Disease Information

General Information of the Disease (ID: DIS00344)

• Name: Chronic kidney disease
• ICD: ICD-11: GB61

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Canagliflozin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Solute carrier family 5 member 2 (SLC5A2) [1]

• Sensitive Disease: Chronic kidney disease [ICD-11: GB61.0]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Canagliflozin
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Treatment with the SGLT2 (sodium-glucose cotransporter 2) inhibitor canagliflozin results in early and sustained reductions in systolic blood pressure in people with type 2 diabetes and chronic kidney disease, regardless of baseline blood pressure, number of blood pressure lowering agents, and history of apparent treatment-resistant hypertension.

Streptozocin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Growth arrest specific 5 (GAS5) [2]

• Resistant Disease: Chronic kidney disease [ICD-11: GB61.0]
• Molecule Alteration: Down-regulation; Interaction
• Resistant Drug: Streptozocin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Renal tubular epithelial cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Overexpression assay; RIP experiments assay; RNA pull down assay; ChIP assay
• Mechanism Description: Long noncoding RNA growth arrest-specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2.

Investigative Drug(s) 1 drug(s) in total

Germacrone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa_circRNA_0000309 [3]

• Resistant Disease: Diabetic nephropathy [ICD-11: GB61.Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Germacrone
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: MPC5 cells; Kidney; Mus musculus (Mouse); CVCL_AS87
• In Vivo Model: C57BL/6J mouse model; C57BL/KsJ mouse model; db/db mice mouse model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Mmu_circRNA_0000309 silence mediates drug resistance to germacrone in DN mice. mmu_circRNA_0000309 sponges miR-188-3p, and subsequently upregulates GPX4 expression, inactivating ferroptosis-dependent mitochondrial function and podocyte apoptosis.

Key Molecule: hsa_circRNA_0000309 [3]

• Resistant Disease: Diabetic nephropathy [ICD-11: GB61.Z]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Germacrone
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: MPC5 cells; Kidney; Mus musculus (Mouse); CVCL_AS87
• In Vivo Model: C57BL/6J mouse model; C57BL/KsJ mouse model; db/db mice mouse model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Mmu_circRNA_0000309 silence mediates drug resistance to germacrone in DN mice. mmu_circRNA_0000309 sponges miR-188-3p, and subsequently upregulates GPX4 expression, inactivating ferroptosis-dependent mitochondrial function and podocyte apoptosis.

References

• Ref 1: Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial .Circulation. 2021 May 4;143(18):1735-1749. doi: 10.1161/CIRCULATIONAHA.120.048740. Epub 2021 Feb 8. 10.1161/CIRCULATIONAHA.120.048740
• Ref 2: Long noncoding RNA growth arrest-specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2FASEB J. 2020 Feb;34(2):2703-2714. doi: 10.1096/fj.201901380RR. Epub 2020 Jan 9.
• Ref 3: A Novel Identified Circular RNA, mmu_mmu_circRNA_0000309, Involves in Germacrone-Mediated Improvement of Diabetic Nephropathy Through Regulating Ferroptosis by Targeting miR-188-3p/GPX4 Signaling Axis .Antioxid Redox Signal. 2022 Apr;36(10-12):740-759. doi: 10.1089/ars.2021.0063. 10.1089/ars.2021.0063