Small molecules as antagonists of co-inhibitory pathways for cancer immunotherapy: a patent review (2018-2019)

Blockade of PD-1/PD-L1 interactions using PD-1/PD-L1 pathway modulators has shown unprecedented clinical efficacy in various cancer models. Current PD-1/PD-L1 modulators approved by FDA are exclusively dominated by therapeutic antibodies. Nevertheless, therapeutic antibodies also exhibit several disadvantages such as low tumor penetration, difficulty in crossing physiological barriers, lacking oral bioavailability, high manufacturing costs, inaccessible to intracellular targets, immunogenicity, immune-related adverse events (irAEs). Modulation of PD-1/PD-L1 pathway using small molecules may be an alternative approach to mobilize immune system to fight against cancers. In this review, we focus on summarizing the recently disclosed chemical structures and preliminary structure-activity relationships (SARs) of small molecules as PD-1/PD-L1 modulators for cancer immunotherapy.

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Searching for effective antiviral small molecules against influenza A virus: A patent review

Expert Opinion on Therapeutic Patents ◽

10.1080/13543776.2020.1831471 ◽

2020 ◽

pp. 1-14

Author(s):

Tiziana Ginex ◽

F. Javier Luque

Keyword(s):

Small Molecules ◽

Influenza A Virus ◽

Influenza A ◽

Patent Review

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A patent review on PD-1/PD-L1 antagonists: small molecules, peptides, and macrocycles (2015-2018)

Expert Opinion on Therapeutic Patents ◽

10.1080/13543776.2018.1512706 ◽

2018 ◽

Vol 28 (9) ◽

pp. 665-678 ◽

Cited By ~ 40

Author(s):

Shabnam Shaabani ◽

Harmen P.S. Huizinga ◽

Roberto Butera ◽

Ariana Kouchi ◽

Katarzyna Guzik ◽

...

Keyword(s):

Small Molecules ◽

Patent Review

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Co-stimulatory and co-inhibitory pathways in cancer immunotherapy

Advances in Cancer Research - Immunotherapy of Cancer ◽

10.1016/bs.acr.2019.03.003 ◽

2019 ◽

pp. 145-194 ◽

Cited By ~ 1

Author(s):

Rachel E. O’Neill ◽

Xuefang Cao

Keyword(s):

Cancer Immunotherapy ◽

Inhibitory Pathways

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Opportunities for Small Molecules in Cancer Immunotherapy

Trends in Immunology ◽

10.1016/j.it.2020.04.004 ◽

2020 ◽

Vol 41 (6) ◽

pp. 493-511 ◽

Cited By ~ 5

Author(s):

Sabina Y. van der Zanden ◽

Jolien J. Luimstra ◽

Jacques Neefjes ◽

Jannie Borst ◽

Huib Ovaa

Keyword(s):

Small Molecules ◽

Cancer Immunotherapy

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Discovery of IDO1 and DNA dual targeting antitumor agents

Organic & Biomolecular Chemistry ◽

10.1039/c7ob02529g ◽

2017 ◽

Vol 15 (47) ◽

pp. 9992-9995 ◽

Cited By ~ 4

Author(s):

Kun Fang ◽

Shanchao Wu ◽

Guoqiang Dong ◽

Ying Wu ◽

Shuqiang Chen ◽

...

Keyword(s):

Small Molecules ◽

Cancer Immunotherapy ◽

Antitumor Agents ◽

Indoleamine 2,3 Dioxygenase ◽

Dual Targeting ◽

Promising Target

The development of small molecules for cancer immunotherapy is highly challenging and indoleamine 2,3-dioxygenase 1 (IDO1) represents a promising target.

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Small molecule targeting of SHIP1 and SHIP2

Biochemical Society Transactions ◽

10.1042/bst20190775 ◽

2020 ◽

Vol 48 (1) ◽

pp. 291-300 ◽

Cited By ~ 2

Author(s):

William G. Kerr ◽

Chiara Pedicone ◽

Shawn Dormann ◽

Angela Pacherille ◽

John D. Chisholm

Keyword(s):

Cell Signaling ◽

Small Molecules ◽

Cancer Immunotherapy ◽

Phosphatase Activity ◽

Small Molecule ◽

Pi3k Pathway ◽

Disease States ◽

Src Homology 2 ◽

Src Homology ◽

Unconventional Method

Modulating the activity of the Src Homology 2 (SH2) — containing Inositol 5′-Phosphatase (SHIP) enzyme family with small molecule inhibitors provides a useful and unconventional method of influencing cell signaling in the PI3K pathway. The development of small molecules that selectively target one of the SHIP paralogs (SHIP1 or SHIP2) as well as inhibitors that simultaneously target both enzymes have provided promising data linking the phosphatase activity of the SHIP enzymes to disorders and disease states that are in dire need of new therapeutic targets. These include cancer, immunotherapy, diabetes, obesity, and Alzheimer's disease. In this mini-review, we will provide a brief overview of research in these areas that support targeting SHIP1, SHIP2 or both enzymes for therapeutic purposes.

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