salinomycin (HSB-1216) / Canton Strategic Holdings - LARVOL DELTA

Repurposing Polyether Ionophores to Target Stem-Like Compartments and Microenvironmental Resistance in Multiple Myeloma (IMS 2026) - "We hypothesized that the polyether ionophores salinomycin (SAL) and monensin (MON), known to kill cancer stem-like cells in solid tumors, would target the Hoechst-low side-population (SP) compartment of MM...Both compounds synergized (Chou-Talalay CI< 0.9) with bortezomib, carfilzomib, lenalidomide, pomalidomide, doxorubicin, dexamethasone and melphalan, and significantly reduced subcutaneous RPMI-S xenograft growth in NSG mice without overt toxicity. SAL and MON are mechanistically convergent, stroma-resistant and cancer stem-like cell-directed agents that dismantle the bioenergetic, translational and survival machinery of the MM SP compartment, synergize with standard MM therapies and show in vivo efficacy without overt toxicity, supporting their further development for MM combination strategies. This study was supported by the NextGenerationEU project No.09I03-03-V04-00451 (JJ)."

Hematological Malignancies • Multiple Myeloma • Solid Tumor • ANXA5 • BBC3 • CCNB1 • CDKN1A • CHAC1 • CHEK1 • DDIT3 • EIF4EBP1 • GDF15 • IRF4 • MAP1LC3B • MYC • PMAIP1 • SDC1 • SIRT1 • SQSTM1

NOVEL COMPOUND TRIGGERS MULTIPLE CELL DEATH PATHWAYS AND EXHIBITS ANTI-CANCER PROPERTIES AGAINST GASTROINTESTINAL CANCERS (UEGW 2026) - "Ten-point dose–response assays were compared with standard chemotherapeutics (5-fluorouracil for CRC, cisplatin for CCA) and salinomycin, a known anti-CSC agent.Cytotoxic mechanisms were investigated using inhibitors of apoptosis, necroptosis, and ferroptosis, followed by ATP and adenylate kinase luminescence assays. In conclusion, we identified a novel chemical scaffold that effectively targets both bulk tumor cells and CSCs by triggering multiple types of regulated cell death pathways. Additionally, the anti-cancer properties of the compound extend to different gastrointestinal tumors while showing a good safety profile, implying its potential for a broad range of application. Future work will dissect the precise mechanism of action.Supported by: FCT UID/04138/2025; 2023.01547.BD; STSM CA22125, COST; PTDC/MED-FAR/3492/2021, 2023.11531.PEX (https://doi.org/10.54499/2023.11531.PEX) FCT; LCF/PR/HR21/52410028, "la Caixa" Foundation."

Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CASP3 • CASP7 • GPX4 • SLC7A11

Salinomycin is effective for clinically relevant radioresistant oral squamous cell carcinoma cancer cells and their cancer stem cell marker positive fraction. (PubMed, Med Int (Lond)) - "On the whole, the present study indicates that Sal is effective in killing the radioresistant population in SAS cells, which comprise a large proportion of CSCs in oral cancer, that is, the CD24-/CD44+ fraction. Furthermore, clinically relevant radioresistant cells (SAS-R) are sensitive to Sal; therefore, further investigations are necessary."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • CD24

Targeting tumor heterogeneity using an injectable gelatin hydrogel for the dual elimination of cancer cells and cancer stem cells. (PubMed, Biomater Sci) - "To mitigate these challenges, we engineered an injectable in situ-forming gelatin hydrogel capable of the sustained, localized co-delivery of resveratrol (RES) and salinomycin (SAL), thereby simultaneously targeting both cancer cells and bCSCs...In vivo evaluation using a 4T1 murine breast cancer model confirmed that the localized, sustained delivery of RES and SAL from the injectable gelatin hydrogel produced a synergistic antitumor effect, markedly inhibiting tumor progression while substantially mitigating systemic toxicity relative to free-drug administration. Collectively, the sustained co-delivery from the in situ injectable gelatin hydrogel efficiently targets both the bulk tumor population and bCSCs, highlighting its potential as a therapeutic strategy to diminish bCSC-driven recurrence and improve overall breast cancer treatment efficacy."

