoazecino[4,3-b]indol-8-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate
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Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Pleural mesothelioma [ICD-11: 2C26]
[2]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Esophageal cancer [ICD-11: 2B70]
[1]
Target Tubulin (TUB) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C45H54N4O8
IsoSMILES
CCC1=C[C@H]2C[C@@](C3=C(CN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)[C@]78CCN9[C@H]7[C@@](C=CC9)([C@H]([C@@]([C@@H]8N6C)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC
InChI
1S/C45H54N4O8/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45-/m0/s1
InChIKey
GBABOYUKABKIAF-IELIFDKJSA-N
PubChem CID
5311497
ChEBI ID
CHEBI:480999
TTD Drug ID
D01HTL
VARIDT ID
DR01343
DrugBank ID
DB00361
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Esophageal cancer [ICD-11: 2B70]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-193a-3p [1]
Molecule Alteration Expression
Up-regulation
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.
Key Molecule: hsa-miR-193a-3p [1]
Molecule Alteration Expression
Up-regulation
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. The regulation role of miR-193a-3p on multi-chemoresistance and radioresistance were mediated by PSEN1.
Key Molecule: hsa-miR-193a-3p [1]
Molecule Alteration Expression
Up-regulation
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. The regulation role of miR-193a-3p on multi-chemoresistance and radioresistance were mediated by PSEN1.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Presenilin-1 (PSEN1) [1]
Molecule Alteration Expression
Down-regulation
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.
Pleural mesothelioma [ICD-11: 2C26]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-15a [2]
Molecule Alteration Expression
Down-regulation
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-15a [2]
Molecule Alteration Expression
Down-regulation
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-16 [2]
Molecule Alteration Expression
Down-regulation
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: hsa-mir-16 [2]
Molecule Alteration Expression
Down-regulation
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: Forkhead box protein O3 (FOXO3) [2]
Molecule Alteration Expression
Down-regulation
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
Key Molecule: Forkhead box protein O3 (FOXO3) [2]
Molecule Alteration Expression
Down-regulation
Resistant Disease Malignant pleural mesothelioma [ICD-11: 2C26.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model MSTO-211H cells Lung Homo sapiens (Human) CVCL_1430
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
SYBR Green-based assay
Mechanism Description Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only.
References
Ref 1 miR-193a-3p regulation of chemoradiation resistance in oesophageal cancer cells via the PSEN1 gene. Gene. 2016 Apr 1;579(2):139-45. doi: 10.1016/j.gene.2015.12.060. Epub 2015 Dec 29.
Ref 2 Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways .Cancer Drug Resist. 2019 Dec 19;2(4):1193-1206. doi: 10.20517/cdr.2019.41. eCollection 2019. 10.20517/cdr.2019.41

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