Drug Information

Drug (ID: DG01209) and It's Reported Resistant Information

• Name: Eribulin
• Synonyms: Eribulin; 253128-41-5; Halaven; UNII-LR24G6354G; ER 086526; CHEBI:63587; LR24G6354G; 2-(3-Amino-2-hydroxypropyl)hexacosahydro-3-methoxy-26-methyl-20,27-bis(methylene)11,15-18,21-24,28-triepoxy-7,9-ethano-12,15-methano-9H,15H-furo(3,2-i)furo(2',3'-5,6)pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4H)-one; (1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-amino-2-hydroxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.13,32.13,33.16,9.112,16.018,22.029,36.031,35]hentetracontan-24-one; Eribulin [INN]; (1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,35R,36S)-20-[(2S)-3-amino-2-hydroxypropyl]-21-methoxy-14-methyl-8,15-bis(methylene)-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.1(3,32).1(3,33).1(6,9).1(12,16).0(18,22).0(29,36).0(31,35)]hentetracontan-24-one; NSC-707389; ER-086526; (1s,3s,6s,9s,12s,14r,16r,18s,20r,21r,22s,26r,29s,31r,32s,33r,35r,36s)-20-[(2s)-3-Amino-2-Hydroxypropyl]-21-Methoxy-14-Methyl-8,15-Dimethylidene-2,19,30,34,37,39,40,41-Octaoxanonacyclo[24.9.2.1~3,32~.1~3,33~.1~6,9~.1~12,16~.0~18,22~.0~29,36~.0~31,35~]hentetracontan-24-One (Non-Preferred Name); B 1939; e7389-lf; GTPL6813; CHEMBL1683590; SCHEMBL15783821; DTXSID101009321; ZINC169344691; DB08871; NCGC00510497-02; HY-13442; Q408717; (1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-amino-2-hydroxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.13,32.13,33.16,9.112,16.018,22.029,36.031,35]hentetracontan-24-o
• Indication:
  In total 1 Indication(s)
  Breast cancer [ICD-11: 2C60]; Approved; [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: Tubulin (TUB); NOUNIPROTAC; [1]
• Formula: C40H59NO11
• IsoSMILES: C[C@@H]1C[C@@H]2CC[C@H]3C(=C)C[C@@H](O3)CC[C@]45C[C@@H]6[C@H](O4)[C@H]7[C@@H](O6)[C@@H](O5)[C@@H]8[C@@H](O7)CC[C@@H](O8)CC(=O)C[C@H]9[C@H](C[C@H](C1=C)O2)O[C@@H]([C@@H]9OC)C[C@@H](CN)O
• InChI: 1S/C40H59NO11/c1-19-11-24-5-7-28-20(2)12-26(45-28)9-10-40-17-33-36(51-40)37-38(50-33)39(52-40)35-29(49-37)8-6-25(47-35)13-22(42)14-27-31(16-30(46-24)21(19)3)48-32(34(27)44-4)15-23(43)18-41/h19,23-39,43H,2-3,5-18,41H2,1,4H3/t19-,23+,24+,25-,26+,27+,28+,29+,30-,31+,32-,33-,34-,35+,36+,37+,38-,39+,40+/m1/s1
• InChIKey: UFNVPOGXISZXJD-JBQZKEIOSA-N
• PubChem CID: 11354606
• ChEBI ID: CHEBI:63587
• TTD Drug ID: D0KK2E
• INTEDE ID: DR0601
• DrugBank ID: DB08871

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

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

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatidylinositol 3-kinase (PI3K) [1]

• Resistant Disease: HER2 positive breast cancer [ICD-11: 2C60.8]
• Molecule Alteration: Function; Activation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Breast cancer cells; Breast; Homo sapiens (Human); N.A.
• In Vivo Model: Patient-derived tumour xenograft model; Mus musculus
• Experiment for Molecule Alteration: Targeted exome sequencing assay; Western blot analysis
• Experiment for Drug Resistance: Crystal violet cell proliferation assay
• Mechanism Description: PI3K activation promotes resistance to eribulin in HER2-negative breast cancer.

Key Molecule: Cyclin-dependent kinase inhibitor 1A (CDKN1A) [2]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Notch signaling pathway; Activation; hsa04330
• Cell Pathway Regulation: JAK-STAT signaling pathway; Activation; hsa04630
• In Vitro Model: MCF-7 ER cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Annexin V/PI assay; MTT assay
• Mechanism Description: We confirmed that BYL-719 could inhibit BCSC-like cell proliferation in 3D cultures and that the stemness characteristics of BCSC-like cells were inhibited. The PI3K/AKT/mTOR signaling pathway could be inhibited by BYL-719, and the Notch, JAK-STAT and MAPK/ERK signaling pathways which have crosstalk in the tumor microenvironment (TME) are also inhibited. By comparing eribulin-resistant breast cancer cell lines, we confirmed that BYL-719 could effectively overcome drug resistance.

Key Molecule: Transcription factor HES-1 (HES1) [2]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Notch signaling pathway; Activation; hsa04330
• Cell Pathway Regulation: JAK-STAT signaling pathway; Activation; hsa04630
• In Vitro Model: MCF-7 ER cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Annexin V/PI assay; MTT assay
• Mechanism Description: We confirmed that BYL-719 could inhibit BCSC-like cell proliferation in 3D cultures and that the stemness characteristics of BCSC-like cells were inhibited. The PI3K/AKT/mTOR signaling pathway could be inhibited by BYL-719, and the Notch, JAK-STAT and MAPK/ERK signaling pathways which have crosstalk in the tumor microenvironment (TME) are also inhibited. By comparing eribulin-resistant breast cancer cell lines, we confirmed that BYL-719 could effectively overcome drug resistance.

References

• Ref 1: PI3K activation promotes resistance to eribulin in HER2-negative breast cancer .Br J Cancer. 2021 Apr;124(9):1581-1591. doi: 10.1038/s41416-021-01293-1. Epub 2021 Mar 15. 10.1038/s41416-021-01293-1
• Ref 2: Effects of BYL-719 (alpelisib) on human breast cancer stem cells to overcome drug resistance in human breast cancer. Front Pharmacol. 2024 Oct 14;15:1443422.