Heterogeneity • Journal • Breast Cancer • Oncology • Solid Tumor

Enhanced mitochondrial fission promotes chemosensitivity via SHP-1 activity in triple-negative breast cancer. (PubMed, Mol Biol Rep) - "Our in vitro findings demonstrate that mitochondrial fission sensitizes TNBC cells to certain chemotherapeutics, and that SHP-1 critically regulates this response. This newly identified mechanism links mitochondrial dynamics to chemotherapeutic sensitivity, offering a potential pathway to overcome TNBC chemoresistance through targeted therapies."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • MFN2

First anticoccidial sensitivity test applied to Eimeria lata: evidence of reduced sensitivity to nicarbazin in a Brazilian field isolate. (PubMed, Vet Res Commun) - "When taken together and based on the interpretation criteria adopted in this study, these divergent results indicate reduced sensitivity to nicarbazin and sensitivity to lasalocid, salinomycin, and semduramicin, underlining the importance of multi-parameter approaches when conducting ASTs. Furthermore, although based on a single isolate, our results also raise the possibility that alternative rearing systems may harbor drug-resistant Eimeria strains, an epidemiological concern that warrants further investigation."

Journal

Tissue-specific molecular responses to salinomycin and their modulation by ionophore-antibiotic interactions in turkeys. (PubMed, Poult Sci) - "Furthermore, ionophore-antibiotic interactions significantly modulate SAL-induced molecular responses in a treatment-dependent manner. This study provides mechanistic insight into drug-drug interactions in poultry and highlights candidate biomarkers for monitoring toxicity in poultry."

Journal

Influence of Benzoic Acid and Oregano Essential Oil on Intestinal Histomorphology, Lesion Scores, and Tight Junction Gene Expression in Mixed Eimeria-Challenged Broiler Chickens. (PubMed, Avian Pathol) - "The study demonstrated that combined supplementation with benzoic acid (BA) and oregano essential oil (OEO) reduced Eimeria infectivity and improved faecal scores comparable to salinomycin, while enhancing intestinal integrity, and jejunal morphology. These effects, accompanied by increased expression of Zonula occludens-1 and Claudin-1, support the potential of BA and OEO as natural anticoccidial alternatives in broiler chickens."

Journal • Infectious Disease • CLDN1 • TJP1

A novel orally bioavailable benzoxazine-derived compound targets cancer stem cells and demonstrates in vivo efficacy in pancreatic cancer PDX models (ESMO-GI 2026) - "In vivo efficacy, pharmacokinetics, oral bioavailability, and tolerability were assessed in CSC-derived xenografts and a patient-derived pancreatic cancer (PDX) model.Results The compound demonstrated submicromolar IC50 values in pancreatic CSC-enriched models, exceeding the potency of salinomycin, with improved solubility and a favorable toxicity profile...In vivo, the compound showed oral bioavailability, favorable pharmacokinetics, and good tolerability, significantly delaying tumor initiation and suppressing tumor growth in both CSC-derived xenografts and pancreatic PDX models. Treated tumors exhibited reduced expression of Ki67, CD44 and vimentin.Conclusions This novel benzoxazine-derived compound demonstrates potent anti-CSC activity and robust preclinical efficacy in pancreatic cancer, supporting its translational potential to overcome resistance, improve treatment durability, and reduce relapse."

Cancer stem • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD44 • CEACAM1 • ENG • ERBB4 • HER-2 • KLF4 • L1CAM • MSLN • MUC1 • SOX2 • VIM

A senolytic ADC drives synthetic lethality and immune surveillance for senescent cancer cell destruction (EACR 2026) - "Introduction: Senolytics, drugs that selectively eliminate senescent cells, exhibit potent efficacy when combined with pro-senescence cancer therapies.Material and Using CRISPR/Cas9-based genetic screens across diverse senescent cancer cell models, we identified cFLIP (an extrinsic apoptosis inhibitor) and SLC25A23 (a mitochondrial calcium transporter) as common vulnerabilities exploitable for targeted elimination.Result and To recapitulate the biological effects of suppressing both genes, we engineered a senolytic antibody-drug conjugate (ADC) pairing the DR5-agonist antibody conatumumab with salinomycin, an antibiotic that disrupts mitochondrial homeostasis. Our study pioneers a "synergy-immune stimulating ADC" (siADC) framework that fuses apoptosis induction with pyroptotic immune activation, showing a potent senolytic efficacy in multiple animal models, combining with independent pro-senescence regimens that underscore a high translational viability."

