Drug Information

Drug (ID: DG00337) and It's Reported Resistant Information
Name
Pirarubicin
Synonyms
Pinorubicin (TN); Therarubucin (TN)
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Indication
In total 1 Indication(s)
Breast cancer [ICD-11: 2C60]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (3 diseases)
Bladder cancer [ICD-11: 2C94]
[2]
Breast cancer [ICD-11: 2C60]
[3]
Liver cancer [ICD-11: 2C12]
[4]
Target Human Deoxyribonucleic acid (hDNA) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C32H37NO12
IsoSMILES
C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)O[C@H]6CCCCO6
InChI
1S/C32H37NO12/c1-14-31(45-21-8-3-4-9-42-21)17(33)10-22(43-14)44-19-12-32(40,20(35)13-34)11-16-24(19)30(39)26-25(28(16)37)27(36)15-6-5-7-18(41-2)23(15)29(26)38/h5-7,14,17,19,21-22,31,34,37,39-40H,3-4,8-13,33H2,1-2H3/t14-,17-,19-,21-,22-,31+,32-/m0/s1
InChIKey
KMSKQZKKOZQFFG-HSUXVGOQSA-N
PubChem CID
636397
ChEBI ID
CHEBI:32011
TTD Drug ID
D0T8EH
VARIDT ID
DR01430
DrugBank ID
DB11616
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
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Liver cancer [ICD-11: 2C12]
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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: Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) [4]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
L02 cells Liver Homo sapiens (Human) CVCL_6926
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells. HULC inhibits the expression and activity of miR6825-5p, miR6845-5p and miR6886-3p.
Key Molecule: hsa-miR-6825-5p [4]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
L02 cells Liver Homo sapiens (Human) CVCL_6926
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR6825-5p, miR6845-5p and miR6886-3p could decrease the level of USP22 protein by binding to the 3'-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. The pathway 'HULC/USP22/Sirt1/ protective autophagy' attenuates the sensitivity of HCC cells to chemotherapeutic agents.
Key Molecule: hsa-miR-6845-5p [4]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
L02 cells Liver Homo sapiens (Human) CVCL_6926
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR6825-5p, miR6845-5p and miR6886-3p could decrease the level of USP22 protein by binding to the 3'-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. The pathway 'HULC/USP22/Sirt1/ protective autophagy' attenuates the sensitivity of HCC cells to chemotherapeutic agents.
Key Molecule: hsa-miR-6886-3p [4]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
L02 cells Liver Homo sapiens (Human) CVCL_6926
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR6825-5p, miR6845-5p and miR6886-3p could decrease the level of USP22 protein by binding to the 3'-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. The pathway 'HULC/USP22/Sirt1/ protective autophagy' attenuates the sensitivity of HCC cells to chemotherapeutic agents.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Ubiquitin carboxyl-terminal hydrolase 22 (USP22) [4]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
L02 cells Liver Homo sapiens (Human) CVCL_6926
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR6825-5p, miR6845-5p and miR6886-3p could decrease the level of USP22 protein by binding to the 3'-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. The pathway 'HULC/USP22/Sirt1/ protective autophagy' attenuates the sensitivity of HCC cells to chemotherapeutic agents.
Breast cancer [ICD-11: 2C60]
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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: H19, imprinted maternally expressed transcript (H19) [3]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cullin4A/MDR1 signaling pathway Regulation hsa05206
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Quantitative real-time RT-PCR
Experiment for
Drug Resistance		 CellTiter AQueous One Solution Cell Proliferation Assay
Mechanism Description LncRNA H19 is a major mediator of doxorubicin chemoresistance in breast cancer cells through a cullin4A-MDR1 pathway. H19 overexpression was contributed to cancer cell resistance to anthracyclines and paclitaxel as knockdown of H19 LncRNA by a specific H19 shRNA in Dox-resistant cells significantly improved the cell sensitivity to anthracyclines and paclitaxel.
