International Journal of Molecular Sciences

Editorial

Jump to: Research, Review

3 pages, 184 KiB

Open AccessEditorial

Editorial for the Special Issue—“Recent Advances of Novel Pharmaceutical Designs for Anti-Cancer Therapies”

by Bernhard Biersack

Int. J. Mol. Sci. 2023, 24(9), 8238; https://doi.org/10.3390/ijms24098238 - 5 May 2023

Viewed by 1232

Abstract

Cancer is one of the leading causes of death worldwide, despite the promising developments in terms of the curing and management of certain cancer types that have occurred over the last decades saving and prolonging the lives of numerous patients [...] Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

Research

Jump to: Editorial, Review

36 pages, 3477 KiB

Open AccessArticle

Molecular Docking and Dynamics Simulation Studies Predict Potential Anti-ADAR2 Inhibitors: Implications for the Treatment of Cancer, Neurological, Immunological and Infectious Diseases

by Emmanuel Broni, Andrew Striegel, Carolyn Ashley, Patrick O. Sakyi, Saqib Peracha, Miriam Velazquez, Kristeen Bebla, Monsheel Sodhi, Samuel K. Kwofie, Adesanya Ademokunwa, Sufia Khan and Whelton A. Miller III

Int. J. Mol. Sci. 2023, 24(7), 6795; https://doi.org/10.3390/ijms24076795 - 5 Apr 2023

Cited by 12 | Viewed by 4740

Abstract

Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders [...] Read more.

Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from −81.304 to −1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (−1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [−873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

19 pages, 3892 KiB

Open AccessArticle

Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer

by Sangita Bhattacharyya, Hindole Ghosh, Obdulia Covarrubias-Zambrano, Krishan Jain, K. Venkateswara Swamy, Anup Kasi, Ameer Hamza, Shrikant Anant, Michael VanSaun, Scott J. Weir, Stefan H. Bossmann, Subhash B. Padhye and Prasad Dandawate

Int. J. Mol. Sci. 2023, 24(7), 6336; https://doi.org/10.3390/ijms24076336 - 28 Mar 2023

Cited by 9 | Viewed by 2833

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the primary reason for cancer-related deaths in the US. Genetic mutations, drug resistance, the involvement of multiple signaling pathways, cancer stem cells (CSCs), and desmoplastic stroma, which hinders drug penetrance, contribute to poor chemotherapeutic efficacy. Hence, there is [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is the primary reason for cancer-related deaths in the US. Genetic mutations, drug resistance, the involvement of multiple signaling pathways, cancer stem cells (CSCs), and desmoplastic stroma, which hinders drug penetrance, contribute to poor chemotherapeutic efficacy. Hence, there is a need to identify novel drugs with improved delivery to improve treatment outcomes. Curcumin is one such compound that can inhibit multiple signaling pathways and CSCs. However, curcumin’s clinical applicability for treating PDAC is limited because of its poor solubility in water and metabolic instability. Hence, we developed a difluorinated curcumin (CDF) analog that accumulates selectively in the pancreas and inhibits PDAC growth in vitro and in vivo. In the present work, we developed its 2-hydroxy-propyl-β-cyclodextrin (HCD) inclusion complex to increase its water solubility and hydrolytic stability. The CDFHCD inclusion complex was characterized by spectroscopic, thermal, and microscopic techniques. The inclusion complex exhibited increased aqueous solubility, hydrolytic stability, and antiproliferative activity compared to parent CDF. Moreover, CDF and CDFHCD inhibited colony and spheroid formation, and induced cell cycle and apoptosis in PDAC cell lines. Hence, CDFHCD self-assembly is an efficient approach to increase water solubility and anticancer therapeutic efficacy, which now warrants advancement towards a clinical proof of concept in PDAC patients. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

