Drug Information

Drug (ID: DG00277) and It's Reported Resistant Information

• Name: Abexinostat
• Synonyms: PCI-24781; 783355-60-2; ABEXINOSTAT; PCI 24781; CRA-024781; CRA 024781; UNII-IYO470654U; 3-((dimethylamino)methyl)-N-(2-(4-(hydroxycarbamoyl)phenoxy)ethyl)benzofuran-2-carboxamide; CRA-02478; Abexinostat(PCI-24781); PCI-24781 (Abexinostat); Abexinostat (PCI-24781); IYO470654U; 3-[(Dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)carbonyl]phenoxy]ethyl]-2-benzofurancarboxamide; 3-((Dimethylamino)methyl)-N-(2-(4-(hydroxycarbamoyl)-phenoxy)ethyl)benzofuran-2-carboxamide
• Indication:
  In total 8 Indication(s)
  Follicular lymphoma [ICD-11: 2A80]; Phase 3; [1]
  Renal cell carcinoma [ICD-11: 2C90]; Phase 3; [1]
  Acute myeloid leukaemia [ICD-11: 2A60]; Phase 2; [1]
  Breast cancer [ICD-11: 2C60]; Phase 2; [1]
  Diffuse large B-cell lymphoma [ICD-11: 2A81]; Phase 2; [1]
  Gynecologic cancer [ICD-11: 2F33-2F76]; Phase 2; [1]
  Mature T-cell lymphoma [ICD-11: 2A90]; Phase 2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
• Target: Histone deacetylase (HDAC); NOUNIPROTAC; [1]
• Formula: C21H23N3O5
• IsoSMILES: CN(C)CC1=C(OC2=CC=CC=C21)C(=O)NCCOC3=CC=C(C=C3)C(=O)NO
• InChI: 1S/C21H23N3O5/c1-24(2)13-17-16-5-3-4-6-18(16)29-19(17)21(26)22-11-12-28-15-9-7-14(8-10-15)20(25)23-27/h3-10,27H,11-13H2,1-2H3,(H,22,26)(H,23,25)
• InChIKey: MAUCONCHVWBMHK-UHFFFAOYSA-N
• PubChem CID: 11749858
• ChEBI ID: CHEBI:92223
• TTD Drug ID: D0V0SL
• DrugBank ID: DB12565

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: X inactive specific transcript (XIST) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: HCC1954 cells; Breast; Homo sapiens (Human); CVCL_1259
• In Vitro Model: BrCa-MZ-01 cells; Breast; Homo sapiens (Human); CVCL_5495
• In Vitro Model: CRCM226X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: CRCM311X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: CRCM389X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: CRCM392X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: S68 cells; Breast; Homo sapiens (Human); CVCL_5585
• In Vitro Model: Sk-BR-7 cells; Breast; Homo sapiens (Human); CVCL_5218
• In Vitro Model: SUM149 cells; Breast; Homo sapiens (Human); CVCL_3422
• In Vitro Model: SUM159 cells; Breast; Homo sapiens (Human); CVCL_5423
• In Vitro Model: Xist med cells; Breast; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Abexinostat induced CSC differentiation in low-dose sensitive BCLs, whereas it did not have any effect on the CSC population from high-dose sensitive BCLs. Abexinostat effect is mediated at the cellular level through the modulation of the CSC pool. Only the PDX with low Xist expression displayed a significant decrease of its CSC population after abexinostat treatment, whereas HDACi treatment induced an increase of the CSC population in PDX with high Xist expression.

References

• Ref 1: The histone deacetylase inhibitor abexinostat induces cancer stem cells differentiation in breast cancer with low Xist expression. Clin Cancer Res. 2013 Dec 1;19(23):6520-31. doi: 10.1158/1078-0432.CCR-13-0877. Epub 2013 Oct 18.