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]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [4]
• 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

  MRAP: Metabolic Reprogramming via Altered Pathways

  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 Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Glutamate dehydrogenase 1 (GLUD1) [4]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Sup-PR cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

Key Molecule: Glutamate dehydrogenase 2 (GLUD2) [4]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SEM-K2 cells; Blood; Homo sapiens (Human); CVCL_S906
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

Key Molecule: Alanine-serine-cysteine transporter 2 (ASCT2) [4]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Sup-B15 cells; Bone marrow; Homo sapiens (Human); CVCL_0103
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

Key Molecule: Alanine-serine-cysteine transporter 3 (ASCT3) [4]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Childhood acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SEM cells; Blood; Homo sapiens (Human); CVCL_0095
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell proliferation assay; Cell apoptosis assay
• Mechanism Description: In an attempt to explore the potential therapeutic effect of inhibiting one of the hits from our analysis, we targeted the glutamine-glutamate-alpha-ketoglutarate axis by three different strategies, all of which impaired mitochondrial respiration and ATP production and induced apoptosis. Thereby, we report that prednisolone resistance may be accompanied by considerable rewiring of transcriptional and biosynthesis programs.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-335 [1]

• Sensitive Disease: Paediatric acute lymphocytic leukemia [ICD-11: 2B33.4]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: MAPK signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: NF-kappaB signaling pathway; Regulation; N.A.
• 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]

• Sensitive Disease: Paediatric acute lymphocytic leukemia [ICD-11: 2B33.4]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: MAPK signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: NF-kappaB signaling pathway; Regulation; N.A.
• 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 blot 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]

• Resistant Disease: Nephrotic syndrome [ICD-11: GB41.0]
• Molecule Alteration: SNP; c.G2677T/A
• 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]

• Resistant Disease: Nephrotic syndrome [ICD-11: GB41.0]
• Molecule Alteration: SNP; c.G2677T/A
• 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
• Ref 4: Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Childhood Acute Lymphoblastic Leukaemia Cells. Int J Mol Sci. 2023 Feb 8;24(4):3378.