Drug Information

Drug (ID: DG00751) and It's Reported Resistant Information

• Name: Idebenone
• Synonyms: Idebenone; 58186-27-9; Idebenona; Idebenonum; CV 2619; 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione; CV-2619; Sovrima; UNII-HB6PN45W4J; BRN 2001459; CHEBI:31687; 2-(10-Hydroxydecyl)-5,6-dimethoxy-3-methyl-1,4-benzoquinone; 6-(10-Hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone; HB6PN45W4J; Raxone; 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl-2,5-cyclohexadiene-1,4-dione; 5,6-DIMETHOXY-2-(10-HYDROXYDECYL)-3-METHYL-1,4-BENZOQUINONE; 2,5-Cyclohexadiene-1,4-dione, 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl-; MFCD00274552; NSC-759228; NCGC00160514-01; 2-(10-Hydroxydecyl)-5,6-dimethoxy-3-methyl-p-benzoquinone; 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methylbenzo-1,4-quinone; 2,5-Cyclohexadiene-1,4-dione, 5,6-dimethoxy-2-(10-hydroxydecyl)-3-methyl-; DSSTox_CID_20678; DSSTox_RID_79536; DSSTox_GSID_40678; Idebenonum [Latin]; Idebenona [Spanish]; hydroxydecyl ubiquinone; Idebenone [INN:JAN]; 2,3-dimethoxy-5-methyl-6-(10'-hydroxydecyl)-1,4-benzoquinone; 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methyl-1,4-benzoquinone; SMR000466364; CAS-58186-27-9; SR-01000759378; Cerestabon; Catena; Mnesis; Avan; Oristar hdu; Idebenone- Bio-X; Raxone (TN); SNT-MC17; SCHEMBL28320; Idebenone (JAN/USAN/INN); MLS000759487; MLS001032035; MLS001424002; MLS006011882; Idebenone, analytical standard; CHEMBL252556; QSA-10; DTXSID0040678; Idebenone, >=98% (HPLC); FR114; HMS2051O06; HMS2089D08; HMS3393O06; HMS3656K22; HMS3713A10; HMS3884B12; Pharmakon1600-01505755; ALBB-027258; BCP09116; HY-N0303; STR09227; ZINC1542890; Tox21_111864; BBL025842; BDBM50505498; NSC759228; s2605; STK801942; AKOS005622577; Tox21_111864_1; AC-4337; CCG-100846; KS-5193; MCULE-6391829243; NC00096; NSC 759228; SB19130; NCGC00160514-02; NCGC00160514-03; BI164565; SY051193; SBI-0207024.P001; DB-053168; FT-0617205; I0848; SW219495-1; D01750; H10427; J10031; AB00639997-04; AB00639997-06; AB00639997_07; AB00639997_08; 186I279; A-68500; Q4197874; SR-01000759378-4; SR-01000759378-5; SR-01000759378-6; BRD-K37516142-001-01-4; 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methylbenzoquinone; 2,3-Dimethoxy-6-(10-hydroxydecyl)-5-methyl-1,4benzoquinone; 2-(10-hydroxydecyl)-6-methoxy-3-methyl-5-(trideuteriomethoxy)cyclohexa-2,5-diene-1,4-dione
• Indication:
  In total 2 Indication(s)
  Cognitive impairment [ICD-11: 6D71]; Approved; [1]
  Friedreich's ataxia [ICD-11: 8A03]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Nonalcoholic fatty liver disease [ICD-11: DB92]; [1]
• Formula: C19H30O5
• IsoSMILES: CC1=C(C(=O)C(=C(C1=O)OC)OC)CCCCCCCCCCO
• InChI: 1S/C19H30O5/c1-14-15(12-10-8-6-4-5-7-9-11-13-20)17(22)19(24-3)18(23-2)16(14)21/h20H,4-13H2,1-3H3
• InChIKey: JGPMMRGNQUBGND-UHFFFAOYSA-N
• PubChem CID: 3686
• ChEBI ID: CHEBI:31687
• TTD Drug ID: D0MM8N
• INTEDE ID: DR0853
• DrugBank ID: DB09081

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-08: Nervous system diseases

Epilepsy [ICD-11: 8A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [2]

• Sensitive Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: IDB had successful control over drug resistance in the rotenone corneal kindled model by bypassing blocked complex I. IDB has a good safety profile and can be considered an adjuvant along with standard antiseizure drugs in drug-resistant patients.

Key Molecule: Quinone reductase 1 (NQO1) [2]

• Sensitive Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: IDB had successful control over drug resistance in the rotenone corneal kindled model by bypassing blocked complex I. IDB has a good safety profile and can be considered an adjuvant along with standard antiseizure drugs in drug-resistant patients.

ICD-09: Visual system diseases

Retinopathy [ICD-11: 9B71]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) [3]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [3]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Key Molecule: BCL2 associated X protein (BAX) [3]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Key Molecule: Beclin-1 (BECN1) [3]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

ICD-13: Digestive system diseases

Nonalcoholic fatty liver disease [ICD-11: DB92]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: SHC-transforming protein 1 (SHC1) [1]

• Resistant Disease: Nonalcoholic fatty liver disease [ICD-11: DB92.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Fast food diet (FFD) mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Glucose tolerance test (GTT); Insulin tolerance test (ITT)
• Mechanism Description: In the metabolic FFD model, idebenone administration improved insulin resistance, and reduced inflammation and fibrosis shown with qPCR, hydroxyproline measurement, and histology.

References

• Ref 1: Shc inhibitor idebenone ameliorates liver injury and fibrosis in dietary NASH in mice .J Biochem Mol Toxicol. 2021 Oct;35(10):e22876. doi: 10.1002/jbt.22876. Epub 2021 Aug 8. 10.1002/jbt.22876
• Ref 2: Attenuation of mitochondrial refractory epilepsy in rotenone corneal kindling model of drug resistance by idebenone: An approach to bypass mitochondrial complex I. Epilepsy Res. 2024 Nov;207:107458.
• Ref 3: Idebenone Attenuates Diabetic Retinopathy by Modulating Autophagy Via Targeting Akt Signaling. Curr Med Chem. 2024 Nov 1.