Drug Information

Drug (ID: DG00164) and It's Reported Resistant Information

• Name: Prednisolone
• Synonyms: Nanocort; Prednisolone (injectable liposome formulation, rheumatoid arthritis); Prednisolone (injectable liposome formulation, rheumatoid arthritis), Enceladus; Prednisolone (injectable liposome formulation, rheumatoid arthritis), Galapagos
• Indication:
  In total 2 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
  Multiple sclerosis [ICD-11: 8A40]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Hodgkin lymphoma [ICD-11: 2B30]; [2]
  Nephrotic syndrome [ICD-11: GB41]; [3]
• Target: Glucocorticoid receptor (NR3C1); GCR_HUMAN; [1]
• Formula: C21H28O5
• IsoSMILES: C[C@]12C[C@@H]([C@H]3[C@H]([C@@H]1CC[C@@]2(C(=O)CO)O)CCC4=CC(=O)C=C[C@]34C)O
• InChI: 1S/C21H28O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h5,7,9,14-16,18,22,24,26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1
• InChIKey: OIGNJSKKLXVSLS-VWUMJDOOSA-N
• PubChem CID: 5755
• ChEBI ID: CHEBI:8378
• TTD Drug ID: D0D1SG
• VARIDT ID: DR00428
• INTEDE ID: DR1332
• DrugBank ID: DB00860

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-335 [1]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Paediatric acute lymphocytic leukemia [ICD-11: 2B33.4]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: MAPK signaling pathway; Regulation; hsa04010
• Cell Pathway Regulation: NF-kappaB signaling pathway; Regulation; hsa04064
• In Vitro Model: MLL/AF4+ RS4 cells; Blood; Homo sapiens (Human); CVCL_0093
• In Vitro Model: 697 cells; Bone marrow; Homo sapiens (Human); CVCL_0079
• In Vitro Model: Sup-B15 cells; Bone marrow; Homo sapiens (Human); CVCL_0103
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MAPk1 is a novel target of MIR335, and that MEk/ERk inhibitor treatment enhanced prednisolone-induced cell death through the activation of BIM (BCL2L11).

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mitogen-activated protein kinase 1 (MAPK1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Paediatric acute lymphocytic leukemia [ICD-11: 2B33.4]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: MAPK signaling pathway; Regulation; hsa04010
• Cell Pathway Regulation: NF-kappaB signaling pathway; Regulation; hsa04064
• In Vitro Model: MLL/AF4+ RS4 cells; Blood; Homo sapiens (Human); CVCL_0093
• In Vitro Model: 697 cells; Bone marrow; Homo sapiens (Human); CVCL_0079
• In Vitro Model: Sup-B15 cells; Bone marrow; Homo sapiens (Human); CVCL_0103
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MAPk1 is a novel target of MIR335, and that MEk/ERk inhibitor treatment enhanced prednisolone-induced cell death through the activation of BIM (BCL2L11).

ICD-16: Genitourinary system diseases

Nephrotic syndrome [ICD-11: GB41]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [3]

• Molecule Alteration: SNP; c.G2677T/A
• Resistant Disease: Nephrotic syndrome [ICD-11: GB41.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood sample; N.A.
• Experiment for Molecule Alteration: PCR-RFLP
• Mechanism Description: MDR1 G2677T/A polymorphism was significantly associated with steroid resistance.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [3]

• Molecule Alteration: SNP; c.G2677T/A
• Resistant Disease: Nephrotic syndrome [ICD-11: GB41.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood sample; N.A.
• Experiment for Molecule Alteration: PCR-RFLP
• Mechanism Description: MDR1 G2677T/A polymorphism was significantly associated with steroid resistance.

References

• Ref 1: Deregulated MIR335 that targets MAPK1 is implicated in poor outcome of paediatric acute lymphoblastic leukaemia. Br J Haematol. 2013 Oct;163(1):93-103. doi: 10.1111/bjh.12489. Epub 2013 Jul 25.
• Ref 2: Non-Hodgkin's B-cell lymphoma: advances in molecular strategies targeting drug resistance .Exp Biol Med (Maywood). 2013 Sep;238(9):971-90. doi: 10.1177/1535370213498985. Epub 2013 Aug 28. 10.1177/1535370213498985
• Ref 3: Multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: impact on susceptibility and response to steroids .Gene. 2013 Nov 10;530(2):201-7. doi: 10.1016/j.gene.2013.08.045. Epub 2013 Aug 27. 10.1016/j.gene.2013.08.045