The development of small-molecule inhibitors targeting CD47

Yu, Wei-Bang; Ye, Zi-Han; Chen, Xiuping; Shi, Jinqiao; Lu, Jin‐Jian

doi:10.1016/j.drudis.2020.11.003

Cited by 53 publications

(36 citation statements)

References 85 publications

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“…Both Pep-20 and RRx-001 are such small compounds that, when administered, disrupt the CD47-SIRP axis with minimal systemic toxicity ( 85 , 86 ). More small molecules are likely to be discovered as a result of optimized high throughput screenings for the discovery of new CD47-SIRPα inhibitors ( 87 , 88 ).…”

Section: Cd47-sirpα Axismentioning

confidence: 99%

Targeting Myeloid Checkpoint Molecules in Combination With Antibody Therapy: A Novel Anti-Cancer Strategy With IgA Antibodies?

et al. 2022

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Immunotherapy with therapeutic antibodies has shown a lack of durable responses in some patients due to resistance mechanisms. Checkpoint molecules expressed by tumor cells have a deleterious impact on clinical responses to therapeutic antibodies. Myeloid checkpoints, which negatively regulate macrophage and neutrophil anti-tumor responses, are a novel type of checkpoint molecule. Myeloid checkpoint inhibition is currently being studied in combination with IgG-based immunotherapy. In contrast, the combination with IgA-based treatment has received minimal attention. IgA antibodies have been demonstrated to more effectively attract and activate neutrophils than their IgG counterparts. Therefore, myeloid checkpoint inhibition could be an interesting addition to IgA treatment and has the potential to significantly enhance IgA therapy.

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Section: Cd47-sirpα Axismentioning

confidence: 99%

Targeting Myeloid Checkpoint Molecules in Combination With Antibody Therapy: A Novel Anti-Cancer Strategy With IgA Antibodies?

et al. 2022

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“…Therapeutic approaches currently focus on inhibiting the CD47-SIRPa binding to activate phagocytosis of cancer cells and several small and large molecule inhibitors are undergoing clinical investigations. Small molecule inhibitors are currently in preclinical stage only and have been recently reviewed elsewhere [ 117 ]. Table 5 gives an overview of large molecule CD47 inhibitors in early clinical trials.…”

Section: Immunological Based Therapies In Hccmentioning

confidence: 99%

Immunmodulatory Treatment Strategies of Hepatocellular Carcinoma: From Checkpoint Inhibitors Now to an Integrated Approach in the Future

Ocker

Mayr

Kiesslich

et al. 2021

Cancers

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Background: Hepatocellular carcinoma (HCC) still represents a human tumor entity with very limited therapeutic options, especially for advanced stages. Here, immune checkpoint modulating drugs alone or in combination with local ablative techniques could open a new and attractive therapeutic “door” to improve outcome and response rate for patients with HCC. Methods: Published data on HCC experimental to pre-(clinical) treatment strategies from standard of care to novel immunomodulatory concepts were summarized and discussed in detail. Results: Overall, our knowledge of the role of immune checkpoints in HCC is dramatically increased in the last years. Experimental and pre-clinical findings could be translated to phase 1 and 2 clinical trials and became standard of care. Local ablative techniques of HCC could improve the effectivity of immune checkpoint inhibitors in situ. Conclusions: This review demonstrates the importance of immunomodulatory treatment strategies of HCC, whereby the “best treatment code” of immune checkpoint drugs, combination with ablative techniques and of timing must be evaluated in coming clinical trials.

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“…The development of immune checkpoint inhibitors (ICIs) targeting the adaptive immune system, such as programmed cell death protein-1 (PD-1) and its ligand PD-L1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), has improved outcomes in patients with advanced metastatic breast cancer and triple-negative breast cancer (TNBC) (6,7). Although ICIs monotherapy can enhance T cell-mediated immunity, the overall response rate (ORR) is generally less than 30% (7)(8)(9)(10)(11). The inhibition of immune checkpoints targeting the innate immune system offers a new solution.…”

Section: Introductionmentioning

confidence: 99%

Targeting CD47 as a Novel Immunotherapy for Breast Cancer

et al. 2022

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Nowadays, breast cancer has become the most common cancer worldwide with a high mortality rate. Immune checkpoint blockade holds great promise in tumor‐targeted therapy, and CD47 blockade as one immune therapy is undergoing various preclinical studies and clinical trials to demonstrate its safety and efficacy in breast cancer. In this review, we summarized different therapeutic mechanisms targeting CD47 and its prognostic role and therapeutic value in breast cancer.

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The development of small-molecule inhibitors targeting CD47

Cited by 53 publications

References 85 publications

Targeting Myeloid Checkpoint Molecules in Combination With Antibody Therapy: A Novel Anti-Cancer Strategy With IgA Antibodies?

Targeting Myeloid Checkpoint Molecules in Combination With Antibody Therapy: A Novel Anti-Cancer Strategy With IgA Antibodies?

Immunmodulatory Treatment Strategies of Hepatocellular Carcinoma: From Checkpoint Inhibitors Now to an Integrated Approach in the Future

Targeting CD47 as a Novel Immunotherapy for Breast Cancer

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