BMS-202 / BMS - LARVOL DELTA

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

Comprehensive Advanced Physicochemical Characterization and In Vitro Human Cell Culture Assessment of BMS-202: A Novel Inhibitor of Programmed Cell Death Ligand. (PubMed, Pharmaceutics) - "TEER studies indicated that BMS-202 does not disrupt the HaCaT cell barrier function. The findings from this study establish that BMS-202 has promising physicochemical and in vitro characteristics at therapeutic concentrations for topical applications, providing a foundation for future formulation development focused on skin-related cancers or localized immune modulation."

Journal • Metastases • Preclinical • Immune Modulation • Immunology • Oncology

Unlocking Benzosampangine's Potential: A Computational Approach to Investigating, Its Role as a PD-L1 Inhibitor in Tumor Immune Evasion via Molecular Docking, Dynamic Simulation, and ADMET Profiling. (PubMed, Bioinform Biol Insights) - "Molecular docking predicted that benzosampangine exhibits a strong binding affinity for PD-L1 (-9.4 kcal/mol) compared with established controls such as CA-170 (-6.5 kcal/mol), BMS-202 (-8.6 kcal/mol), and pyrvinium (-8.9 kcal/mol)...MMGBSA analysis calculated a binding free energy (ΔGbind) of -39.39 kcal/mol for the benzosampangine-PD-L1 complex, with significant contributions from Coulombic, lipophilic, and Van der Waals interactions, validating the predicted docking results. This study investigates in silico benzosampangine, predicting its better molecular interactions and pharmacokinetic profile compared with several already known PD-L1 inhibitors."

Journal • Oncology

Liposomal chlorin e6-mediated photodynamic therapy induces cell pyroptosis and promotes anti-tumor immune effects in breast cancer. (PubMed, J Photochem Photobiol B) - "The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor...staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches."

Journal • Breast Cancer • Oncology • Solid Tumor

Radiation-activated PD-L1 aptamer-functionalized nanoradiosensitizer to potentiate antitumor immunity in combined radioimmunotherapy and photothermal therapy. (PubMed, J Mater Chem B) - "Additionally, the ICB inhibitor BMS-202 synergizes with the PD-L1 aptamer-assisted nanoradiosensitizer to block the PD-L1 receptor, promoting T cell activation. Furthermore, this nanoradiosensitizer exhibits exceptional photothermal conversion efficiency, amplifying the ICD effect. The PD-L1-targeted nanoradiosensitizer effectively inhibits primary tumor growth and eliminates distant tumors, underscoring the potential of this strategy in optimizing both radioimmunotherapy and photothermal therapy."

Journal • Oncology • PD-L1

EXPLORING BLOOD-BRAIN BARRIER-PENETRATING DRUGS FOR THE IDENTIFICATION OF NOVEL THERAPIES IN GLIOBLASTOMA (SIOP 2024) - " Seven drugs: Obatoclax (Mesylate), COG1410, Fingolimod, Ozanimod, Lonafarnib, BMS-202 and Bazedoxifene (acetate) were screened out as potential candidates, with consistent efficacy against glioblastoma cells, providing promising avenues for standalone therapies in GBM or as enhancers of existing conventional chemotherapy regimens. This multi-faceted approach aims to develop personalized and effective treatment strategies for the challenging landscape of glioblastoma tumors. This work was supported by FAPESP grant numbers 2022/09037-3, National Council for Scientific and Technological Development (CNPq, MCTI, Brazil) grant number 406484/2022-8 (INCT BioOncoPed)"

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

BMS202, a small molecule inhibitor of PD-L1, inhibiting metastasis in PDAC (KSMO 2024) - No abstract available

Oncology

Preparation and effects of functionalized liposomes targeting breast cancer tumors using chemotherapy, phototherapy, and immunotherapy. (PubMed, J Nanobiotechnology) - "BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells...We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS...This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

iRGD-mediated liposomal nanoplatforms for improving hepatocellular carcinoma targeted combination immunotherapy and monitoring tumor response via IVIM-MRI. (PubMed, J Mater Chem B) - "Herein, we synthesized iRGD-modified pH-sensitive liposomal nanoparticles co-encapsulating lenvatinib (Len) and the small molecule PD-1/PD-L1 inhibitor BMS-202 (iRGD-lip@Len/BMS-202) to address issues related to inadequate tumor enrichment and distinct pharmacokinetics of these drugs. Collectively, the combination of Food and Drug Administration (FDA)-approved drugs with iRGD-modified liposomes presents a promising strategy for HCC treatment. Simultaneously, IVIM-MRI provides a non-invasive method to accurately predict the response to this nanodrug."

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