Drug Information

Drug (ID: DG00199) and It's Reported Resistant Information

• Name: Prednisone
• Synonyms: Adasone; Ancortone; Bicortone; Cartancyl; Colisone; Cortan; Cortidelt; Cotone; Dacorten; Dacortin; Decortancyl; Decortin; Decortisyl; Dehydrocortisone; Dekortin; Dellacort; Deltacortene; Deltacortisone; Deltacortone; Deltasone; Deltison; Deltisona; Deltisone; Deltra; Diadreson; Econosone; Encorton; Encortone; Enkortolon; Enkorton; Fiasone; Hostacortin; Incocortyl; Juvason; Kortancyl; Lisacort; Lodotra; Metacortandracin; Meticorten; Nisona; Nizon; Novoprednisone; Nurison; Orasone; Panafcort; Panasol; Paracort; Parmenison; Pehacort; Precort; Predeltin; Prednicorm; Prednicort; Prednicot; Prednidib; Prednilonga; Prednison; Prednisona; Prednisonum; Prednitone; Prednizon; Prednovister; Presone; Pronison; Pronisone; Rectodelt; Retrocortine; Servisone; Sone; Sterapred; Supercortil; Ultracorten; Ultracortene; Winpred; Wojtab; Zenadrid; Dellacort A; Delta E; Delta cortelan; Liquid Pred; Origen Prednisone; Prednisone Intensol; Zenadrid [veterinary]; P1276; U 6020; Apo-Prednisone; Delta E.; Delta-Cortelan; Delta-Cortisone; Delta-Cortone; Delta-Dome; Delta-E; Delta1-Cortisone; Delta1-Dehydrocortisone; Di-Adreson; In-Sone; Me-Korti; Meticortelone (TN); Meticorten (TN); Meticorten (Veterinary); Metrevet (Veterinary); Prednicen-M; Prednisona [INN-Spanish]; Prednisone [INN:BAN]; Prednisonum [INN-Latin]; SK-Prednisone; Zenadrid (veterinary); Delta(sup 1)-Cortisone; Delta(sup 1)-Dehydrocortisone; Delta(sup1)-Cortisone; Delta-1-Cortisone; Delta-1-Dehydrocortisone; Deltasone, Liquid Pred, Orasone, Adasone, Deltacortisone,Prednisone; (1S,2R,10S,11S,14R,15S)-14-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-5,17-dione; (8S,9S,10R,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,9,12,14,15,16-octahydrocyclopenta[a]phenanthrene-3,11-dione; (8xi,9xi,14xi)-17,21-dihydroxypregna-1,4-diene-3,11,20-trione; 1,2-Dehydrocortisone; 1,4-Pregnadiene-17-alpha,21-diol-3,11,20-trione; 1,4-Pregnadiene-17.alpha.,21-diol-3,11,20-trione; 1,4-Pregnadiene-17alpha,21-diol-3,11,20-trione; 1-Cortisone; 1-Dehydrocortisone; 17,21-Dihydroxypregna-1,4-diene-3,11,20-trione; 17alpha,21-Dihydroxy-1,4-pregnadiene-3,11,20-trione
• Indication:
  In total 3 Indication(s)
  Postoperative inflammation [ICD-11: 1A00-CA43]; Approved; [1]
  Atopic eczema [ICD-11: EA80]; Phase 1; [1]
  Eczema [ICD-11: EA80-EA89]; Phase 1; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (5 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [2]
  Diffuse large B-cell lymphoma [ICD-11: 2A81]; [3]
  Myasthenia gravis [ICD-11: 8C60]; [4]
  Rheumatoid arthritis [ICD-11: FA20]; [5]
  Thrombocytopenia [ICD-11: 3B64]; [6]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [1]
• Target: Glucocorticoid receptor (NR3C1); GCR_HUMAN; [1]
• Formula: C21H26O5
• IsoSMILES: C[C@]12CC(=O)[C@H]3[C@H]([C@@H]1CC[C@@]2(C(=O)CO)O)CCC4=CC(=O)C=C[C@]34C
• InChI: 1S/C21H26O5/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/h5,7,9,14-15,18,22,26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,18+,19-,20-,21-/m0/s1
• InChIKey: XOFYZVNMUHMLCC-ZPOLXVRWSA-N
• PubChem CID: 5865
• ChEBI ID: CHEBI:8382
• TTD Drug ID: D0IL7L
• VARIDT ID: DR00438
• INTEDE ID: DR1334
• DrugBank ID: DB00635

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Diffuse large B-cell lymphoma [ICD-11: 2A81]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-148b [3]

• Molecule Alteration: Acetylation; Down-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: HDAC6/miR148b/Ezrin signaling pathway; Regulation; hsa05206
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vitro Model: CRL2631/CHOP cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-miR-125b-5p [7]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SU-DHL-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_9550
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Expression levels of exosomal miR-99a-5p/miR-125b-5p & their correlation with clinicopathological features in DLBCL patients, the expression levels of miR-99a-5p and miR-125b-5p were significantly higher in the chemoresistant group than in the chemosensitive group.

