Drug Information

Drug (ID: DG00324) and It's Reported Resistant Information

• Name: Bendamustine hydrochloride
• Synonyms: Treanda (TN)
• Indication:
  In total 1 Indication(s)
  Leukaemia [ICD-11: 2A60-2B33]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Chronic lymphocytic leukemia [ICD-11: 2A82]; [1]
  Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]; [3]
• Target: Human Deoxyribonucleic acid (hDNA); NOUNIPROTAC; [1]
• Formula: C16H21Cl2N3O2
• IsoSMILES: CN1C2=C(C=C(C=C2)N(CCCl)CCCl)N=C1CCCC(=O)O
• InChI: 1S/C16H21Cl2N3O2/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23/h5-6,11H,2-4,7-10H2,1H3,(H,22,23)
• InChIKey: YTKUWDBFDASYHO-UHFFFAOYSA-N
• PubChem CID: 65628
• TTD Drug ID: D01CYA
• INTEDE ID: DR0188
• DrugBank ID: DB06769

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Chronic lymphocytic leukemia [ICD-11: 2A82]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Resistant Disease: Chronic lymphocytic leukemia [ICD-11: 2A82.0]
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Whole exome sequencing assay; Targeted deep sequencing assay; Sanger sequencing assay
• Mechanism Description: Following exposure to chemoimmunotherapy, the resistant TP53 aberrant clones accumulate and dominate the tumour.

Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: CXC chemokine receptor type 4 (CXCR4) [3]

• Resistant Disease: Waldenstrom macroglobulinemia [ICD-11: 2A85.4]
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: CXCR4 mutation led to bendamustine in the waldenstrom macroglobulinemia.

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase PLK1 (PLK1) [2]

• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Molecule Alteration: Expression; Down-regulation
• Mechanism Description: Bendamustine-resistant leukemia cells exhibited a decreased RNA expression level for Polo-like kinase-1 (PLK-1). Notably, after treatment with the demethylating agent 5-aza-2'-deoxycytidine, PLK-1 gene expression surged significantly, enhancing bendamustine's cytotoxicity in the resistant leukemia cells. However, MDR1 expression, as determined by flow cytometry, remained consistent between parental and bendamustine-resistant leukemia cells.

References

• Ref 1: Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease. Leukemia. 2016 Jun;30(6):1301-10. doi: 10.1038/leu.2016.10. Epub 2016 Feb 5.
• Ref 2: Methylation of PLK-1 Potentially Drives Bendamustine Resistance in Leukemia Cells. J Nippon Med Sch. 2024 May 21;91(2):162-171.
• Ref 3: Genomics, Signaling, and Treatment of Waldenstr m Macroglobulinemia .J Clin Oncol. 2017 Mar 20;35(9):994-1001. doi: 10.1200/JCO.2016.71.0814. Epub 2017 Feb 13. 10.1200/JCO.2016.71.0814