ADC • Synthetic lethality • Oncology • CFLAR • IL18 • SLC25A23 • TNFRSF10B

Sub-inhibitory polyether ionophores enhance resistance plasmid transfer and transiently perturb the broiler gut resistome. (PubMed, J Antimicrob Chemother) - "Polyether ionophores can promote resistance dissemination phenotypes in vitro, but gut ecological resilience may limit long-term impacts after cessation of exposure under recommended dosing conditions. The transient resistome surge during the treatment suggests increased shedding and potential environmental dissemination via manure, warranting surveillance and risk assessment."

Journal • CNS Disorders • Psychiatry

Anticoccidial Resistance in Eimeria spp. From Thai Broiler Farms Using Shuttle Programs. (PubMed, Vet Med Int) - "A total of 112-day-old broiler chicks were used to evaluate sensitivity to three widely used anticoccidial agents: narasin combined with nicarbazin, salinomycin, and maduramicin...The findings highlight the emergence of moderate drug resistance even within these structured programs, emphasizing a critical practical relevance for the poultry industry. To sustain long-term efficacy in Thai broiler production, there is an urgent need for strategic drug rotation and the integration of alternative control measures, such as vaccination and bio-shuttle strategies."

Journal • Infectious Disease

Assessment of the application for modification of the terms of the authorisation of the feed additive consisting of Bacillus velezensisATCC PTA-6737 (PB6) for all pigs, all poultry species for fattening or reared for laying/breeding, laying hens, minor poultry species for laying and ornamental birds (Kemin Europa N.V.). (PubMed, EFSA J) - "The current authorisation for poultry for fattening or reared for laying/breeding, ornamental birds and pigs allows the simultaneous use of PB6 with the coccidiostats diclazuril, decoquinate, salinomycin sodium, narasin/nicarbazin, lasalocid A sodium, maduramycin ammonium, monensin sodium, narasin and robenidine hydrochloride in accordance with their respective conditions of authorisation as feed additives. With the present application, the applicant is seeking a modification of such authorisation to allow the simultaneous use of the additive with the authorised coccidiostats amprolium, nicarbazin, monensin/nicarbazin and semduramicin. Based on in vitro and in vivo studies, the FEEDAP Panel concluded that B. velezensis ATCC PTA-6737 is compatible with the coccidiostats amprolium, nicarbazin, monensin/nicarbazin and semduramicin when used in poultry species at the proposed conditions of use."

Journal

[Retracted] Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling. (PubMed, Exp Ther Med) - "[This retracts the article DOI: 10.3892/etm.2021.10378.]."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Ngt-1: a glycosyltransferase that confers resistance to three distinct antibiotic classes. (PubMed, J Biol Chem) - "Surprisingly, ngt-1 confers resistance to three structurally distinct antibiotic classes: novobiocin (aminocoumarin), fidaxomicin (tiacumicin), and salinomycin (polyether). To further explore Ngt-1's functional breadth, we performed steady-state kinetic and protein-structure studies, revealing Ngt-1 as a novel, broad-spectrum glycosyltransferase capable of inactivating antibiotics. These findings highlight the importance of exploring the environmental resistome to identify new resistance enzymes and to inform strategies to combat antimicrobial resistance."

Journal

Interaction of bi-nuclear gallium(III) complexes with human serum albumin and impact on potency towards osteosarcoma stem cells. (PubMed, Dalton Trans) - "Cytotoxicity studies demonstrate that HSA binding enhances the potency of complexes 4-7 towards both bulk osteosarcoma cells (U2OS) and OSC-enriched cells (U2OS-MTX). Moreover, the HSA-bound bi-nuclear gallium(III) complexes (HSA-4-7) more effectively inhibit three-dimensional sarcosphere formation and viability compared to clinically used metallodrugs cisplatin and carboplatin, and the established anti-cancer stem cell agent salinomycin."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Ionophore susceptibility of Eimeria zaria: First characterisation in a cryptic Eimeria species of chickens. (PubMed, Vet Parasitol) - "Here, the efficacy of three anticoccidial drugs, monensin + nicarbazin ("Monimax"), narasin ("Monteban"), and salinomycin ("Sacox"), has been evaluated against an E. zaria type specimen in vivo...These results indicate that E. zaria is broadly susceptible to ionophore anticoccidials but, as for other Eimeria species, reduced sensitivity can emerge under field conditions. The new qPCR assays provide sensitive, specific tools for improved monitoring and assessment of E. zaria infections, supporting improved understanding of occurrence and epidemiology."

