BH4 domain of Bcl-2 as a novel target for cancer therapy

Zhiqing Liu, Christopher Wild, Ye Ding, Na Ye, Haiying Chen, Eric A. Wold, Jia Zhou

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Overexpression of B cell lymphoma 2 (Bcl-2) proteins is associated with therapy resistance in various human cancers. Traditional approaches target the Bcl-2 homology (BH)3 domain of Bcl-2; however, the BH4 domain represents a superior therapeutic target in light of its unique structure and crucial involvement in many cellular functions. In this critical review, we focus on the structural and functional basis of targeting the BH4 domain of Bcl-2, and highlight the recent advances in drug discovery efforts toward small-molecule BH4 domain inhibitors (e.g. BDA-366). The proof-of-concept studies support the hypothesis that targeting the BH4 domain of Bcl-2 holds promise to offer a novel anticancer therapy through the induction of apoptosis and an increased potential to overcome therapeutic resistance.

Original languageEnglish (US)
Pages (from-to)989-996
Number of pages8
JournalDrug Discovery Today
Issue number6
StatePublished - Jun 1 2016

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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