BMS-202 / BMS - LARVOL DELTA

Evaluation of small molecule PD-1/PD-L1 inhibitors in a T cell reporter system. (PubMed, Biochem Pharmacol) - "We found that ARB-272572, INCB086550, Evixapodlin, and PD-1/PD-L1 Inhibitor 3 completely reversed the inhibitory effects of PD-1...AUNP-12, BMS1, BMS202, CA170, and PD-1/PD-L1-IN-9 were ineffective at reducing PD-1-mediated reporter inhibition. Moreover, our data indicate that adverse effects on T cell reporter activation compromise the activity of several of the tested compounds. In summary, our results revealed that the majority of small molecule PD-1/PD-L1 blockers possess a limited capacity to reverse PD-1 inhibition in a T cell reporter platform and highlight the importance of cellular assays to assess the therapeutic potential of drugs targeting the PD-1/PD-L1 axis."

Journal • Oncology

Intracellular Localization of PD-L1 in Rab10-positive Open Tubular Endosome System of Cancer Cells. (PubMed, Acta Histochem Cytochem) - "We also found that PD-L1 dimerized by the PD-L1 inhibitor BMS-202 was removed from the cell surface and Rab10-positive tubular endosomes and transported to the lysosomal degradation system. Taken together, this study provides novel insights that the Rab10-dependent tubular endocytic pathway may play an important role in the intracellular reservoir and recycling of PD-L1 to the surface of cancer cells, possibly regulating the amount of PD-L1 on the cell surface."

Journal • Oncology • PD-1 • PD-L1 • RAB10

Novel Resorcinol Dibenzyl Ether-Based PD-L1 Inhibitors Modulate Lipid Metabolism for Enhanced Tumor Immunotherapy. (PubMed, J Med Chem) - "Among these, compound ZQ8 exhibited the highest PD-L1 inhibitory activity (IC50 = 6.9 nM), significantly surpassing the reference compounds NP19 and BMS-202...In vivo studies using a HEPA1-6 mouse tumor model revealed that ZQ8 achieved 86.2% tumor growth inhibition at 20 mg/kg, accompanied by enhanced CD3+CD8+ T-cell infiltration and reduced lipid accumulation in serum. Collectively, ZQ8 represents a promising PD-1/PD-L1 inhibitor with immune- and lipid metabolism-modulating effects, warranting further study as a potential anticancer agent."

Journal • Metabolic Disorders • Oncology • CD8

Enrichment of ?d T cell capability for metastatic therapy by ex vivo ?activation and nanomedicine application (ESGO 2026) - "Nanodiamonds ‎were then functionalised with the PD-L1 inhibitor BMS202 to form nanocomplexes...This platform represents a ‎promising strategy to overcome the current limitations of immunotherapy in OC, ‎offering a potential single-dose therapeutic regimen that could improve treatment and patient outcomes. Further investigation is warranted to advance this platform toward clinical translation.‎"

IO biomarker • Metastases • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • CASP3 • GZMB • H2AX

Oxygen-carrying nanovaccine potentiates cancer immunotherapy for heterogeneous solid tumors. (PubMed, Mater Today Bio) - "BMS 202, a programmed cell death 1/programmed cell death 1 Ligand 1 (PD-L1) inhibitor, was loaded yielding 2P@Lipo-BMS-NBs-O2, which was found to reduce the expression levels hypoxia-inducible factor-1α and PD-L1, synergistically enhanced the pharmacodynamics of BMS 202, meanwhile, enhanced cytotoxic T-cell infiltration...Further incorporation of a fused cytomembrane (FM) from dendritic and B16F10 cells produced FM-2P@Lipo-BMS-NBs-O2, which exhibited superior heterogeneous tumor growth suppression, reduced stemness gene expression, increased CD8+ T-cell infiltration, and elevated IFN-γ levels in serum. Oxygen-carrying nanovaccine possess the features of oxygen delivery, T cell redirection and FM coating, represents full activation of T-cell function and a potent reduction of tumor stemness, offering a promising strategy for the treatment of highly heterogeneous solid tumors."

Heterogeneity • IO biomarker • Journal • Oncology • Solid Tumor • CD8 • EGFR • HIF1A • IFNG

ROS-responsive multifunctional DCS-based micelle hydrogel for simultaneously inhibiting post-resection melanoma recurrence and promoting wound healing. (PubMed, Nanoscale) - "In this study, a multifunctional micelle hydrogel (AB@MH) was fabricated by integrating reactive oxygen species (ROS)-responsive nanomicelles, which was co-loaded with apigenin and BMS-202, into a dodecyl-modified chitosan (DCS)-based hydrogel via Schiff base linkages and hydrogen bonding interactions for post-resection melanoma therapy...In the melanoma resection model, the AB@MH group markedly suppressed tumor recurrence and accelerated wound repair. This work successfully integrates post-resection antitumor therapy and wound healing enhancement, achieving both safety and efficacy in postoperative cancer therapy."

