Zhong-Yin Zhang
Purdue University
H-index: 95
North America-United States
Description
Zhong-Yin Zhang, With an exceptional h-index of 95 and a recent h-index of 40 (since 2020), a distinguished researcher at Purdue University, specializes in the field of Protein tyrosine phosphatases, cell signaling, chemical biology & drug discovery.
His recent articles reflect a diverse array of research interests and contributions to the field:
Natural product-inspired molecules for covalent inhibition of SHP2 tyrosine phosphatase
Discovery of a selective TC-PTP degrader for cancer immunotherapy
Discovery of a SHP2 Degrader with In Vivo Anti-Tumor Activity
PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371
A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity
Driving axon regeneration by orchestrating neuronal and non-neuronal innate immune responses via the IFNγ-cGAS-STING axis
Small Molecule Degraders of Protein Tyrosine Phosphatase 1B and T‐Cell Protein Tyrosine Phosphatase for Cancer Immunotherapy
Inhibition of PRMT5 by market drugs as a novel cancer therapeutic avenue
Professor Information
University | Purdue University |
---|---|
Position | ___ |
Citations(all) | 27237 |
Citations(since 2020) | 6647 |
Cited By | 22925 |
hIndex(all) | 95 |
hIndex(since 2020) | 40 |
i10Index(all) | 263 |
i10Index(since 2020) | 161 |
University Profile Page | Purdue University |
Research & Interests List
Protein tyrosine phosphatases
cell signaling
chemical biology & drug discovery
Top articles of Zhong-Yin Zhang
Natural product-inspired molecules for covalent inhibition of SHP2 tyrosine phosphatase
Natural products have been playing indispensable roles in the development of lifesaving drug molecules. They are also valuable sources for covalent protein modifiers. However, they often are scarce in nature and have complex chemical structures, which are limiting their further biomedical development. Thus, natural product-inspired small molecules which still contain the essence of the parent natural products but are readily available and amenable for structural modification, are important and desirable in searching for lead compounds for various disease treatment. Inspired by the complex and diverse ent-kaurene diterpenoids with significant biological activities, we have created a synthetically accessible and focused covalent library by incorporating the bicyclo[3.2.1]octane α-methylene ketone, which is considered as the pharmacophore of ent-kaurene diterpenoids, as half of the structure, and replacing the …
Authors
Weida Liang,Aaron D Krabill,Katelyn S Gallagher,Christine Muli,Zihan Qu,Darci Trader,Zhong-Yin Zhang,Mingji Dai
Journal
Tetrahedron
Published Date
2024/3/2
Discovery of a selective TC-PTP degrader for cancer immunotherapy
T-cell protein tyrosine phosphatase (TC-PTP), encoded by PTPN2, has emerged as a promising target for cancer immunotherapy. TC-PTP deletion in B16 melanoma cells promotes tumor cell antigen presentation, while loss of TC-PTP in T-cells enhances T-cell receptor (TCR) signaling and stimulates cell proliferation and activation. Therefore, there is keen interest in developing TC-PTP inhibitors as novel immunotherapeutic agents. Through rational design and systematic screening, we discovered the first highly potent and selective TC-PTP PROTAC degrader, TP1L, which induces degradation of TC-PTP in multiple cell lines with low nanomolar DC50s and >110-fold selectivity over the closely related PTP1B. TP1L elevates the phosphorylation level of TC-PTP substrates including pSTAT1 and pJAK1, while pJAK2, the substrate of PTP1B, is unaffected by the TC-PTP degrader. TP1L also intensifies interferon …
Authors
Zhang ZY Miao J,Dong J,Miao Y,Bai Y,Qu Z,Jassim BA,Huang B,Nguyen Q,Ma Y,Murray AA,Li J,Low PS
Journal
Chemical Science
Published Date
2023/10/24
Discovery of a SHP2 Degrader with In Vivo Anti-Tumor Activity
Src homology 2 domain-containing phosphatase 2 (SHP2) is an attractive target for cancer therapy due to its multifaceted roles in both tumor and immune cells. Herein, we designed and synthesized a novel series of proteolysis targeting chimeras (PROTACs) using a SHP2 allosteric inhibitor as warhead, with the goal of achieving SHP2 degradation both inside the cell and in vivo. Among these molecules, compound P9 induces efficient degradation of SHP2 (DC50 = 35.2 ± 1.5 nM) in a concentration- and time-dependent manner. Mechanistic investigation illustrates that the P9-mediated SHP2 degradation requires the recruitment of the E3 ligase and is ubiquitination- and proteasome-dependent. P9 shows improved anti-tumor activity in a number of cancer cell lines over its parent allosteric inhibitor. Importantly, administration of P9 leads to a nearly complete tumor regression in a xenograft mouse model, as a result of robust SHP2 depletion and suppression of phospho-ERK1/2 in the tumor. Hence, P9 represents the first SHP2 PROTAC molecule with excellent in vivo efficacy. It is anticipated that P9 could serve not only as a new chemical tool to interrogate SHP2 biology but also as a starting point for the development of novel therapeutics targeting SHP2.
