Drug Information

Drug (ID: DG00434) and It's Reported Resistant Information

• Name: Decitabine
• Synonyms: AzadC; Dacogen; Dezocitidine; NCGC_5ADOC; Dacogen (TN); E-7373; Decitabine (USAN/INN); Dacogen, 5-aza-2'-deoxycytidine,NSC 127716, Dacogen, DAC, Decitabine; 2'-Deoxy-5-azacytidine; 4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one; 4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-s-triazin-2(1H)-one; 4-Amino-1-(2-deoxy-beta-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one; 4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one; 5-AZAdC; 5-Aza-2′-Deoxycytidine; 5-Aza-2'-deoxycytidine; 5-Azadeoxycytidine; 5-Deoxy-2′-azacytidine; 5-aza-2-deoxycytidine; 5-aza-CdR; 5-aza-dC; 5A2dc
• Indication:
  In total 1 Indication(s)
  Myelodysplastic syndrome [ICD-11: 2A37]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Myelodysplastic syndrome [ICD-11: 2A37]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Osteosarcoma [ICD-11: 2B51]; [1]
• Target: Human Deoxyribonucleic acid (hDNA); NOUNIPROTAC; [1]
• Formula: C8H12N4O4
• IsoSMILES: C1[C@@H]([C@H](O[C@H]1N2C=NC(=NC2=O)N)CO)O
• InChI: 1S/C8H12N4O4/c9-7-10-3-12(8(15)11-7)6-1-4(14)5(2-13)16-6/h3-6,13-14H,1-2H2,(H2,9,11,15)/t4-,5+,6+/m0/s1
• InChIKey: XAUDJQYHKZQPEU-KVQBGUIXSA-N
• PubChem CID: 451668
• ChEBI ID: CHEBI:50131
• TTD Drug ID: D0X5XU
• INTEDE ID: DR1763
• DrugBank ID: DB01262

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

Osteosarcoma [ICD-11: 2B51]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Cyclin-dependent kinase inhibitor 2A (CDKN2A) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: HOTAIR-miR126-DNMT1-CDkN2A axis; Regulation; hsa05206
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HOS cells; Bone; Homo sapiens (Human); CVCL_0312
• In Vitro Model: 143B cells; Bone; Homo sapiens (Human); CVCL_2270
• In Vitro Model: NHOst cells; Bone; Homo sapiens (Human); N.A.
• In Vitro Model: HFob 1.19; Bone; Homo sapiens (Human); CVCL_3708
• Experiment for Molecule Alteration: RT-qPCR; ChIP assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: HOTAIR represses the expression of CDkN2A through inhibiting the promoter activity of CDkN2A by RNA hypermethylation. HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDkN2A axis.

Key Molecule: HOX transcript antisense RNA (HOTAIR) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: HOTAIR-miR126-DNMT1-CDkN2A axis; Regulation; hsa05206
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HOS cells; Bone; Homo sapiens (Human); CVCL_0312
• In Vitro Model: 143B cells; Bone; Homo sapiens (Human); CVCL_2270
• In Vitro Model: NHOst cells; Bone; Homo sapiens (Human); N.A.
• In Vitro Model: HFob 1.19; Bone; Homo sapiens (Human); CVCL_3708
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: HOTAIR represses the expression of CDkN2A through inhibiting the promoter activity of CDkN2A by RNA hypermethylation. HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDkN2A axis.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: DNA (cytosine-5)-methyltransferase 1 (DNMT1) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: HOTAIR-miR126-DNMT1-CDkN2A axis; Regulation; hsa05206
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HOS cells; Bone; Homo sapiens (Human); CVCL_0312
• In Vitro Model: 143B cells; Bone; Homo sapiens (Human); CVCL_2270
• In Vitro Model: NHOst cells; Bone; Homo sapiens (Human); N.A.
• In Vitro Model: HFob 1.19; Bone; Homo sapiens (Human); CVCL_3708
• Experiment for Molecule Alteration: RT-qPCR; Western blot analysis; ChIP assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: HOTAIR activates the expression of DNMT1 through repressing miR126, which is the negative regulator of DNMT1. HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDkN2A axis.

References

• Ref 1: A novel interplay between HOTAIR and DNA methylation in osteosarcoma cells indicates a new therapeutic strategy. J Cancer Res Clin Oncol. 2017 Nov;143(11):2189-2200. doi: 10.1007/s00432-017-2478-3. Epub 2017 Jul 20.
• Ref 2: Different mechanisms of drug resistance to hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukemiaDrug Resist Updat. 2022 Mar;61:100805. doi: 10.1016/j.drup.2022.100805. Epub 2022 Jan 21.