Delving into the Latest Updates on KT-531 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

HDAC6

Action

inhibitors

Mechanism

HDAC6 inhibitors(Histone deacetylase 6 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

T-Cell Prolymphocytic Leukemia

Inactive Indication-

Originator Organization

The University of Toronto Mississauga

Active Organization

The University of Toronto Mississauga

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Bukhari, Shazreh ; Sorger, Helena ; de Araujo, Elvin D. ; Israelian, Johan ; Nawar, Nabanita ; Mustjoki, Satu ; Bhatti, Muzaffar N. ; Hassan, Muhammad Murtaza ; Timonen, Sanna ; Moriggl, Richard ; Neubauer, Heidi A. ; Shouksmith, Andrew E. ; Gawel, Justyna M. ; Sedighi, Abootaleb ; Geletu, Mulu ; Abdeldayem, Ayah ; Manaswiyoungkul, Pimyupa ; Raouf, Yasir S. ; Ianevski, Aleksandr ; Krämer, Oliver H. ; von Jan, Jana ; Herling, Marco ; Aittokallio, Tero ; Toutah, Krimo ; Radu, Tudor B. ; Olaoye, Olasunkanmi O. ; Gunning, Patrick T.

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where HDAC6 was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as stand-alone or in combination with targeted drugs.

100 Deals associated with KT-531

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