Journal • Melanoma • Oncology • Solid Tumor

Synthesis and Anti-Tumor Evaluation of Carboranyl BMS-202 Analogues-A Case of Carborane Not as Phenyl Ring Mimetic. (PubMed, Molecules) - "Further studies indicate that compound 1a can induce cell apoptosis and lead to G1 cell cycle phase arrest. The boron biodistribution study of compound 1a revealed that the brain/blood uptake ratio was 0.60 ± 0.08, exhibiting a good blood-brain penetration capability."

Journal • Oncology

Targeting PD-L1 with BMS-202 Enhances Antitumor Cytokine and Cytotoxic T-Lymphocyte Responses in C57BLx/6 Mouse Lung Carcinogenesis. (PubMed, Cancer Manag Res) - "Additionally, BMS-202 treatment significantly elevated levels of pro-inflammatory cytokines, including IFN-γ and TNF-α, indicating a robust immune response (P<0.001). These findings suggest that BMS-202 effectively promotes apoptosis and enhances immune responses in lung cancer, underscoring its potential as a therapeutic agent in treating lung carcinogenesis."

IO biomarker • Journal • Preclinical • Immune Modulation • Immunology • Lung Cancer • Oncology • Solid Tumor • ANXA5 • APAF1 • BAX • BCL2 • BCL2L1 • CASP3 • CD8 • IFNG • PD-1 • TNFA

Molecular dynamics reveals novel small-molecule inhibitors block PD-1/PD-L1 by promoting PD-L1 dimer stability. (PubMed, Phys Chem Chem Phys) - "Based on the lead compound BMS-202, this study systematically elucidated the dynamic binding mechanisms of three novel inhibitors (BMS-202, LP23, A56) with the PD-L1 dimer through molecular dynamics simulations and multifaceted analysis...Further analyses through dynamic cross-correlation matrix (DCCM) and principal component analysis (PCA) confirmed the highest structural rigidity and substantial correlated motions in the A56/PD-L1 complex, suggesting that A56 may achieve blockade of immune checkpoint signaling by stabilizing the closed conformation of the PD-L1 dimer and thereby dynamically occluding the PD-1/PD-L1 interaction interface. These findings elucidated the different binding mechanisms of novel small-molecule inhibitors to PD-L1 from both energy and conformational perspectives, providing a potential structural basis for the optimized design of immune checkpoint inhibitors."

Journal • Oncology

DRUG SCREENING IDENTIFIES BMS-202, COG1410, AND FINGOLIMOD AS BBBPENETRANT COMPOUNDS WITH ANTITUMOR ACTIVITY IN GLIOBLASTOMA CELL LINES (SIOP 2025) - "These findings highlight the therapeutic potential of these drugs for glioblastoma treatment, overcoming traditional barriers and resistance mechanisms. Funding: FAPESP (Grant: 2022/09037-3), INCT BioOncoPed-CNPq (Grant: 406484/2022-8)."

IO biomarker • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • ABCC1 • APOE • NOS1

Nebulized Inhalation of Engineered Extracellular Vesicles to Destruct Pre-metastatic Niche and Inhibit Postoperative Lung Metastasis in a Mouse Model. (PubMed, ACS Nano) - "Herein, M1 macrophage-derived, CXCR4-overexpressed, and BMS202-loaded extracellular vesicles (BMS@C-M1 EV) were constructed to inhibit postoperative melanoma lung metastasis...Therefore, BMS@C-M1 EV through nebulized inhalation could disrupt PMN formation and eliminate CTCs in the lung, effectively suppressing postoperative melanoma lung metastasis. This therapeutic approach holds great potential for preventing postoperative melanoma lung metastasis."

Journal • Preclinical • Immunology • Melanoma • Oncology • Solid Tumor • CTCs • CXCL12 • CXCR4

MOF-Mediated Aloe-Emodin Delivery Enhances Hepatocellular Carcinoma Immunotherapy via Pyroptosis and Immunosuppressant Synergy. (PubMed, Int J Nanomedicine) - "Combined with BMS-202, we explored suppression of the PD-1/PD-L1 complex and synergistic induction of pyroptosis...The synergistic approach of pyroptosis combined with an enhanced immunotherapy nanoplatform shows promise as an effective HCC immunotherapy strategy, with significant clinical translation potential. Future studies will optimize the platform and conduct clinical trials."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • PD-1 • PD-L1

