2. Academic Validation
  3. Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe

Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe

  • Sci Rep. 2025 Oct 31;15(1):38188. doi: 10.1038/s41598-025-22011-4.
Jessica Teitel 1 2,  Margaret Farah 2,  Michele L Dziubinski 2,  Pil Lee 3,  Andrew White 3,  Alexander Sobeck 2,  Jose Colina 1 2,  John Takyi-Williams 4,  Bo Wen 5,  Elmar Nurmemmedov 6,  Ivan Babic 6,  Andre Monteiro da Rocha 7 8,  Karan Bedi 9,  Aaron Robida 10,  Grace McIntyre 1 2,  Takashi Hotta 11,  Yinzhi Lin 1 2,  Sreeja C Sekhar 1 2,  Ryoma Ohi 11,  Analisa DiFeo 12 13
Affiliations

Affiliations

  • 1 Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 2 Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 3 College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 4 Therapeutic Systems Research Laboratories (TSRL), Inc, Ann Arbor, MI, 48105, USA.
  • 5 Pharmacokinetics Core, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 6 CellarisBio, San Diego, CA, 92121, USA.
  • 7 Frankel Cardiovascular Center Cardiovascular Regeneration Core Laboratory, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 8 Internal Medicine, Cardiology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 9 Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 10 Center for Chemical Genomics, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 11 Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • 12 Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA. adifeo@med.umich.edu.
  • 13 Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA. adifeo@med.umich.edu.
PMID: 41173942 DOI: 10.1038/s41598-025-22011-4
Abstract

MYC overexpression is a well-established Cancer vulnerability, yet direct therapeutic targeting of Myc remains a challenge. Here, we identify DL78 as a potent antimitotic agent with selective Anticancer activity through its regulation of Myc. DL78 demonstrated broad efficacy by inhibiting growth across nine Cancer types and significantly reducing tumor burden in an in vivo model of platinum-resistant high-grade serous ovarian Cancer, with no overt toxicity. DL78 preferentially targets chromosomally unstable, MYC-overexpressing Cancer cells, a hallmark of high-grade serous ovarian Cancer. Mechanistically, DL78 exploits Myc's role in mitotic entry by disrupting its interaction with α-tubulin, leading to sustained mitotic arrest, mitotic catastrophe, and Apoptosis while sparing nonmalignant cells. This study establishes a novel paradigm for Myc-targeted therapy by introducing DL78, which induces cancer-selective mitotic catastrophe by disrupting Myc's interaction with α-tubulin rather than its transcriptional activity.

Keywords

G2-M arrest; High-grade serous ovarian cancer; Mitotic catastrophe; c-Myc; α-tubulin.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z