Journal • Infectious Disease

Dendrimer cisplatin and salinomycin complexes as a new combination therapy for ovarian cancer (AACR 2025) - "Our results establish that HA-dendrimer-CIS and HA-dendrimer-SAL combination therapy may represent a novel therapeutic combination for treating OC."

Combination therapy • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • CD44 • RAD51

Salinomycin inhibits orthopoxvirus infection in vitro and in vivo by blocking endosomal acidification. (PubMed, Antiviral Res) - "Collectively, these preliminary in vitro and in vivo data identify salinomycin as a potential host-targeted anti-orthopoxvirus inhibitor, especially in combination with tecovirimat. Further comprehensive preclinical evaluations, including full toxicological profiling and validation in clinically relevant models, are needed to define its translational potential for MPXV and other orthopoxvirus infections."

Journal • Preclinical • Infectious Disease

Screening with a library of salinomycin derivatives identifies strong upregulators of CD20 antigen in malignant B cells (AACR 2025) - "We characterized a library of SAL derivatives in the context of their ability to induce CD20 antigen upregulation and found a dozen more efficient regulators. This discovery provides a rationale for the clinical evaluation of SAL derivatives to obtain better therapeutic responses in patients with B cell-derived malignancies."

IO biomarker • Late-breaking abstract • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • MYC

Improvement of the anti-tumor activity of NK cells and the efficacy of anti-CD20 monoclonal antibodies in the therapy of B cell-derived malignancies. (AACR 2024) - "We have found that members of a specific class of antibiotics, known as cation carriers, namely salinomycin (SAL), monensin (MON), narasin, and nigericin exhibit great CD20 antigen-upregulating abilities...Thus, the results of proteomics analysis explained why SAL- or MON-pretreated tumor cells were efficiently eliminated by NK cells, even in the absence of therapeutic mAb. In light of our discoveries, it seems reasonable to consider the cation carriers as promising drug candidates for the improvement of NK cell anti-tumor activity and potential treatment of B-cell non-Hodgkin lymphoma patients, in combination with anti-CD20 mAbs."

Clinical • IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD80 • CD86 • HLA-B • HLA-C • ICAM1 • PVR • ULBP2

Green propolis extract replaces salinomycin in the high-concentrate diet of sheep. (PubMed, Trop Anim Health Prod) - No abstract available

Journal

Eliminating cancer stem cells can inhibit progression of residual hepatocellular carcinoma after radiofrequency ablation. (PubMed, Int J Hyperthermia) - "In vivo, two tumor-bearing mice were used to evaluate residual tumor growth, and treatments included an extracellular signal-regulated kinase (ERK) inhibitor U0126 and salinomycin (Sal)...Incomplete RFA can accelerate cell proliferation, migration, and stemness in residual tumors. ERK inhibitor combined with Sal could inhibit cancer cell proliferation, migration, and stemness to synergically inhibit the progression of residual tumor."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Cyclometalated Rhodium(III) Polypyridyl Complexes with Anti-Cancer Stem Cell Activity. (PubMed, Organometallics) - "The 4,7-diphenyl-1,10-phenanthroline-bearing complex 4 exhibits activity against monolayer- and three-dimensionally cultured breast CSCs and osteosarcoma stem cells in the sub-micromolar to low micromolar range, outperforming the metallodrug cisplatin and the established anti-CSC agent salinomycin. Our results suggest that the reported rhodium-(III) scaffold, containing cyclometalated 2,2'-(phenylmethylene)-dipyridine, could be a useful synthon for the future development of anti-CSC rhodium complexes."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Salinomycin as a death switch: how gastric cancer cells choose their demise. (PubMed, Cell Death Discov) - "Notably, autophagy was a common RCD mechanism also in this preclinical model. Our findings suggest that Sal is a promising candidate for GC treatment, and understanding a tumor's specific molecular susceptibilities could enable the development of personalized therapeutic strategies."

Journal • Gastric Cancer • Oncology • Solid Tumor • BIRC5 • CASP3 • CD133 • GPX4 • SLC7A11