Drug Information

Drug (ID: DG02036) and It's Reported Resistant Information

• Name: Arenobufagin
• Synonyms: Arenobufagin|464-74-4|5-[(3S,5R,8R,9S,10S,11S,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-12-oxo-2,3,4,5,6,7,8,9,11,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]pyran-2-one|12-Oxo-3-beta,11-alpha,14-trihydroxy-5-beta-bufa-20,22-dienolide|27R42QLM25|3,11,14-trihydroxy-12-oxo-bufa-20,22-dienolide|5beta-Bufa-20,22-dienolide, 3beta,11alpha,14-trihydroxy-12-oxo-|5-beta-BUFA-20,22-DIENOLIDE, 12-OXO-3-beta,11-alpha,14-TRIHYDROXY-|Bufa-20,22-dienolide, 3,11,14-trihydroxy-12-oxo-, (3beta,5beta,11alpha)-|5-((3S,5R,8R,9S,10S,11S,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-12-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2H-pyran-2-one|5-((3S,5R,10S,11S,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-12-oxo-2,3,4,5,6,7,8,9,11,15,16,17-dodecahydro-1H-cyclopenta(a)phenanthren-17-yl)pyran-2-one|5-((3S,5R,8R,9S,10S,11S,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-12-oxo-2,3,4,5,6,7,8,9,11,15,16,17-dodecahydro-1H-cyclopenta(a)phenanthren-17-yl)pyran-2-one|5-(5,11,17-trihydroxy-2,15-dimethyl-16-oxotetracyclo(8.7.0.02,7.011,15)heptadecan-14-yl)-2H-pyran-2-one|5-[(3S,5R,10S,11S,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-12-oxo-2,3,4,5,6,7,8,9,11,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]pyran-2-one|5-{5,11,17-trihydroxy-2,15-dimethyl-16-oxotetracyclo[8.7.0.02,7.011,15]heptadecan-14-yl}-2H-pyran-2-one|UNII-27R42QLM25|12-Oxo-3-.beta.,11-.alpha.,14-trihydroxy-5-.beta.-bufa-20,22-dienolide|5.beta.-Bufa-20,22-dienolide, 3.beta.,11.alpha.,14-trihydroxy-12-oxo-|CHEMBL4086974|SCHEMBL21578402|DTXSID00963565|5-.beta.-Bufa-20,22-dienolide, 12-oxo-3-.beta.,11-.alpha.,14-trihydroxy-|Bufa-20,22-dienolide, 3,11,14-trihydroxy-12-oxo-, (3.beta.,5.beta.,11.alpha.)-|CHEBI:197067|GLXC-13270|HY-N0876|AKOS030526814|CS-3693|FA74189|NCGC00485924-01|AC-34734|AS-76734|DA-50681|C20035|(3beta,5beta,11alpha)-3,11,14-Trihydroxy-12-oxobufa-20,22-dienolide|Bufa-20,22-dienolide, 3,11,14-trihydroxy-12-oxo- (3-beta,5-beta,11-alpha)-|Bufa-20,22-dienolide, 3,11,14-trihydroxy-12-oxo-(3-beta,5-beta,11-alpha)-|5-((3S,5R,10S,11S,13R,14S,17R)-3,11,14-trihydroxy-10,13-dimethyl-12-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2H-pyran-2-one
• Indication:
  In total 1 Indication(s)
  . .; .
• Formula: C24H32O6
• IsoSMILES: C[C@]12CC[C@@H](C[C@H]1CC[C@@H]3[C@@H]2[C@@H](C(=O)[C@]4([C@@]3(CC[C@@H]4C5=COC(=O)C=C5)O)C)O)O
• InChI: InChI=1S/C24H32O6/c1-22-9-7-15(25)11-14(22)4-5-17-19(22)20(27)21(28)23(2)16(8-10-24(17,23)29)13-3-6-18(26)30-12-13/h3,6,12,14-17,19-20,25,27,29H,4-5,7-11H2,1-2H3/t14-,15+,16-,17-,19-,20+,22+,23+,24+/m1/s1
• InChIKey: JGDCRWYOMWSTFC-AZGSIFHYSA-N
• PubChem CID: 12305198

Type(s) of Resistant Mechanism of This Drug

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Liver cancer [ICD-11: 2C12]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Proprotein convertase subtilisin/kexin type 9 (PCSK9) [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.96E-09; Fold-change: 4.92E-01; Z-score: 5.99E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cholesterol metabolism; Activation; hsa04979
• In Vivo Model: Hepa1-6 hepatocellular carcinoma transplanted tumor model mice; Mice
• Experiment for Molecule Alteration: Western blot analysis and immunohistochemical assays
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: ARBU significantly inhibited the proliferation of Hepa1-6 in vivo and in vitro, regulated cholesterol metabolism, and promoted the M1-type polarization of macrophages in the tumor microenvironment. ARBU inhibits cholesterol synthesis in the TME through the PCSK9/LDL-R signaling pathway, thereby blocking macrophage M2 polarization, promoting apoptosis of the tumor cells, and inhibiting their proliferation and migration.

Key Molecule: Proprotein convertase subtilisin/kexin type 9 (PCSK9) [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.96E-09; Fold-change: 4.92E-01; Z-score: 5.99E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cholesterol metabolism; Activation; hsa04979
• In Vitro Model: Hepa1-6 cells; Liver; Mus musculus (Mouse); CVCL_0327
• Experiment for Molecule Alteration: Western blot analysis and immunohistochemical assays
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: ARBU significantly inhibited the proliferation of Hepa1-6 in vivo and in vitro, regulated cholesterol metabolism, and promoted the M1-type polarization of macrophages in the tumor microenvironment. ARBU inhibits cholesterol synthesis in the TME through the PCSK9/LDL-R signaling pathway, thereby blocking macrophage M2 polarization, promoting apoptosis of the tumor cells, and inhibiting their proliferation and migration.

References

• Ref 1: Arenobufagin modulation of PCSK9-mediated cholesterol metabolism induces tumor-associated macrophages polarisation to inhibit hepatocellular carcinoma progression. Phytomedicine. 2024 Jun;128:155532.