Drug Information

Drug (ID: DG00034) and It's Reported Resistant Information

• Name: Abiraterone
• Synonyms: Abiraterone (AR inhibitor)
• Indication:
  In total 1 Indication(s)
  Prostate cancer [ICD-11: 2C82]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Prostate cancer [ICD-11: 2C82]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Prostate cancer [ICD-11: 2C82]; [2]
• Target: Steroid 17-alpha-monooxygenase (S17AH); CP17A_HUMAN; [1]
• Formula: C24H31NO
• IsoSMILES: C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4C5=CN=CC=C5)C)O
• InChI: 1S/C24H31NO/c1-23-11-9-18(26)14-17(23)5-6-19-21-8-7-20(16-4-3-13-25-15-16)24(21,2)12-10-22(19)23/h3-5,7,13,15,18-19,21-22,26H,6,8-12,14H2,1-2H3/t18-,19-,21-,22-,23-,24+/m0/s1
• InChIKey: GZOSMCIZMLWJML-VJLLXTKPSA-N
• PubChem CID: 132971
• ChEBI ID: CHEBI:68642
• TTD Drug ID: D02STN
• DrugBank ID: DB05812

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

Prostate cancer [ICD-11: 2C82]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA) [2]

• Resistant Disease: Castration-resistant prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 22Rv-1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• Experiment for Molecule Alteration: qRT-PCR; Western blot assay
• Experiment for Drug Resistance: Cell viability assay; Colony formation assay
• Mechanism Description: In conclusion, we reveals a novel regulator PPP1CA driving abiraterone resistance. The natural product nodularin-R ameliorates abiraterone resistance by inhibiting PPP1CA. The combination of nodularin-R and abiraterone exerts synergistic anti-CRPC effects.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Androgen receptor (AR) [1]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Structural variation; Copy number gain
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Whole genome sequencing assay; Exome sequencing assay
• Mechanism Description: Accordingly, AR amplification was detected in circulating cell-free DNA and was shown to be associated with enzalutamide and abiraterone treatment resistance in a cohort of 62 CRPC patients.

Key Molecule: Androgen receptor (AR) [1]

• Resistant Disease: Primary prostate cancer [ICD-11: 2C82.Z]
• Molecule Alteration: Structural variation; Copy number gain
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Whole genome sequencing assay; Exome sequencing assay
• Mechanism Description: Accordingly, AR amplification was detected in circulating cell-free DNA and was shown to be associated with enzalutamide and abiraterone treatment resistance in a cohort of 62 CRPC patients.

References

• Ref 1: Clonal origin and spread of metastatic prostate cancer. Endocr Relat Cancer. 2016 Apr;23(4):R207-17. doi: 10.1530/ERC-16-0049. Epub 2016 Mar 21.
• Ref 2: Nodularin-R Synergistically Enhances Abiraterone Against Castrate- Resistant Prostate Cancer via PPP1CA Inhibition. J Cell Mol Med. 2024 Nov;28(22):e70210.