In Situ Formed Nanocomposite Hydrogel Improve Local Delivery of Antiangiogenic Agents and Immune Checkpoint Inhibitor for Cervical Carcinoma Therapy. (PubMed, Adv Healthc Mater) - "To address these challenges, a nanocomposite hydrogel system (Apa/BPNPs@Gel) is developed by encapsulating PD-L1 inhibitor BMS202 nanoparticles coated with polyvinyl alcohol (BPNPs) into a polyvinyl alcohol/alginate hybrid hydrogel...Initially, the antiangiogenic agent apatinib (Apa) is released to alleviate tumor hypoxia through vascular normalization and enhance PD-L1 suppression, priming the TME for subsequent anti-PD(L)1 therapy...Notably, in preclinical cervical carcinoma models, Apa/BPNPs@Gel mediated combination therapy significantly inhibited tumor growth and prolonged survival by activating tumor-suppressed CD8+ T cells. Hence, this locally administrable hydrogel offers a versatile platform to modulate the immunosuppressive TME and enhance immunotherapeutic outcomes."

Checkpoint inhibition • Journal • Addiction (Opioid and Alcohol) • Cervical Cancer • Oncology • Solid Tumor • CD8

In vivo modulation of the tumor microenvironment: anti-tumor effects of combination therapy of fucoidan and small molecule immune checkpoint inhibitor BMS-202. (PubMed, Int Immunopharmacol) - "Additionally, immune profiling of the tumor tissue using IHC revealed an increased CD8+/FOXP3+ ratio and a reduced CD4+/CD8+ ratio, suggesting an immunomodulatory effect. In conclusion, fucoidan demonstrated the potential to enhance the anti-tumor efficacy of BMS-202 via modulation of the immune TME and downregulating key oncogenic pathways, warranting further investigation into its role in combination with immunotherapy."

Checkpoint inhibition • Journal • Preclinical • Oncology • Solid Tumor • CASP3 • CD4 • FOXP3 • IL6 • TGFB1

Direct effects of the small molecule PD‑L1 inhibitor BMS‑202 on A375 melanoma cells: Anti‑tumor activity accompanied by increased mitochondrial function. (PubMed, Mol Med Rep) - "By inhibiting mitochondrial function, the antitumor effects of BMS‑202 can be enhanced. Overall, the present study provides information on the potential antitumor mechanisms of BMS‑202 as well as a theoretical basis for its application in melanoma therapy."

Journal • Melanoma • Oncology • Solid Tumor • BAX • BCL2 • CASP3

Discovery of Small Molecule PD-L1 Inhibitors via Optimization of Solvent-Interaction Region for Cancer Immunotherapy. (PubMed, Chem Biol Drug Des) - "Among them, compound GJ19 showed the most potent anti-PD-L1 effects with an IC50 of 32.06 nM in the HTRF (homogenous time-resolved fluorescence) assay, better than BMS-202 (IC50 = 62.1 nM)...In the in vivo efficacy studies, GJ19 (intraperitoneal injection, 15 mg/kg) effectively suppressed tumor growth with a TGI of 56.8% in a B16-F10 melanoma mouse model by activating antitumor immunity. In conclusion, GJ19 represents a potential small molecule inhibitor of PD-L1, deserving further investigation for tumor immunotherapy."

Journal • Melanoma • Oncology • Solid Tumor

A DNA-Mediated Lysosomal Degradation Strategy for Targeted Degradation of PD-L1 Protein. (PubMed, J Med Chem) - "By employing click chemistry to conjugate the PD-L1 inhibitor BMS-202 with dendritic DNA scaffolds, we created a bifunctional compound, PBL1, which is capable of simultaneously targeting both SRs and PD-L1...The efficacy and specificity of PBL1 have been validated in A549 cells and zebrafish models. The development of this SRs-mediated lysosomal degradation strategy offers a promising new approach for cancer immunotherapy, providing a safer and more targeted alternative to existing PD-L1 inhibitors."

IO biomarker • Journal • Oncology

Discovery of (E)-2-cyano-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)-3-(1H-indol-3-yl)acrylamide as a novel TDO inhibitor for cancer treatment. (PubMed, Bioorg Chem) - "Notably, 5c synergized with the PD-1/PD-L1 inhibitor BMS-202, both in vitro and in vivo. These findings suggested compound 5c could serve as a promising candidate for targeting TDO to address tumor immune tolerance in cancer therapy."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor

An artificial-enzyme-equipped immunoregulator blocks platelet-mediated breast cancer hematogenous metastasis. (PubMed, Biomaterials) - "Concurrently, the disintegration of the nanoenzyme GSNO@B releases the immune checkpoint inhibitor BMS-202, further facilitating the immune clearance of CTCs. Therefore, through a three-step strategy, GSNO@B effectively suppresses primary tumors growth and metastatic tumors formation by blocking the platelet-mediated hematogenous tumor metastasis pathway."

