Development of hybrid aptamers-engineered PROTACs for degrading VEGF165 in both tumor- and vascular endothelial cells DOI

Ziting Feng,

Duoli Xie,

Fang Qiu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 281, P. 117027 - 117027

Published: Nov. 2, 2024

Language: Английский

Targeting Oncogenic Transcriptional Factor c-Myc by Oligonucleotide PROTAC for the Treatment of Hepatocellular Carcinoma DOI
Min Ai,

Hulin Ma,

Jianhua He

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 280, P. 116978 - 116978

Published: Oct. 18, 2024

Language: Английский

Citations

2
Oral Administration of Cancer Vaccines: Challenges and Future Perspectives DOI Creative Commons
Marta Gambirasi, Amin Safa,

Idris Vruzhaj

et al.

Vaccines, Journal Year: 2023, Volume and Issue: 12(1), P. 26 - 26

Published: Dec. 26, 2023

Cancer vaccines, a burgeoning strategy in cancer treatment, are exploring innovative administration routes to enhance patient and medical staff experiences, as well immunological outcomes. Among these, oral has surfaced particularly noteworthy approach, which is attributed its capacity ignite both humoral cellular immune responses at systemic mucosal tiers, thereby potentially bolstering vaccine efficacy comprehensively durably. Notwithstanding this, the deployment of vaccines through route clinical context impeded by multifaceted challenges, predominantly stemming from intricacy orchestrating effective immunogenicity necessitating strategic navigation gastrointestinal barriers. Based on tract, this review critically analyses challenges recent advances provides insights into future development vaccines.

Language: Английский

Citations

2
Design of Mdm2 Protac Degraders with a Built-In Tumor-Targeting Ability DOI
Zhuqian Wang,

Siran Yue,

Xinxin Chen

et al.

Published: Jan. 1, 2024

MDM2 is a negative regulator of tumor suppressor p53 and serves as therapeutic target for various cancers. Currently, there are no clinically available antitumor drugs modulating MDM2-p53 signaling because the existing inhibitors have limited efficacy excessive toxicity. PROTACs heterobifunctional molecules recruiting E3 ligases proteins interest (POIs) to induce proteasomal degradation POIs. PROTAC degraders provide better potency but still cannot address safety concern due lack tumor-targeting ability. AS1411 -penetrating aptamer that specifically recognizes nucleolin (NCL), shuttling protein overexpressed on surface cells mediates cellular internalization AS1411. Moreover, NCL within has been shown be binding partner MDM2. Inspired by this, we recently repurposed new recruiter employing molecular bridge. In this study, designed molecule AS1411-VH032 via conjugating with VH032, ligand ligase VHL. realizes tumor-selective MDM2, leading obvious shrinkage detectable Besides being target, also an harnessed PROTACs. Thus, developed AS1411-based homo-PROTAC homoAS1411, which induces tumor-specific suicide prevents progression without causing Both homoAS1411 promising built-in ability, balances favorable profile.Funding: This work supported National Natural Science Foundation Council China (82172386 81922081 CL), 2020 Guangdong Provincial Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab) (2020B1212030006 AL), Basic Applied Research (2022A1515012164 Science, Technology, Commission Shenzhen (JCYJ20210324104201005 Hong Kong General (12102722 RGC Theme-based Scheme (T12-201/20-R LingGene Biotech Co., Ltd.Declaration Interest: The Ltd patent application related work.Ethical Approval: procedures all in vivo studies gained ethics approval from Institutional Animal Care Use Committee (IACUC) Southern University Technology. We affirmed had relevant ethical regulations animal testing research study.

Language: Английский

Citations

0
Enhancing photodynamic and radionuclide therapy by small interfering RNA (siRNA)-RAD51 transfection via self-emulsifying delivery systems (SNEDDS) DOI

Ulises Paredes-Hernández,

Leslie V. Aguilar-Peña,

Keila Isaac‐Olivé

et al.

Cytotherapy, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

0
Design of Murine Double Minute 2 Proteolysis Targeting Chimera Degraders with a Built-In Tumor-Targeting Ability DOI
Zhuqian Wang,

Siran Yue,

Xinxin Chen

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(21), P. 18865 - 18882

Published: Oct. 22, 2024

Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules to induce the proteasomal degradation of target proteins. Currently, there no tumor-targeting PROTACs for modulating oncogenic murine double minute 2 (MDM2). AS1411 is a aptamer that specifically recognizes nucleolin (NCL) overexpressed on surface tumor cells. We recently repurposed as an MDM2 recruiter since it could form NCL-bridged ternary complex with MDM2. In this study, we design PROTAC molecule AS1411-VH032 via conjugating von Hippel-Lindau (VHL) ligase VH032. facilitates tumor-selective MDM2, leading shrinkage detectable toxicity. Besides being molecular target, also serves E3 harnessed by PROTACs. Thus, developed AS1411-based homo-PROTAC homoAS1411, which induces tumor-specific suicide and prevents progression without causing side effects. Both homoAS1411 promising degraders built-in ability, balances antitumor efficacy favorable safety profile.

Language: Английский

Citations

0
Development of hybrid aptamers-engineered PROTACs for degrading VEGF165 in both tumor- and vascular endothelial cells DOI

Ziting Feng,

Duoli Xie,

Fang Qiu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 281, P. 117027 - 117027

Published: Nov. 2, 2024

Language: Английский

Citations

0