24 pages, 5622 KiB

Open AccessArticle

Differential CMS-Related Expression of Cell Surface Carbonic Anhydrases IX and XII in Colorectal Cancer Models—Implications for Therapy

by Arne Rotermund, Sarah Brandt, Martin S. Staege, Jana Luetzkendorf, Lutz P. Mueller and Thomas Mueller

Int. J. Mol. Sci. 2023, 24(6), 5797; https://doi.org/10.3390/ijms24065797 - 18 Mar 2023

Cited by 4 | Viewed by 2186

Abstract

Tumor-associated carbonic anhydrases IX (CAIX) and XII (CAXII) have long been in the spotlight as potential new targets for anti-cancer therapy. Recently, CAIX/CAXII specific inhibitor SLC-0111 has passed clinical phase I study and showed differential response among patients with colorectal cancer (CRC). CRC [...] Read more.

Tumor-associated carbonic anhydrases IX (CAIX) and XII (CAXII) have long been in the spotlight as potential new targets for anti-cancer therapy. Recently, CAIX/CAXII specific inhibitor SLC-0111 has passed clinical phase I study and showed differential response among patients with colorectal cancer (CRC). CRC can be classified into four different consensus molecular subgroups (CMS) showing unique expression patterns and molecular traits. We questioned whether there is a CMS-related CAIX/CAXII expression pattern in CRC predicting response. As such, we analyzed transcriptomic data of tumor samples for CA9/CA12 expression using Cancertool. Protein expression pattern was examined in preclinical models comprising cell lines, spheroids and xenograft tumors representing the CMS groups. Impact of CAIX/CAXII knockdown and SLC-0111 treatment was investigated in 2D and 3D cell culture. The transcriptomic data revealed a characteristic CMS-related CA9/CA12 expression pattern with pronounced co-expression of both CAs as a typical feature of CMS3 tumors. Protein expression in spheroid- and xenograft tumor tissue clearly differed, ranging from close to none (CMS1) to strong CAIX/CAXII co-expression in CMS3 models (HT29, LS174T). Accordingly, response to SLC-0111 analyzed in the spheroid model ranged from no (CMS1) to clear (CMS3), with moderate in CMS2 and mixed in CMS4. Furthermore, SLC-0111 positively affected impact of single and combined chemotherapeutic treatment of CMS3 spheroids. In addition, combined CAIX/CAXII knockdown and more effective treatment with SLC-0111 reduced clonogenic survival of CMS3 modelling single cells. In conclusion, the preclinical data support the clinical approach of targeted CAIX/CAXII inhibition by showing linkage of expression with response and suggest that patients with CMS3-classified tumors would most benefit from such treatment. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

26 pages, 4433 KiB

Open AccessArticle

New 4,5-Diarylimidazol-2-ylidene–iodidogold(I) Complexes with High Activity against Esophageal Adenocarcinoma Cells

by Sebastian W. Schleser, Hindole Ghosh, Gerald Hörner, Jonathan Seib, Sangita Bhattacharyya, Birgit Weber, Rainer Schobert, Prasad Dandawate and Bernhard Biersack

Int. J. Mol. Sci. 2023, 24(6), 5738; https://doi.org/10.3390/ijms24065738 - 17 Mar 2023

Cited by 4 | Viewed by 2202

Abstract

Inspired by the vascular-disrupting agent combretastatin A-4 and recently published anticancer active N-heterocyclic carbene (NHC) complexes of Au(I), a series of new iodidogold(I)–NHC complexes was synthesized and characterized. The iodidogold(I) complexes were synthesized by a route involving van Leusen imidazole formation and [...] Read more.