Authors
Zhang ZY Miao J,Bai Y,Miao Y,Qu Z,Dong J,Zhang RY,Aggarwal D,Jassim BA,Nguyen Q
Journal
Molecules
Published Date
2023/10
PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371
Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown. We discovered that genetic and pharmacological inhibition of PRL2 significantly reduce the burden of FLT3-internal tandem duplications–driven leukemia and extend the survival of leukemic mice. Furthermore, we found that PRL2 enhances oncogenic FLT3 signaling in leukemia cells, promoting their proliferation and survival. Mechanistically, PRL2 dephosphorylates the E3 ubiquitin ligase CBL at tyrosine 371 and attenuates CBL-mediated ubiquitination and …
Authors
H Chen,Bai,Y.,et al.
Journal
Blood
Published Date
2023/1/19
A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity
The inhibition of protein tyrosine phosphatases 1B (PTP1B) and N2 (PTPN2) has emerged as an exciting approach for bolstering T cell anti-tumor immunity. ABBV-CLS-484 is a PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. Here we have explored the therapeutic potential of a related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2 that enhances T cell recruitment and activation and represses the growth of tumors in mice, without promoting overt immune-related toxicities. The enhanced anti-tumor immunity in immunogenic tumors can be ascribed to the inhibition of PTP1B/PTPN2 in T cells, whereas in cold tumors, Compound-182 elicited direct effects on both tumor cells and T cells. Importantly, treatment with Compound-182 rendered otherwise resistant tumors sensitive to α-PD-1 therapy …
Authors
Shuwei Liang,Eric Tran,Xin Du,Jiajun Dong,Harrison Sudholz,Hao Chen,Zihan Qu,Nicholas D Huntington,Jeffrey J Babon,Nadia J Kershaw,Zhong-Yin Zhang,Jonathan B Baell,Florian Wiede,Tony Tiganis
Journal
Nature Communications
Published Date
2023/7/27
Driving axon regeneration by orchestrating neuronal and non-neuronal innate immune responses via the IFNγ-cGAS-STING axis
The coordination mechanism of neural innate immune responses for axon regeneration is not well understood. Here, we showed that neuronal deletion of protein tyrosine phosphatase non-receptor type 2 sustains the IFNγ-STAT1 activity in retinal ganglion cells (RGCs) to promote axon regeneration after injury, independent of mTOR or STAT3. DNA-damage-induced cGAMP synthase (cGAS)-stimulator of interferon genes (STINGs) activation is the functional downstream signaling. Directly activating neuronal STING by cGAMP promotes axon regeneration. In contrast to the central axons, IFNγ is locally translated in the injured peripheral axons and upregulates cGAS expression in Schwann cells and infiltrating blood cells to produce cGAMP, which promotes spontaneous axon regeneration as an immunotransmitter. Our study demonstrates that injured peripheral nervous system (PNS) axons can direct the …
Authors
Xu Wang,Chao Yang,Xuejie Wang,Jinmin Miao,Weitao Chen,Yiren Zhou,Ying Xu,Yongyan An,Aifang Cheng,Wenkang Ye,Mengxian Chen,Dong Song,Xue Yuan,Jiguang Wang,Peiyuan Qian,Angela Ruohao Wu,Zhong-Yin Zhang,Kai Liu
Journal
Neuron
Published Date
2023/1/18
Small Molecule Degraders of Protein Tyrosine Phosphatase 1B and T‐Cell Protein Tyrosine Phosphatase for Cancer Immunotherapy
