Drug Information

Drug (ID: DG00015) and It's Reported Resistant Information

• Name: Teniposide
• Synonyms: PTG; Teniposido; Teniposidum; Vehem; Vumon; Demethyl Epipodophyllotoxin Thenylidine Glucoside; VM 26; Teniposido [INN-Spanish]; Teniposidum [INN-Latin]; VM-26; Vee M-26; Veham-Sandoz; Vumon (TN); Teniposide (USAN/INN); Teniposide [USAN:BAN:INN]; VM-26 (TN); Vumon, VM-26, Vehem, NSC 122819, Teniposide; Epipodophyllotoxin, 4'-demethyl-, 9-(4,6-O-2-thenylidene-beta-D-glucopyranoside); 4'-Demethyl-epipodophyllotoxin-beta-D-thenylidene-glucoside; 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-2-thenylidene-beta-D-glucopyranoside); 4'-Demethylepipodophyllotoxin 9-(4,6-O-2-thenylidene-beta-D-glucopyranoside); 4'-Demethylepipodophyllotoxin thenylidene glucoside; 4'-Demethylepipodophyllotoxin-beta-D-thenylidine glucoside; 4'-Dimethyl-9-(4,6-O-2-thenyid)-epipodophyllotoxin; 4-Demethylepipodophyllotoxin-.beta.-D-thenylideneglucoside
• Indication:
  In total 1 Indication(s)
  Mature B-cell lymphoma [ICD-11: 2A85]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Brain cancer [ICD-11: 2A00]; [2]
• Target: DNA topoisomerase II (TOP2); TOP2A_HUMAN TOP2B_HUMAN; [1]
• Formula: C32H32O13S
• IsoSMILES: COC1=CC(=CC(=C1O)OC)[C@H]2[C@@H]3[C@H](COC3=O)[C@@H](C4=CC5=C(C=C24)OCO5)O[C@H]6[C@@H]([C@H]([C@H]7[C@H](O6)CO[C@H](O7)C8=CC=CS8)O)O
• InChI: 1S/C32H32O13S/c1-37-19-6-13(7-20(38-2)25(19)33)23-14-8-17-18(42-12-41-17)9-15(14)28(16-10-39-30(36)24(16)23)44-32-27(35)26(34)29-21(43-32)11-40-31(45-29)22-4-3-5-46-22/h3-9,16,21,23-24,26-29,31-35H,10-12H2,1-2H3/t16-,21+,23+,24-,26+,27+,28+,29+,31+,32-/m0/s1
• InChIKey: NRUKOCRGYNPUPR-QBPJDGROSA-N
• PubChem CID: 452548
• TTD Drug ID: D01DBQ
• VARIDT ID: DR00021
• INTEDE ID: DR1550
• DrugBank ID: DB00444

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

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-21 [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: U373 MG cells; Brain; Homo sapiens (Human); CVCL_2219
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 likely contributes to VM-26 resistance through depression of the expression of LRRFIP1, leading to the reduction of the cytotoxicity of chemotherapy drugs through activation of the NF-kB pathway.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Leucine-rich repeat flightless-interacting protein 1 (LRRFIP1) [2]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: U373 MG cells; Brain; Homo sapiens (Human); CVCL_2219
• Experiment for Molecule Alteration: Fluorescent reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 likely contributes to VM-26 resistance through depression of the expression of LRRFIP1, leading to the reduction of the cytotoxicity of chemotherapy drugs through activation of the NF-kB pathway.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-181 [1]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3'-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: E3 ubiquitin-protein ligase Mdm2 (MDM2) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3'-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b.

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-20a [3]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Colorectal adenocarcinoma [ICD-11: 2B91.2]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-20a overexpression resulted in resistance to these chemotherapy agents, while miR-20a knockdown led to sensitization, miR-20a down-regulated both BNIP2 mRNA and BNIP2 protein levels. miR-20a down-regulated the expression of the proapoptotic factor BNIP2, leading to an imbalance of anti-apoptosis and pro-apoptosis factors, resulting in the blockage of events leading to apoptosis.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 2 (BNIP2) [3]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Colorectal adenocarcinoma [ICD-11: 2B91.2]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-20a overexpression resulted in resistance to these chemotherapy agents, while miR-20a knockdown led to sensitization, miR-20a down-regulated both BNIP2 mRNA and BNIP2 protein levels. miR-20a down-regulated the expression of the proapoptotic factor BNIP2, leading to an imbalance of anti-apoptosis and pro-apoptosis factors, resulting in the blockage of events leading to apoptosis.

References

• Ref 1: MiR-181b sensitizes glioma cells to teniposide by targeting MDM2. BMC Cancer. 2014 Aug 25;14:611. doi: 10.1186/1471-2407-14-611.
• Ref 2: MicroRNA-21 targets LRRFIP1 and contributes to VM-26 resistance in glioblastoma multiforme. Brain Res. 2009 Aug 25;1286:13-8. doi: 10.1016/j.brainres.2009.06.053. Epub 2009 Jun 24.
• Ref 3: miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines. Acta Biochim Biophys Sin (Shanghai). 2011 Mar;43(3):217-25. doi: 10.1093/abbs/gmq125. Epub 2011 Jan 17.