Inspired by the vascular-disrupting agent combretastatin A-4 and recently published anticancer active N-heterocyclic carbene (NHC) complexes of Au(I), a series of new iodidogold(I)–NHC complexes was synthesized and characterized. The iodidogold(I) complexes were synthesized by a route involving van Leusen imidazole formation and N-alkylation, followed by complexation with Ag₂O, transmetalation with chloro(dimethylsulfide)gold(I) [Au(DMS)Cl], and anion exchange with KI. The target complexes were characterized by IR spectroscopy, ¹H and ¹³C NMR spectroscopy, and mass spectrometry. The structure of 6c was validated via single-crystal X-ray diffraction. A preliminary anticancer screening of the complexes using two esophageal adenocarcinoma cell lines showed promising nanomolar activities for certain iodidogold(I) complexes accompanied with apoptosis induction, as well as c-Myc and cyclin D1 suppression in esophageal adenocarcinoma cells treated with the most promising derivative 6b. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

19 pages, 28807 KiB

Open AccessArticle

eIF4A1 Is a Prognostic Marker and Actionable Target in Human Hepatocellular Carcinoma

by Sara M. Steinmann, Anabel Sánchez-Martín, Elisabeth Tanzer, Antonio Cigliano, Giovanni M. Pes, Maria M. Simile, Laurent Desaubry, Jose J.G. Marin, Matthias Evert and Diego F. Calvisi

Int. J. Mol. Sci. 2023, 24(3), 2055; https://doi.org/10.3390/ijms24032055 - 20 Jan 2023

Cited by 2 | Viewed by 2761

Abstract

Hepatocellular carcinoma (HCC) is a primary liver tumor with high lethality and increasing incidence worldwide. While tumor resection or liver transplantation is effective in the early stages of the disease, the therapeutic options for advanced HCC remain limited and the benefits are temporary. [...] Read more.

Hepatocellular carcinoma (HCC) is a primary liver tumor with high lethality and increasing incidence worldwide. While tumor resection or liver transplantation is effective in the early stages of the disease, the therapeutic options for advanced HCC remain limited and the benefits are temporary. Thus, novel therapeutic targets and more efficacious treatments against this deadly cancer are urgently needed. Here, we investigated the pathogenetic and therapeutic role of eukaryotic initiation factor 4A1 (eIF4A1) in this tumor type. We observed consistent eIF4A1 upregulation in HCC lesions compared with non-tumorous surrounding liver tissues. In addition, eIF4A1 levels were negatively correlated with the prognosis of HCC patients. In HCC lines, the exposure to various eIF4A inhibitors triggered a remarkable decline in proliferation and augmented apoptosis, paralleled by the inhibition of several oncogenic pathways. Significantly, anti-growth effects were achieved at nanomolar concentrations of the eIF4A1 inhibitors and were further increased by the simultaneous administration of the pan mTOR inhibitor, Rapalink-1. In conclusion, our results highlight the pathogenetic relevance of eIF4A1 in HCC and recommend further evaluation of the potential usefulness of pharmacological combinations based on eIF4A and mTOR inhibitors in treating this aggressive tumor. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

19 pages, 3412 KiB

Open AccessArticle

Pterostilbene-Mediated Inhibition of Cell Proliferation and Cell Death Induction in Amelanotic and Melanotic Melanoma

by Joanna Wawszczyk, Katarzyna Jesse and Małgorzata Kapral

Int. J. Mol. Sci. 2023, 24(2), 1115; https://doi.org/10.3390/ijms24021115 - 6 Jan 2023

Cited by 5 | Viewed by 2291

Abstract

Melanoma is one of the fastest-growing cancers worldwide. Treatment of advanced melanoma is very difficult; therefore, there is growing interest in the identification of new therapeutic agents. Pterostilbene is a natural stilbene that has been found to have several pharmacological activities. The aim [...] Read more.

