BMS-202 / BMS - LARVOL DELTA

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

Computational Approach for the Development of pH-Selective PD-1/PD-L1 Signaling Pathway Inhibition in Fight with Cancer. (PubMed, Cancers (Basel)) - "The compound MolPort-001-742-690 emerged as a promising pH-selective inhibitor, showing a significant affinity for PD-L1 in acidic conditions and lower toxicity compared to known inhibitors like BMS-202 and LP23. A detailed 1000 ns molecular dynamics simulation confirmed the stability of the inhibitor-PD-L1 complex under acidic conditions. This research highlights the potential of using in silico techniques to discover novel pH-selective inhibitors, which, after experimental validation, may enhance the precision and reduce the toxicity of immunotherapies, offering a transformative approach to cancer treatment."

Journal • Oncology • PD-L1

Design, synthesis, pharmacological evaluation, and computational study of benzo[d] isothiazol-based small molecule inhibitors targeting PD-1/PD-l1 interaction. (PubMed, Eur J Med Chem) - "In this work, based on BMS-202 and our previous work YLW-106, a series of compounds with benzo[d]isothiazol structure as scaffold were designed and synthesized...Multi-computational methods, including molecular docking, molecular dynamics, MM/GBSA, MM/PBSA, Metadynamics, and QM/MM MD were utilized on PD-L1 dimer complexes, which revealed the binding modes and dissociation process of LLW-018 and C2-symmetric small molecule inhibitor LCH1307. These results suggested that LLW-018 exhibited promising potency as a PD-1/PD-L1 inhibitor for further investigation."

Journal • Oncology

Construction of Hierarchically Biomimetic Iron Oxide Nanosystems for Macrophage Repolarization-Promoted Immune Checkpoint Blockade of Cancer Immunotherapy. (PubMed, ACS Appl Mater Interfaces) - "BMS-202, a small-molecule PD-1/PD-L1 inhibitor that has a lower price, higher stability, lower immunogenicity, and higher tumor penetration ability compared with antibodies, was loaded together with pH-sensitive NaHCO3 inside hollow Fe3O4 NPs, followed by wrapping with macrophage membranes...A series of in vitro and in vivo assessments revealed that FBN@M could reprogram M2 TAMs into M1 TAMs and block the PD-1/PD-L1 pathway, which eventually induced T cell activation and the secretion of TNF-α and IFN-γ to kill the tumor cells. FBN@M has shown a significant immunotherapeutic efficacy for tumor treatment."

Checkpoint block • Checkpoint inhibition • Journal • Oncology • IFNG • TNFA

The natural marine product fucoidan sensitizes breast tumours to anti-PD-1 immunotherapy in vivo (EACR 2024) - "We investigated seaweed fucoidan, a marine drug with promising anti-cancer and immunomodulatory effects, as an adjuvant to an anti-PD-1/PDL-1 inhibitor (BMS-202)...Next, we assessed the tumour tissue levels of cleaved caspase-3 and Ki-67 (marker of proliferation Kiel 67) using immunohistochemistry as well as phosphorylated extracellular regulated kinase (p-ERK1/2), phosphorylated protein kinase-B (p-Akt) and phosphorylated P38 mitogen-activated protein kinase (p-P38-MAPK) using Western blotting. Results revealed a significantly higher level of the pro-apoptotic caspase 3 along with significantly (p<0.05) lower levels of the proliferative (Ki67) and tumorigenic signals (p-ERK1/2, p-Akt and p-P38-MAPK) by 69%, 85% and 87.5%, respectively, in the tumour tissues of the combination treated group versus control.Conclusion Natural marine fucoidan augmented the anti-tumour activity of anti-PD-1 warranting further research into the underlying mechanisms."

IO biomarker • Preclinical • Breast Cancer • Oncology • Solid Tumor • CASP3

Discovery of Novel Proteolysis-Targeting Chimera Molecules as Degraders of Programmed Cell Death-Ligand 1 for Breast Cancer Therapy. (PubMed, J Med Chem) - "Here, a novel PD-L1 proteolysis-targeting chimera (PROTAC) library was designed and synthesized utilizing the PD-L1 inhibitor BMS202 and the E3 ligand PG as foundational components...Thus, these results suggest that PA8 could be a novel strategy for cancer immunotherapy in the 4T1 tumor model. Although PA8 exhibits weaker degradation activity in some human cancer cells, it still provides a certain basis for further research on PD-L1 PROTAC."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • PD-L1

Checkpoint Inhibitor Pathway Dysfunction in Pulmonary Fibrosis (ATS 2024) - " We generated young (3-month) and aged (18-month) cohorts of our published IER-SP-CI73T mouse model of spontaneous pulmonary fibrosis (PF) and induced mutant Sftpc expression with 2 sequential daily doses of tamoxifen (Tam) delivered by oral gavage...The effect of a small molecule PD-1/PDL-1 pathway inhibitor (BMS-202) was assessed in an intervention protocol (5 mg/kg) administered daily beginning on day 12... Collectively data from these studies show that aged Sftpc mice exhibit a more severe fibrotic phenotype accompanied by alterations in re-programmed AT2 cell numbers and enhanced PD-L1 expression. We propose a model wherein pro-fibrotic epithelial populations escape immune surveillance avoiding clearance by CD3+CD8+PD1+ T cells to promote a fibrogenic niche."

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

Anti-lung cancer synergy of low-dose doxorubicin and PD-L1 blocker co-delivered via mild photothermia-responsive black phosphorus. (PubMed, Drug Deliv Transl Res) - "To prove this idea, DOX and BMS-202 (a PD-L1 blocker) were loaded to black phosphorus (BP) nanoparticles after dosage titration to yield the BMS-202/DOX@BP composites that rapidly disintegrated and released drug cargo upon mild photothermal heating at 40 °C. The synergetic actions involved highlight the value of TAM and the significance of modulating tumor cell-TAM cross-talk in tumor therapy. Photothermia-responsive BP provides an efficient platform to translate this strategy into targeted, efficacious tumor therapy."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HMGB1

Metabolic remodeling by the PD-L1 inhibitor BMS-202 significantly inhibits cell malignancy in human glioblastoma. (PubMed, Cell Death Dis) - "Mechanistically, it reduces the expression of PD-L1 on the surface of GBM cells and interrupts the PD-L1-AKT-BCAT1 axis independent of mTOR signaling. Taken together, we conclude that BMS-202 is a promising therapeutic candidate for patients with GBM by remodeling their cell metabolism regimen, thus leading to better survival."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BCAT1 • PD-L1

Targeting HER2-positive breast cancer cells by a combination of dasatinib and BMS-202: Insight into the molecular pathways. (PubMed, Cancer Cell Int) - "Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer."

IO biomarker • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDH1 • HER-2 • MAPK8 • VIM