Delving into the Latest Updates on SHetA2 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

HSC70 x HSPA5 x HSPA9

Action

modulators

Mechanism

HSC70 modulators(heat shock protein family A (Hsp70) member 8 modulators), HSPA5 modulators(78 kDa glucose-regulated protein modulators), HSPA9 modulators(heat shock protein family A (Hsp70) member 9 modulators)

Therapeutic Areas

Neoplasms

Active Indication

Relapsed Solid Neoplasm

Inactive Indication-

Originator Organization

University of Oklahoma

Active Organization

National Cancer Institute

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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ABSTRACTCervical cancer is predominantly driven by persistent infections with high‐risk human papillomavirus and the continuous activity of its E6 and E7 oncoproteins. This study explored the role of heat shock proteins 70 kDa (HSP70s) in enhancing the function of these oncoproteins and examined the impact of SHetA2, an investigational new drug, on this interaction. We found that HSP70 specifically binds to E7, but not E6, protein and that SHetA2 disrupts this binding. This disruption led to a significant reduction in E6 and E7 mRNA and E7 protein levels, while effects on E6 protein levels were minimal. SHetA2 treatment also resulted in altered levels of cell cycle regulatory proteins, reduced cell cycle progression, and decreased metabolic viability in cervical cancer cell lines and xenograft models. These findings support the potential of SHetA2 to impair cervical cancer progression by targeting HSP70/E7 interactions, highlighting its promise as a therapeutic strategy for treating cervical cancer.

01 Jan 2024·Gynecologic Oncology

Manipulation of metabolic responses enhances SHetA2 efficacy without toxicity in cervical cancer cell lines and xenografts

Article

Author: Benbrook, Doris Mangiaracina ; Lightfoot, Stanley ; Rai, Rajani

OBJECTIVEThe high frequency of cervical cancer recurrence after primary therapy necessitates alternative treatments. High-risk human papillomavirus (HR-HPV) causes cervical cancer and it's continued presence supports elevated metabolism, proliferation and survival of cancer cells. The low-to-no toxicity new investigational drug, SHetA2, counteracts high-risk human papillomavirus (HR-HPV) effects on cell proliferation and survival in cervical cancer cells and xenograft tumors by disrupting heat shock protein 70 chaperone protection of oncogenic proteins. Our objective was to study the involvement of metabolism in SHetA2 effects on cervical cancer cells and tumors.METHODSSHetA2-mediated proteomic and metabolic effects were measured in HR-HPV-positive CaSKi and SiHa and HR-HPV-negative C-33 A cervical cancer cell lines. Combined treatment with 2-deoxyglucose (2-DG) was evaluated in cell culture and SiHa xenografts.RESULTSSHetA2 inhibited oxidative phosphorylation (OxPhos) and altered levels of proteins involved in metabolism, protein synthesis, and DNA replication and repair. Cervical cancer cells responded by elevating glycolysis. Inhibition of the glycolytic responses using galactose media or 2-DG increased SHetA2 sensitivity of two HR-HPV-positive, but not an HR-HPV-negative cervical cancer cell line. Interaction of 2-DG and SHetA2 was synergistic in HR-HPV positive cell lines in association with augmentation of SHetA2 ATP reduction, but not SHetA2 DNA damage induction. These results were verified in a SiHa xenograft tumor model without evidence of toxicity.CONCLUSIONSCompensatory glycolysis counteracts OxPhos inhibition in SHetA2-treated HR-HPV-positive cervical cancer cell lines. Prevention of compensatory glycolysis with 2-DG or another glycolysis inhibitor has the potential to improve SHetA2 therapy without toxicity.

05 Aug 2021·Microbiology Resource Announcements

Complete Genome Sequence and Methylome of the Type Strain of Shewanella algae

Article

Author: Thorell, Kaisa ; Martín-Rodríguez, Alberto J. ; Krell, Tino ; Galperin, Michael Y. ; Römling, Ute ; Tellgren-Roth, Christian ; Sjöling, Åsa

We report the complete genome sequence and base modification analysis of the Shewanella algae type strain CECT 5071 (= OK-1 = ATCC 51192 = DSM 9167 = IAM 14159). The genome is composed of a single chromosome of 4,924,764 bp, with a GC content of 53.10%.

100 Deals associated with SHetA2

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