Drug Information

Drug (ID: DG00006) and It's Reported Resistant Information

• Name: Apigenin
• Synonyms: Apigenin; 520-36-5; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one; Chamomile; Versulin; Spigenin; Apigenol; 4',5,7-Trihydroxyflavone; Apigenine; C.I. Natural Yellow 1; 5,7,4'-Trihydroxyflavone; Pelargidenon 1449; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4-benzopyrone; 2-(p-Hydroxyphenyl)-5,7-dihydroxychromone; UCCF 031; NSC 83244; UNII-7V515PI7F6; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one; CCRIS 3789; CHEBI:18388; CHEMBL28; EINECS 208-292-3; 4H-1-Benzopyran-4-one, 5,7-di
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Investigative; [1]
• Target: Aldose reductase (AKR1B1); ALDR_HUMAN; [1]
• Target: Androgen receptor messenger RNA (AR mRNA); ANDR_HUMAN; [1]
• Target: Aromatase (CYP19A1); CP19A_HUMAN; [1]
• Target: Casein kinase II alpha (CSNK2A1); CSK21_HUMAN; [1]
• Target: Cyclin-dependent kinase 6 (CDK6); CDK6_HUMAN; [1]
• Target: Cytochrome P450 1B1 (CYP1B1); CP1B1_HUMAN; [1]
• Target: Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1); DHB1_HUMAN; [1]
• Target: Influenza Neuraminidase (Influ NA); NRAM_I33A0; [1]
• Target: Plasmodium CDK Pfmrk (Malaria Pfmrk); P90584_PLAFA; [1]
• Formula: C15H10O5
• IsoSMILES: C1=CC(=CC=C1C2=CC(=O)C3=C(C=C(C=C3O2)O)O)O
• InChI: 1S/C15H10O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-7,16-18H
• InChIKey: KZNIFHPLKGYRTM-UHFFFAOYSA-N
• PubChem CID: 5280443
• ChEBI ID: CHEBI:18388
• TTD Drug ID: D00RIX
• VARIDT ID: DR00822
• DrugBank ID: DB07352

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-423-5p [1]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Bax/BCL2/caspase-3 signaling pathway; Activation; hsa04933
• Cell Pathway Regulation: Mitochondrial signaling pathway; Regulation; N.A.
• In Vitro Model: CD133-positive cells; Brain; Homo sapiens (Human); CVCL_IR55
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Annexin V/PI apoptosis assay; Caspase-3 activity assay
• Mechanism Description: Retracted-miR423-5p knockdown enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.

ICD-05: Endocrine/nutritional/metabolic diseases

Type 2 diabetes mellitus [ICD-11: 5A11]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Endoplasmic reticulum chaperone BiP (HSPA5) [2]

• Sensitive Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: ER stress signalling pathway; Regulation; N.A.
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Glucose uptake assay
• Mechanism Description: In the present study, we identified apigenin as an effective compound for ameliorating ER stress and insulin resistance. It attenuated ER stress-induced cell death and hepatic insulin resistance and improved abnormal glucose tolerance in a db/db diabetic model. The molecular mechanism of apigenin involved direct binding to beta-tubulin and improving tubulin stability, thereby recovering insulin resistance and developing diabetes.

Key Molecule: DNA damage-inducible transcript 3 (DDIT3) [2]

• Sensitive Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: ER stress signalling pathway; Regulation; N.A.
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Glucose uptake assay
• Mechanism Description: In the present study, we identified apigenin as an effective compound for ameliorating ER stress and insulin resistance. It attenuated ER stress-induced cell death and hepatic insulin resistance and improved abnormal glucose tolerance in a db/db diabetic model. The molecular mechanism of apigenin involved direct binding to beta-tubulin and improving tubulin stability, thereby recovering insulin resistance and developing diabetes.

References

• Ref 1: miR-423-5p knockdown enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway. Tumour Biol. 2017 Apr;39(4):1010428317695526. doi: 10.1177/1010428317695526.
• Ref 2: A unique compound ameliorating endoplasmic reticulum stress and insulin resistance by binding to beta tubulin. FASEB J. 2024 Nov 15;38(21):e70150.