Drug Information

Drug (ID: DG00260) and It's Reported Resistant Information

• Name: Betulinic acid
• Synonyms: Betulinic acid; 472-15-1; Mairin; Betulic acid; NSC 113090; CCRIS 6748; 3-Hydroxylup-20(29)-en-28-oic acid; UNII-4G6A18707N; 3beta-Hydroxy-20(29)-lupaene-28-oic acid; EINECS 207-448-8; NSC677578; als-357; NSC 677578; CHEMBL269277; CHEBI:3087; 3beta-Hydroxy-lup-20(29)-en-28-oic acid; 4G6A18707N; Lup-20(29)-en-28-oic acid, 3-hydroxy-, (3beta)-; AK-72848; Lupatic Acid; SMR000445624
• Indication:
  In total 1 Indication(s)
  Melanoma [ICD-11: 2C30]; Phase 1; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Liver cancer [ICD-11: 2C12]; [1]
• Target: Herpes simplex virus DNA polymerase UL30 (HSV UL30); DPOL_HHV11; [1]
• Formula: C30H48O3
• IsoSMILES: CC(=C)[C@@H]1CC[C@]2([C@H]1[C@H]3CC[C@@H]4[C@]5(CC[C@@H](C([C@@H]5CC[C@]4([C@@]3(CC2)C)C)(C)C)O)C)C(=O)O
• InChI: 1S/C30H48O3/c1-18(2)19-10-15-30(25(32)33)17-16-28(6)20(24(19)30)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h19-24,31H,1,8-17H2,2-7H3,(H,32,33)/t19-,20+,21-,22+,23-,24+,27-,28+,29+,30-/m0/s1
• InChIKey: QGJZLNKBHJESQX-FZFNOLFKSA-N
• PubChem CID: 64971
• ChEBI ID: CHEBI:3087
• TTD Drug ID: D0R9YR
• DrugBank ID: DB12480

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

Liver cancer [ICD-11: 2C12]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-21 [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: p53/p66shc/miR21-Sod2 signaling pathway; Regulation; hsa05206
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; TUNEL assay; Promega
• Mechanism Description: p53 is responsible for the anti-tumor effect of betulinic acid through up-regulation of p66(shc) and miR-21 and down-regulation of Sod2 expression, leading to mitochondrial ROS accumulation and apoptosis.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Superoxide dismutase Mn (SODM) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: p53/p66shc/miR21-Sod2 signaling pathway; Regulation; hsa05206
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay; Promega
• Mechanism Description: p53 is responsible for the anti-tumor effect of betulinic acid through up-regulation of p66(shc) and miR-21 and down-regulation of Sod2 expression, leading to mitochondrial ROS accumulation and apoptosis.

References

• Ref 1: p53-p66(shc)/miR-21-Sod2 signaling is critical for the inhibitory effect of betulinic acid on hepatocellular carcinoma. Toxicol Lett. 2015 Nov 4;238(3):1-10. doi: 10.1016/j.toxlet.2015.07.016. Epub 2015 Jul 26.