Key Molecule: hsa-miR-99a-5p [7]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SU-DHL-2 cells; Pleural effusion; Homo sapiens (Human); CVCL_9550
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Expression levels of exosomal miR-99a-5p/miR-125b-5p & their correlation with clinicopathological features in DLBCL patients, the expression levels of miR-99a-5p and miR-125b-5p were significantly higher in the chemoresistant group than in the chemosensitive group.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ezrin (EZR) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: HDAC6/miR148b/Ezrin signaling pathway; Regulation; hsa05206
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vitro Model: CRL2631/CHOP cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The high level of HDAC6 inhibited miR-148b via maintaining the low acetylation of histones H3 and H4 in the miR-148b promoter, thus rescuing Ezrin expression and promoting CHOP resistance in DLBCL.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-21 [8]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 impacts the PI3k/AkT signaling pathway through the regulation of PTEN, thereby affecting cellular sensitivity to the CHOP chemotherapeutic regimen.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatase and tensin homolog (PTEN) [8]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: CRL2631 cells; Bone marrow; Homo sapiens (Human); CVCL_3611
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 impacts the PI3k/AkT signaling pathway through the regulation of PTEN, thereby affecting cellular sensitivity to the CHOP chemotherapeutic regimen.

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA mismatch repair protein Msh6 (MSH6) [2]

• Molecule Alteration: Structural variation; Copy number loss
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Peripheral blood; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: Bone marrow; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Somatic copy number alteration assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Finally, relapse-specific focal deletion of MSH6 and, consequently, reduced gene expression were found in 2 of 20 cases. In an independent cohort of children with ALL, reduced expression of MSH6 was associated with resistance to mercaptopurine and prednisone, thereby providing a plausible mechanism by which this acquired deletion contributes to drug resistance at relapse.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOXA cluster antisense RNA 2 (HOXA-AS2) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGFR/RAS/RAF/MEK/ERK signaling pathway; Activation; hsa01521
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEk/ERk pathway.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Homeobox protein Hox-A3 (HOXA3) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGFR/RAS/RAF/MEK/ERK signaling pathway; Activation; hsa01521
• In Vitro Model: Jurkat cells; Pleural effusion; Homo sapiens (Human); CVCL_0065
• In Vitro Model: CCRF-CEM cells; Pleural effusion; Homo sapiens (Human); CVCL_0207
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEk/ERk pathway.

ICD-03: Blood/blood-forming organs diseases

Thrombocytopenia [ICD-11: 3B64]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [6]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Primary immune thrombocytopenia [ICD-11: 3B64.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: B-cells; Peripheral blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Rhodamine 123 efflux assay
• Mechanism Description: The functional activity and mRNA level of P-gp were significantly higher in glucocorticoids-nonresponsive patients than in glucocorticoids-responsive patients with primary immune thrombocytopenia.

ICD-08: Nervous system diseases

Myasthenia gravis [ICD-11: 8C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Myasthenia gravis [ICD-11: 8C60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lymphocyte; Lymph node; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Prednisone (PDN) is transported by P-glycoprotein (P-gp). P-gp overfunction has been associated with resistance to several drug.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Myasthenia gravis [ICD-11: 8C60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lymphocyte; Lymph node; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Prednisone (PDN) is transported by P-glycoprotein (P-gp). P-gp overfunction has been associated with resistance to several drug.

ICD-15: Musculoskeletal/connective-tissue diseases

Rheumatoid arthritis [ICD-11: FA20]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [5]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

References

• Ref 1: TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEK/ERK pathway. Biomed Pharmacother. 2019 Jan;109:1640-1649. doi: 10.1016/j.biopha.2018.10.046. Epub 2018 Nov 16.
• Ref 2: Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia. Blood. 2008 Nov 15;112(10):4178-83. doi: 10.1182/blood-2008-06-165027. Epub 2008 Sep 2.
• Ref 3: Down-regulated miR-148b increases resistance to CHOP in diffuse large B-cell lymphoma cells by rescuing Ezrin. Biomed Pharmacother. 2018 Oct;106:267-274. doi: 10.1016/j.biopha.2018.06.093. Epub 2018 Jun 28.
• Ref 4: Multidrug resistance-1 (MDR-1) in autoimmune disorders IV. P-glycoprotein overfunction in lymphocytes from myasthenia gravis patients .Biomed Pharmacother. 2004 Jun;58(5):320-4. doi: 10.1016/j.biopha.2004.04.008. 10.1016/j.biopha.2004.04.008
• Ref 5: Drug-resistance in rheumatoid arthritis: the role of p53 gene mutations, ABC family transporters and personal factors .Curr Opin Pharmacol. 2020 Oct;54:59-71. doi: 10.1016/j.coph.2020.08.002. Epub 2020 Sep 14. 10.1016/j.coph.2020.08.002
• Ref 6: Effects of the multidrug resistance-1 gene on drug resistance in primary immune thrombocytopenia .Autoimmunity. 2016 Nov;49(7):486-495. doi: 10.1080/08916934.2016.1191476. Epub 2016 Jun 3. 10.1080/08916934.2016.1191476
• Ref 7: Exosome-derived miRNAs as predictive biomarkers for diffuse large B-cell lymphoma chemotherapy resistance. Epigenomics. 2019 Jan;11(1):35-51. doi: 10.2217/epi-2018-0123. Epub 2018 Sep 13.
• Ref 8: MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen. Int J Hematol. 2013 Feb;97(2):223-31. doi: 10.1007/s12185-012-1256-x. Epub 2012 Dec 30.