Journal • Breast Cancer • Oncology • Solid Tumor • CTCs

Spatial transcriptomics reveals tumor microenvironment heterogeneity in EBV positive diffuse large B cell lymphoma. (PubMed, Sci Rep) - "Functional validation using the PD-1/PD-L1 inhibitor BMS202 revealed dose-dependent suppression of proliferation and enhanced apoptosis in EBV+Farage cells, with TLR4 emerging as a downstream effector showing EBV-status-dependent regulation. These findings not only link TME-driven PD-1/PD-L1 activation to EBV+DLBCL's poor prognosis but also provide preclinical evidence for PD-1/PD-L1 blockade as a therapeutic strategy."

Biomarker • Heterogeneity • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TLR4

Aging Exacerbates Checkpoint Inhibitor Pathway Dysfunction In Pulmonary Fibrosis (IMMUNOLOGY 2025) - "Treatment of fibrotic aged mice with a PD-1/PD-L1 inhibitor (BMS-202) resulted in significantly reduced mortality along with decreases in BAL Sircol and improved static lung compliance. These findings suggests that aged mice exhibit a more severe fibrotic phenotype accompanied by alterations in re-programmed AT2 cell numbers and enhanced PD-1/PD-L1 synapses. We propose a model wherein pro-fibrotic epithelial populations escape immune surveillance avoiding clearance by CD8+PD1+ T cells to promote a fibrogenic niche.Keywords: Animals Rodent; Cells T Cells; Molecules Cell Surface Molecules; Techniques/Approaches Transgenic/Knockout Mice; Tissues Lung"

Checkpoint inhibition • IO biomarker • Fibrosis • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • CCL2 • CD8 • TNFA

A surface plasmon resonance-based screening platform to identify potential PD-1/PD-L1 inhibitors from a FDA-approved drugs library for cancer immunotherapy (AACR 2025) - "Three compounds, RB, MB, and VP, were identified as hits, showing PD-1/PD-L1 blockade rates of 13.1%, 9.6%, and 6.7%, respectively, compared to the positive controls BMS-1166 (33%) and BMS-202 (8.4%)...Functional assays using a co-culture model of T cells and cancer cells, designed to replicate the tumor microenvironment, showed that RB treatment modulated IL-2 secretion and induced apoptosis in A375 cancer cells. Proteomic analysis of sorted Jurkat T cells from the co-culture model via bottom-up proteomics revealed key proteins and signaling pathways regulated by RB.Overall, these findings suggest that RB exerts significant PD-1/PD-L1 inhibitory activity and may hold promise as a repurposed drug candidate for cancer immunotherapy.Keywords: PD-1/PD-L1, FDA-approved drugs, surface plasmon resonance, STD-NMR, co-culture model, proteomics"

IO biomarker • Melanoma • Oncology • Solid Tumor

Catalytic Intermolecular Asymmetric [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes: Practical Synthesis of Enantioenriched Highly Substituted Bicyclo[2.1.1]hexanes. (PubMed, J Am Chem Soc) - "The resulting BCHs hold significant potential as benzene bioisosteres in the synthesis of chiral BCHex-Sonidegib and BCHex-BMS-202, mimicking the anticancer drug Sonidegib and the PD-1/PD-L1 inhibitor BMS-202, respectively. The outcome highlights the positive impact of bioisosteric replacement on physicochemical properties, while maintaining comparable antitumor activity to their aryl-containing counterparts."

Journal • Oncology

Metabolizable alloy clusters assemble nanoinhibitor for enhanced radiotherapy of tumor by hypoxia alleviation and intracellular PD-L1 restraint. (PubMed, J Nanobiotechnology) - "In conclusion, the therapeutic outcome supports the high-efficiency of radiotherapy based on BMS@Pt2Au4 NPs in hypoxic tumors expressing PD-L1."

IO biomarker • Journal • Oncology • CALR • HMGB1 • PD-L1

Targeted Delivery of c(RGDfk)-Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy. (PubMed, Adv Sci (Weinh)) - "On the one hand, c(RGDfk)-functionalized liposomes containing carfilzomib (CRLPs) successfully transformed macrophages from M2 phenotype to M1 phenotype, enhancing immunotherapeutic responses. On the other hand, c(RGDfk)-functionalized liposomes encapsulating BMS-202 (BRLPs), a small molecule checkpoint inhibitor, interrupted the PD-1/PD-L1 axis and promoted the infiltration of cytotoxic T cells...These findings introduced an alternative approach to modulating the myeloma microenvironment and underscored the efficacy of hitchhiking neutrophils for bone marrow drug delivery. This strategy show advantages over traditional drug delivery methods in terms of improved efficacy and lowered toxicity."

Journal • Preclinical • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology