Pre-clinical efficacy in multiple syngeneic models with oral immune checkpoint antagonists targeting PD-L1 and TIM-3

Sasikumar, Pottayil G.; Sudarshan, Naremaddepalli S.; Ramachandra, Raghuveer K.; Samiulla, Dodderi S.; Bilugudi, P.; Adurthi, Srinivas; Mani, Jiju; Nair, Rashmi; Gowda, Nagesh; Ramachandra, Murali

doi:10.1016/s0959-8049(16)32890-8

Cited by 3 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Small PD-L1 inhibitors developed by BMS can induce the PD-L1 dimer by filling a deep hydrophobic channel-like pocket between two PD-L1 molecules and then blocking PD-1 binding [8,9]. Oral molecule, CA-327, shows anti-tumor activity in preclinical cancer models by inhibiting the PD-L1 and T cell immunoglobulin domain and mucin domain-3 (TIM-3) [10].…”

Section: Mechanisms Of Small Molecule Drugsmentioning

confidence: 99%

Emerging immunological strategies: recent advances and future directions

et al. 2021

View full text Add to dashboard Cite

Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.

show abstract

Section: Mechanisms Of Small Molecule Drugsmentioning

confidence: 99%

Emerging immunological strategies: recent advances and future directions

et al. 2021

View full text Add to dashboard Cite

show abstract

Small-Molecule Immune Checkpoint Inhibitors Targeting PD-1/PD-L1 and Other Emerging Checkpoint Pathways

Sasikumar

Ramachandra

2018

BioDrugs

View full text Add to dashboard Cite

Advances in harnessing the immune system for cancer treatment have been spectacular in recent years as witnessed by the approval of a number of antibodies targeting the PD-1/PD-L1 immune checkpoint pathway spanning an expanding list of indications. However, it is well recognized that while these antibodies show impressive clinical activity, they suffer from shortcomings including the failure to show response in a majority of patients, their need to be administered by intravenous injection, and immune-related adverse events due to the breaking of immune self-tolerance. Small-molecule-based therapeutic approaches offer the potential to address the shortcomings of these antibody-based checkpoint inhibitors. In the first part of this review, we discuss the rationale for small-molecule-based checkpoint therapy followed by efforts on the discovery of small-molecule-based approaches targeting the PD-1/PD-L1 axis and other immune checkpoint pathways. In the latter part of the article, we describe small-molecule inhibitors simultaneously targeting two non-redundant checkpoint inhibitor pathways as an approach to improve the response rate. A brief review of the progress of an oral small-molecule checkpoint inhibitor currently in clinical development is presented at the end.

show abstract

Advance investigation on synthetic small-molecule inhibitors targeting PD-1/PD-L1 signaling pathway

Awadasseid

Zhang

2021

Life Sciences

View full text Add to dashboard Cite

Pre-clinical efficacy in multiple syngeneic models with oral immune checkpoint antagonists targeting PD-L1 and TIM-3

Cited by 3 publications

References 0 publications

Emerging immunological strategies: recent advances and future directions

Emerging immunological strategies: recent advances and future directions

Small-Molecule Immune Checkpoint Inhibitors Targeting PD-1/PD-L1 and Other Emerging Checkpoint Pathways

Advance investigation on synthetic small-molecule inhibitors targeting PD-1/PD-L1 signaling pathway

Contact Info

Product

Resources

About