Cervical cancer [ICD-11: 2C77]
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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-34c-5p [5]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Cervical cancer [ICD-11: 2C77.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
miR34C-5p/ATG4B-autophagy signaling pathway Regulation hsa05206
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
Siha cells Cervix uteri Homo sapiens (Human) CVCL_0032
C33A cells Uterus Homo sapiens (Human) CVCL_1094
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description On the one side, THP induces apoptosis, which results in cell death. On the other side, THP activates the MIR34C-5p-ATG4B-autophagy signaling axis via the sequential triggering of MIR34C-5p downregulation, ATG4B mRNA stability enhancement, and ATG4B upregulation and autophagy induction. Moreover, autophagy protects cervical cancer cells from cell death. The autophagy inhibitor CQ sensitizes cervical cancer cells to THP treatment.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cysteine protease ATG4B (ATG4B) [5]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Cervical cancer [ICD-11: 2C77.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
miR34C-5p/ATG4B-autophagy signaling pathway Regulation hsa05206
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
Siha cells Cervix uteri Homo sapiens (Human) CVCL_0032
C33A cells Uterus Homo sapiens (Human) CVCL_1094
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description On the one side, THP induces apoptosis, which results in cell death. On the other side, THP activates the MIR34C-5p-ATG4B-autophagy signaling axis via the sequential triggering of MIR34C-5p downregulation, ATG4B mRNA stability enhancement, and ATG4B upregulation and autophagy induction. Moreover, autophagy protects cervical cancer cells from cell death. The autophagy inhibitor CQ sensitizes cervical cancer cells to THP treatment.
Bladder cancer [ICD-11: 2C94]
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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-34b-3p [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
Notch/PkC/Ca++ signaling pathway Inhibition hsa04330
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
EJ cells Bladder Homo sapiens (Human) CVCL_UI82
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description miR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes.
Key Molecule: hsa-miR-22-3p [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
T24 cells Bladder Homo sapiens (Human) CVCL_0554
UM-UC-3 cells Bladder Homo sapiens (Human) CVCL_1783
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
HTB-1 cells Bladder Homo sapiens (Human) CVCL_0359
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: G1/S-specific cyclin-D2 (CCND2) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
Notch/PkC/Ca++ signaling pathway Inhibition hsa04330
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
EJ cells Bladder Homo sapiens (Human) CVCL_UI82
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description miR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes.
Key Molecule: P2Y purinoceptor 1 (P2RY1) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
Notch/PkC/Ca++ signaling pathway Inhibition hsa04330
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
EJ cells Bladder Homo sapiens (Human) CVCL_UI82
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description miR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes.
Key Molecule: Neuroepithelial cell-transforming gene 1 protein (NET1) [2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
T24 cells Bladder Homo sapiens (Human) CVCL_0554
UM-UC-3 cells Bladder Homo sapiens (Human) CVCL_1783
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
HTB-1 cells Bladder Homo sapiens (Human) CVCL_0359
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-193a-3p [6]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
DNA damage response signaling pathway Activation hsa04218
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Presenilin-1 (PSEN1) [6]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
DNA damage response signaling pathway Activation hsa04218
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
References
Ref 1 MiR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes. Med Sci Monit. 2019 Feb 19;25:1323-1335. doi: 10.12659/MSM.913746.
Ref 2 miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells. Oncol Rep. 2018 Jun;39(6):2731-2740. doi: 10.3892/or.2018.6355. Epub 2018 Apr 4.
Ref 3 LncRNA H19 is a major mediator of doxorubicin chemoresistance in breast cancer cells through a cullin4A-MDR1 pathway. Oncotarget. 2017 Sep 21;8(54):91990-92003. doi: 10.18632/oncotarget.21121. eCollection 2017 Nov 3.
Ref 4 LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells. Oncogene. 2017 Jun 22;36(25):3528-3540. doi: 10.1038/onc.2016.521. Epub 2017 Feb 6.
Ref 5 Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin. Autophagy. 2016 Jul 2;12(7):1105-17. doi: 10.1080/15548627.2016.1173798. Epub 2016 Apr 20.
Ref 6 The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer. Biochim Biophys Acta. 2015 Mar;1852(3):520-8. doi: 10.1016/j.bbadis.2014.12.014. Epub 2014 Dec 24.

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