Melanoma is one of the fastest-growing cancers worldwide. Treatment of advanced melanoma is very difficult; therefore, there is growing interest in the identification of new therapeutic agents. Pterostilbene is a natural stilbene that has been found to have several pharmacological activities. The aim of this study was to evaluate the influence of pterostilbene on the proliferation and apoptosis of human melanoma cells. Proliferation of pterostilbene-treated amelanotic (C32) and melanotic (A2058) melanoma cells was determined by BRDU assay. Flow cytometric analyses were used to determine cell cycle progression, and further molecular investigations were performed using real-time RT-qPCR. The expression of the p21 protein and the DNA fragmentation assay were determined by the ELISA method. The results revealed that pterostilbene reduced the proliferation of both amelanotic and melanotic melanoma cells. Pterostilbene induced apoptosis in amelanotic C32 melanoma cells, and this effect was mediated by an increase in the expression of the BAX, CASP9, and CASP9 genes; induction of caspase 3 activity; and DNA degradation. Pterostilbene did not affect the activation of apoptosis in the A2058 cell line. It may be concluded that pterostilbene has anticancer potential against human melanoma cells; however, more studies are still needed to fully elucidate the effects of pterostilbene on amelanotic and melanotic melanoma cells. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

16 pages, 6046 KiB

Open AccessArticle

Discovery of Simple Diacylhydrazine-Functionalized Cinnamic Acid Derivatives as Potential Microtubule Stabilizers

by Xiang Zhou, Yi-Hong Fu, Ya-Yu Zou, Jiao Meng, Gui-Ping Ou-Yang, Qiang-Sheng Ge and Zhen-Chao Wang

Int. J. Mol. Sci. 2022, 23(20), 12365; https://doi.org/10.3390/ijms232012365 - 15 Oct 2022

Cited by 8 | Viewed by 1860

Abstract

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. [...] Read more.

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. Notably, compound I₂₃ exhibited the best antiproliferative activity against three cancer lines with IC₅₀ values ranging from 3.36 to 5.99 μM and concurrently afforded a lower cytotoxicity towards the NRK-52E cells. Anticancer mechanism investigations suggested that the highly bioactive compound I₂₃ could potentially promote the protofilament assembly of tubulin, thus eventually leading to the stagnation of the G2/M phase cell cycle of HepG2 cells. Moreover, compound I₂₃ also disrupted cancer cell migration and significantly induced HepG2 cells apoptosis in a dosage-dependent manner. Additionally, the in silico analysis indicated that compound I₂₃ exhibited an acceptable pharmacokinetic profile. Overall, these easily prepared N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives could serve as potential microtubule-interacting agents, probably as novel microtubule-stabilizers. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

16 pages, 6543 KiB

Open AccessArticle

Antitumor Effects of a New Retinoate of the Fungal Cytotoxin Illudin M in Brain Tumor Models

by Benedikt Linder, Miroslava Zoldakova, Zsuzsanna Kornyei, Leonhard H. F. Köhler, Sebastian Seibt, Dominic Menger, André Wetzel, Emília Madarász, Rainer Schobert, Donat Kögel and Bernhard Biersack

Int. J. Mol. Sci. 2022, 23(16), 9056; https://doi.org/10.3390/ijms23169056 - 13 Aug 2022

Cited by 3 | Viewed by 2057

Abstract

While the fungal metabolite illudin M (1) is indiscriminately cytotoxic in cancer and non-malignant cells, its retinoate 2 showed a greater selectivity for the former, especially in a cerebral context. Illudin M killed malignant glioma cells as well as primary neurons [...] Read more.

While the fungal metabolite illudin M (1) is indiscriminately cytotoxic in cancer and non-malignant cells, its retinoate 2 showed a greater selectivity for the former, especially in a cerebral context. Illudin M killed malignant glioma cells as well as primary neurons and astrocytes at similarly low concentrations and destroyed their microtubule and glial fibrillary acidic protein (GFAP) networks. In contrast, the ester 2 was distinctly more cytotoxic in highly dedifferentiated U87 glioma cells than in neurons, which were even stimulated to enhanced growth. This was also observed in co-cultures of neurons with U87 cells where conjugate 2 eventually killed them by induction of differentiation based on the activation of nuclear receptors, which bind to retinoid-responsive elements (RARE). Hence, illudin M retinoate 2 appears to be a promising drug candidate. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

18 pages, 2056 KiB

Open AccessReview

Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art

by Han Zhang, Jiayou Cai, Siqi Yu, Bin Sun and Weicheng Zhang

Int. J. Mol. Sci. 2023, 24(6), 5184; https://doi.org/10.3390/ijms24065184 - 8 Mar 2023

Cited by 6 | Viewed by 3103

Abstract

Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by [...] Read more.

Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by a wide assortment of small molecules with excellent anticancer activity, among which plitidepsin has been granted approval for the treatment of multiple myeloma. Meanwhile, metarrestin is currently under clinical development for metastatic cancers. Bearing these exciting advances in mind, it would be desirable to present a systematic up-to-date account of the title topic, which, to the best of our knowledge, has thus far been unavailable in the literature. The present review summarizes recent advances in eEF1A-targeting anticancer agents, both naturally occurring and synthetically crafted, with regard to their discovery or design, target identification, structure–activity relationship, and mode of action. Their structural diversity and differential eEF1A-targeting mechanisms warrant continuing research in pursuit of curing eEF1A-driven malignancy. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

27 pages, 1688 KiB

Open AccessReview

Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents

by Bianca Nitzsche, Michael Höpfner and Bernhard Biersack

Int. J. Mol. Sci. 2023, 24(4), 4083; https://doi.org/10.3390/ijms24044083 - 17 Feb 2023

Cited by 9 | Viewed by 2993

Abstract

A class of chaperones dubbed heat shock protein 70 (Hsp70) possesses high relevance in cancer diseases due to its cooperative activity with the well-established anticancer target Hsp90. However, Hsp70 is closely connected with a smaller heat shock protein, Hsp40, forming a formidable Hsp70-Hsp40 [...] Read more.

A class of chaperones dubbed heat shock protein 70 (Hsp70) possesses high relevance in cancer diseases due to its cooperative activity with the well-established anticancer target Hsp90. However, Hsp70 is closely connected with a smaller heat shock protein, Hsp40, forming a formidable Hsp70-Hsp40 axis in various cancers, which serves as a suitable target for anticancer drug design. This review summarizes the current state and the recent developments in the field of (semi-)synthetic small molecule inhibitors directed against Hsp70 and Hsp40. The medicinal chemistry and anticancer potential of pertinent inhibitors are discussed. Since Hsp90 inhibitors have entered clinical trials but have exhibited severe adverse effects and drug resistance formation, potent Hsp70 and Hsp40 inhibitors may play a significant role in overcoming the drawbacks of Hsp90 inhibitors and other approved anticancer drugs. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Graphical abstract

32 pages, 52211 KiB

Open AccessReview

Recent Advances in PROTACs for Drug Targeted Protein Research

by Tingting Yao, Heng Xiao, Hong Wang and Xiaowei Xu

Int. J. Mol. Sci. 2022, 23(18), 10328; https://doi.org/10.3390/ijms231810328 - 7 Sep 2022

Cited by 34 | Viewed by 8576

Abstract

Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is [...] Read more.

Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is performed through the ubiquitin–proteasome system (UPS). The general process is that PROTAC binds to the target protein and E3 ligase to form a ternary complex and label the target protein with ubiquitination. The ubiquitinated protein is recognized and degraded by the proteasome in the cell. At present, PROTAC, as a new type of drug, has been developed to degrade a variety of cancer target proteins and other disease target proteins, and has shown good curative effects on a variety of diseases. For example, PROTACs targeting AR, BR, BTK, Tau, IRAK4, and other proteins have shown unprecedented clinical efficacy in cancers, neurodegenerative diseases, inflammations, and other fields. Recently, PROTAC has entered a phase of rapid development, opening a new field for biomedical research and development. This paper reviews the various fields of targeted protein degradation by PROTAC in recent years and summarizes and prospects the hot targets and indications of PROTAC. Full article

(This article belongs to the Special Issue Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Recent Advances of Novel Pharmaceutical Designs for Anti-cancer Therapies

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (12 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI