Protein-Targeted Degradation Agents Based on Natural Products

Natural products are an important source of drug lead compounds, and natural products with significant biological activity are constantly being discovered and used in clinical practice. At present, natural products play an important role in the targeted therapy of cancer, cardiovascular and cerebrovascular diseases, nervous system diseases, and autoimmune diseases. Meanwhile, in recent years, the rise of protein-targeted degradation technologies, such as proteolysis-targeting chimeras (PROTACs) and molecular glues, has provided a new solution for drug resistance caused by clinical molecular-targeting drugs. It is noteworthy that natural products and their derivatives, as important components of PROTACs and molecular glues, play an important role in the development of protein-targeting drugs. Hence, this review summarized the protein-targeted degradation agents based on natural products, such as PROTACs and molecular glues. More natural products with the potential to be used in the development of PROTACs and molecular glues as targeted protein degradation agents are still being investigated.

[1]  Kewu Zeng,et al.  Atypical E3 ligase ZFP91 promotes small-molecule-induced E2F2 transcription factor degradation for cancer therapy , 2022, EBioMedicine.

[2]  Lihe Zhang,et al.  Discovery of Pentacyclic Triterpenoid PROTACs as a Class of Effective Hemagglutinin Protein Degraders. , 2022, Journal of medicinal chemistry.

[3]  Zhenlong Liu,et al.  An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA , 2022, Nature communications.

[4]  De-juan Sun,et al.  PROTAC technology as a novel tool to identify the target of lathyrane diterpenoids , 2022, Acta pharmaceutica Sinica. B.

[5]  Hening Lin,et al.  Attenuation of NLRP3 Inflammasome Activation by Indirubin-Derived PROTAC Targeting HDAC6. , 2021, ACS chemical biology.

[6]  Rachel M. Webster,et al.  The prostate cancer drug market , 2021, Nature Reviews Drug Discovery.

[7]  Wenyi Wei,et al.  Cancer Selective Target Degradation by Folate-Caged PROTACs. , 2021, Journal of the American Chemical Society.

[8]  Chengzhang Wang,et al.  Design and linkage optimization of ursane-thalidomide-based PROTACs and identification of their targeted-degradation properties to MDM2 protein. , 2021, Bioorganic chemistry.

[9]  Weiping Tang,et al.  Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries. , 2021, European journal of medicinal chemistry.

[10]  Harish C. Upadhyay.  Coumarin-1,2,3-triazole Hybrid Molecules: An Emerging Scaffold for Combating Drug Resistance. , 2021, Current topics in medicinal chemistry.

[11]  Lixia Chen,et al.  Rational Design and Synthesis of Novel Dual PROTACs for Simultaneous Degradation of EGFR and PARP. , 2021, Journal of medicinal chemistry.

[12]  Jin-jian Lu,et al.  Natural Products in Cancer Therapy: Past, Present and Future , 2021, Natural Products and Bioprospecting.

[13]  Guoshun Luo,et al.  Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity in vivo , 2020, Acta pharmaceutica Sinica. B.

[14]  Wei Zhu,et al.  Wogonin Ameliorates Renal Inflammation and Fibrosis by Inhibiting NF-κB and TGF-β1/Smad3 Signaling Pathways in Diabetic Nephropathy , 2020, Drug design, development and therapy.

[15]  Shaomeng Wang,et al.  A highly potent PROTAC androgen receptor (AR) degrader ARD-61 effectively inhibits AR-positive breast cancer cell growth in vitro and tumor growth in vivo , 2020, Neoplasia.

[16]  De-juan Sun,et al.  PROTACs: New method to degrade transcription regulating proteins. , 2020, European journal of medicinal chemistry.

[17]  C. Crews,et al.  PROTACs: An Emerging Therapeutic Modality in Precision Medicine. , 2020, Cell chemical biology.

[18]  Guoshun Luo,et al.  Targeting estrogen receptor α for degradation with PROTACs: A promising approach to overcome endocrine resistance. , 2020, European journal of medicinal chemistry.

[19]  Carolyn R. Bertozzi,et al.  Lysosome-targeting chimaeras for degradation of extracellular proteins , 2020, Nature.

[20]  Xiang Li,et al.  A PROTAC peptide induces durable β-catenin degradation and suppresses Wnt-dependent intestinal cancer , 2020, Cell Discovery.

[21]  N. Huang,et al.  Identification of PDE6D as a potential target of sorafenib via PROTAC technology , 2020, bioRxiv.

[22]  Jie Luo,et al.  Degradation Versus Inhibition: Development of Proteolysis-Targeting Chimeras for Overcoming Statin-Induced Compensatory Upregulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase. , 2020, Journal of medicinal chemistry.

[23]  M. Schirle,et al.  A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL , 2020, bioRxiv.

[24]  S. Schreiber,et al.  Unifying principles of bifunctional, proximity-inducing small molecules , 2020, Nature Chemical Biology.

[25]  U. Banerji,et al.  Exploiting the folate receptor α in oncology , 2020, Nature Reviews Clinical Oncology.

[26]  Shi-Yong Sun,et al.  A cell-permeable peptide-based PROTAC against the oncoprotein CREPT proficiently inhibits pancreatic cancer , 2020, Theranostics.

[27]  Shaomeng Wang,et al.  Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands. , 2019, Journal of medicinal chemistry.

[28]  John A. Tallarico,et al.  Manumycin Polyketides Act as Molecular Glues Between UBR7 and P53 , 2019, bioRxiv.

[29]  M. Naito,et al.  Development of small molecule chimeras that recruit AhR E3 ligase to target proteins. , 2019, ACS chemical biology.

[30]  Zhaomin Liu,et al.  Simple Structural Modifications Converting a Bona Fide MDM2 PROTAC Degrader into a Molecular Glue Molecule: A Cautionary Tale in the Design of PROTAC Degraders. , 2019, Journal of medicinal chemistry.

[31]  B. Druker,et al.  Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-mediated Targeted Protein Degradation. , 2019, Cancer research.

[32]  R. Sedrani,et al.  Derivation of Rapamycin: Adventures in Natural Product Chemistry. , 2019, Chimia.

[33]  Ryan P. Wurz,et al.  Targeted Degradation of MDM2 as a New Approach to Improve the Efficacy of MDM2-p53 Inhibitors. , 2019, Journal of medicinal chemistry.

[34]  Liu Liu,et al.  Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression. , 2018, Journal of medicinal chemistry.

[35]  C. Crews,et al.  MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53. , 2018, Cancer research.

[36]  Yajing Wang,et al.  Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity. , 2018, Bioorganic chemistry.

[37]  Jie Luo,et al.  Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol , 2018, Nature Communications.

[38]  Jian Min,et al.  New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons. , 2018, ACS medicinal chemistry letters.

[39]  Hui Zhao,et al.  Development of Stabilized Peptide-Based PROTACs against Estrogen Receptor α. , 2018, ACS chemical biology.

[40]  William E. Carson,et al.  Diffusion mapping of drug targets on disease signaling network elements reveals drug combination strategies , 2018, PSB.

[41]  Xi Xu,et al.  Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in vitro. , 2017, European journal of medicinal chemistry.

[42]  Y. Hashimoto,et al.  Discovery of Small Molecules that Induce the Degradation of Huntingtin. , 2017, Angewandte Chemie.

[43]  B. O'Neil,et al.  Targeted therapy for advanced gastric cancer: A review of current status and future prospects. , 2015, World journal of gastrointestinal oncology.

[44]  J. Mackey,et al.  CRABP1 is associated with a poor prognosis in breast cancer: adding to the complexity of breast cancer cell response to retinoic acid , 2015, Molecular Cancer.

[45]  Hong-min Liu,et al.  Spirooxindoles: Promising scaffolds for anticancer agents. , 2015, European journal of medicinal chemistry.

[46]  J. Deschamps,et al.  Design of Chemically Stable, Potent, and Efficacious MDM2 Inhibitors That Exploit the Retro-Mannich Ring-Opening-Cyclization Reaction Mechanism in Spiro-oxindoles , 2014, Journal of medicinal chemistry.

[47]  Cesare R Sirtori,et al.  The pharmacology of statins. , 2014, Pharmacological research.

[48]  G. Goss,et al.  Drug Resistance to Molecular Targeted Therapy and Its Consequences for Treatment Decisions in Non-Small-Cell Lung Cancer , 2014, Front. Oncol..

[49]  Yaroslav A. Kainov,et al.  Expression and clinical significance of CRABP1 and CRABP2 in non-small cell lung cancer , 2014, Tumor Biology.

[50]  D. Newman,et al.  Natural products as leads to antitumor drugs , 2014, Phytochemistry Reviews.

[51]  F. Khuri,et al.  Targeting protein-protein interactions as an anticancer strategy. , 2013, Trends in pharmacological sciences.

[52]  Nicholas H Oberlies,et al.  Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma , 2011, The Journal of Antibiotics.

[53]  E. Choi,et al.  Jostling for Position: Optimizing Linker Location in the Design of Estrogen Receptor‐Targeting PROTACs , 2010, ChemMedChem.

[54]  E. Choi,et al.  Targeted Degradation of the Aryl Hydrocarbon Receptor by the PROTAC Approach: A Useful Chemical Genetic Tool , 2007, Chembiochem : a European journal of chemical biology.

[55]  Michal Sharon,et al.  Mechanism of auxin perception by the TIR1 ubiquitin ligase , 2007, Nature.

[56]  D. Newman,et al.  Natural products as sources of new drugs over the last 25 years. , 2007, Journal of natural products.

[57]  H. Swanson,et al.  Identification of kaempferol as an inhibitor of cigarette smoke-induced activation of the aryl hydrocarbon receptor and cell transformation. , 2006, Carcinogenesis.

[58]  L. Chiang,et al.  Anti-proliferative effect of apigenin and its apoptotic induction in human Hep G2 cells. , 2006, Cancer letters.

[59]  E. Ariazi,et al.  Estrogen receptors as therapeutic targets in breast cancer. , 2006, Current topics in medicinal chemistry.

[60]  S. Baek,et al.  Use of PROTACS as molecular probes of angiogenesis. , 2005, Bioorganic & medicinal chemistry letters.

[61]  M. Estelle,et al.  The F-box protein TIR1 is an auxin receptor , 2005, Nature.

[62]  H. Stähelin,et al.  Immunosuppressive and specific antimitotic effects of ovalicin , 1968, Experientia.

[63]  Michael A. Koldobskiy,et al.  Chemical genetic control of protein levels: selective in vivo targeted degradation. , 2004, Journal of the American Chemical Society.

[64]  A. Ransick,et al.  Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation* , 2003, Molecular & Cellular Proteomics.

[65]  I. Pogribny,et al.  Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice. , 2002, Carcinogenesis.

[66]  I. Pongratz,et al.  Differential Usage of Nuclear Export Sequences Regulates Intracellular Localization of the Dioxin (Aryl Hydrocarbon) Receptor* , 2001, The Journal of Biological Chemistry.

[67]  R. Deshaies,et al.  Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Eric C. Griffith,et al.  Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2. , 1998, Proceedings of the National Academy of Sciences of the United States of America.