Protein tyrosine phosphatase 1B (PTP1B) and T‐cell protein tyrosine phosphatase (TC‐PTP) play non‐redundant negative regulatory roles in T‐cell activation, tumor antigen presentation, insulin and leptin signaling, and are potential targets for several therapeutic applications. Here, we report the development of a highly potent and selective small molecule degrader DU‐14 for both PTP1B and TC‐PTP. DU‐14 mediated PTP1B and TC‐PTP degradation requires both target protein(s) and VHL E3 ligase engagement and is also ubiquitination‐ and proteasome‐dependent. DU‐14 enhances IFN‐γ induced JAK1/2‐STAT1 pathway activation and promotes MHC‐I expression in tumor cells. DU‐14 also activates CD8+ T‐cells and augments STAT1 and STAT5 phosphorylation. Importantly, DU‐14 induces PTP1B and TC‐PTP degradation in vivo and suppresses MC38 syngeneic tumor growth. The results indicate that …
Authors
Jiajun Dong,Jinmin Miao,Yiming Miao,Zihan Qu,Sheng Zhang,Peipei Zhu,Florian Wiede,Brenson A Jassim,Yunpeng Bai,Quyen Nguyen,Jianping Lin,Lan Chen,Tony Tiganis,W Andy Tao,Zhong‐Yin Zhang
Journal
Angewandte Chemie International Edition
Published Date
2023/5/22
Inhibition of PRMT5 by market drugs as a novel cancer therapeutic avenue
Market drugs, such as Food and Drug Administration (FDA) or European Medicines Agency (EMA)-approved drugs for specific indications provide opportunities for repurposing for newer therapeutics. This potentially saves resources invested in clinical trials that verify drug safety and tolerance in humans prior to alternative indication approval. Protein arginine methyltransferase 5 (PRMT5) overexpression has been linked to promoting the tumor phenotype in several cancers, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and breast cancer (BC), making PRMT5 an important target for cancer therapy. Previously, we showed that PRMT5-mediated methylation of the nuclear factor (NF)-κB, partially contributes to its constitutive activation observed in cancers. In this study, we utilized an AlphaLISA-based high-throughput screening method adapted in our lab, and identified one FDA …
Authors
Lakshmi Prabhu,Matthew Martin,Lan Chen,Özlem Demir,Jiamin Jin,Xiumei Huang,Aishat Motolani,Mengyao Sun,Guanglong Jiang,Harikrishna Nakshatri,Melissa L Fishel,Steven Sun,Ahmad Safa,Rommie E Amaro,Mark R Kelley,Yunlong Liu,Zhong-Yin Zhang,Tao Lu
Journal
Genes & Diseases
Published Date
2023/1/1
Professor FAQs
What is Zhong-Yin Zhang's h-index at Purdue University?
The h-index of Zhong-Yin Zhang has been 40 since 2020 and 95 in total.
What are Zhong-Yin Zhang's top articles?
The articles with the titles of
Natural product-inspired molecules for covalent inhibition of SHP2 tyrosine phosphatase
Discovery of a selective TC-PTP degrader for cancer immunotherapy
Discovery of a SHP2 Degrader with In Vivo Anti-Tumor Activity
PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371
A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity
Driving axon regeneration by orchestrating neuronal and non-neuronal innate immune responses via the IFNγ-cGAS-STING axis
Small Molecule Degraders of Protein Tyrosine Phosphatase 1B and T‐Cell Protein Tyrosine Phosphatase for Cancer Immunotherapy
Inhibition of PRMT5 by market drugs as a novel cancer therapeutic avenue
...
are the top articles of Zhong-Yin Zhang at Purdue University.
What are Zhong-Yin Zhang's research interests?
The research interests of Zhong-Yin Zhang are: Protein tyrosine phosphatases, cell signaling, chemical biology & drug discovery
What is Zhong-Yin Zhang's total number of citations?
Zhong-Yin Zhang has 27,237 citations in total.
What are the co-authors of Zhong-Yin Zhang?
The co-authors of Zhong-Yin Zhang are Gen-Sheng Feng, Michael Cowley, Tony Tiganis, Alvan Hengge, Mark A Saper, Ph.D..