AIT-102 / EntreChem, OrphAI Therap - LARVOL DELTA

Mechanism Studies of HDACi combined with SP/KLF inhibitors in the treatment of H3K27M-mutant diffuse intrinsic pontine gliomas (AACR 2025) - "Encouragingly, targeted intervention with EC-8042 effectively reverses this activated regulatory network by HDACi, thereby mitigating tumor adaptation and invasiveness...Transcriptomic analysis further supports that the combination treatment drives transcriptional programs correlating with favorable prognosis in DIPG patients. Therefore, employing DIPG models, this study provides critical mechanistic understanding of the limited responsiveness to HDACi in solid tumors, thereby laying the groundwork for the innovation of novel combination strategies."

Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Targeting the SP/KLF Transcriptional Regulatory Network Synergizes with HDAC Inhibition to Impede Progression of H3K27M Diffuse Intrinsic Pontine Glioma. (PubMed, Cancer Res) - "SP1 depletion or inhibition of SP/KLF DNA binding with EC-8042, an optimized mithramycin analog, significantly suppressed the proliferation and invasiveness of H3K27M-DIPG cells...Transcriptomic profiling indicated that this combinatorial strategy induced transcriptional changes associated with improved prognosis in DIPG patients. Thus, this study identifies a therapeutic approach for H3K27M-mutated DIPGs and sheds light on the limitations of HDACi in treating solid tumors."

Journal • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

Mithramycin and its analogs: Molecular features and antitumor action. (PubMed, Pharmacol Ther) - "They down-regulate gene expression in various cellular processes, including Sp1-responsive genes that control tumor development. Moreover, MTA and several mithralogs, such as EC-8042 (DIG-MSK) and EC-8105, effectively treat Ewing sarcoma by inhibiting transcription controlled by the oncogenic EWS-FLI1 transcription factor."

Journal • Review • Ewing Sarcoma • Oncology • Ovarian Cancer • Prostate Cancer • Sarcoma • Solid Tumor • EWSR1 • FLI1

Abrogation of stemness in osteosarcoma by the mithramycin analog EC-8042 is mediated by its ability to inhibit NOTCH-1 signaling. (PubMed, Biomed Pharmacother) - "Overall, these data highlight the relevant role that NOTCH1 signaling plays in mediating stemness in osteosarcoma. Moreover, we demonstrate that EC-8042 is powerful inhibitor of NOTCH signaling and that the anti-CSC activity of this mithramycin analog highly rely on its ability to repress this pathway."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • HES1 • NOTCH1

AI Therapeutics Announces the Acquisition of Novel Cancer Drug Candidate EC-8042 (AIT-102) (GlobeNewswire) - "AI Therapeutics, Inc...today announced the acquisition of EntreChem, S.L.’s investigational drug candidate EC-8042 (redesignated AIT-102), a novel targeted cancer therapy in development for rare pediatric and other cancers...AIT-102 specifically targets the mutations responsible for the formation and progression of two notable pediatric tumors, rhabdoid tumors and Ewing sarcoma, and holds the potential to treat a broader family of tumors that share a common mechanism of mutated or dysregulated SWI/SNF activity."

Licensing / partnership • Ewing Sarcoma • Oncology • Rhabdoid Tumor • Sarcoma

SETDB1 in cancer: overexpression and its therapeutic implications. (PubMed, Am J Cancer Res) - "Accordingly, we review several methods that have been used to target SETDB1, such as using Mithramycin A, Mithralog EC-8042, 3'-deazaneplanocin A (DZNep), and paclitaxel. Finally, we conclude by highlighting remaining gaps in knowledge and challenges surrounding SETDB1. Ultimately, our review captures the wide scope of findings on SETDB1's history, function, its implications in cancer, and provides suggestions for future research in the field."

Journal • Review • Acute Myelogenous Leukemia • Brain Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioma • Hematological Malignancies • Hepatology • Inflammatory Arthritis • Leukemia • Liver Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Solid Tumor • AR • SETDB1

[VIRTUAL] Generation and Characterization of Bone Sarcoma Doxorubicin-Resistant Primary Cell Lines (EACR 2021) - "Their treatment still rely on the use of chemotherapeutic drugs (doxorubicin (DOX), ifosfamide, methotrexate and/or cisplatin) combined with an adequate surgical resection...Although all DOX-resistant models also acquired resistance to mithramycin analogues and other drugs, they became slightly more sensitive to cisplatin or methotrexate than parental cells. Finally, resistant models also showed a worse response to DOX in vivo and new cell lines derived from resistant xenografts kept the resistance levels observed before the in vivo growth. Conclusion Here we used primary cell lines to generate pioneer drug-resistant models suitable for characterizing altered mechanisms in DOX-resistant bone sarcomas."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

[VIRTUAL] Dasatinib promotes cancer stem cell properties in head and neck carcinoma cells that are effectively suppressed by the mithramycin analog EC-8042 (EACR 2021) - "Furthermore, combination treatment of dasatinib with EC-8042 provided favourable complementary anti-proliferative, anti-invasive and anti-CSC functions without any noticeable adverse interactions between both agents Conclusion This study unveils striking deleterious stem cell-promoting activities of the SFK inhibitors dasatinib and saracatinib that could underlie the lack of clinical efficacy observed in HNSCC patients. Our findings support novel combinational strategies with EC-8042 for clinical testing in HNSCC patients."

Cancer stem cells • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] Generation and Characterization of Bone Sarcoma Doxorubicin-Resistant Primary Cell Lines (EACR 2021) - "Their treatment still rely on the use of chemotherapeutic drugs (doxorubicin (DOX), ifosfamide, methotrexate and/or cisplatin) combined with an adequate surgical resection...Although all DOX-resistant models also acquired resistance to mithramycin analogues and other drugs, they became slightly more sensitive to cisplatin or methotrexate than parental cells. Finally, resistant models also showed a worse response to DOX in vivo and new cell lines derived from resistant xenografts kept the resistance levels observed before the in vivo growth. Conclusion Here we used primary cell lines to generate pioneer drug-resistant models suitable for characterizing altered mechanisms in DOX-resistant bone sarcomas."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

[VIRTUAL] Generation and Characterization of Bone Sarcoma Doxorubicin-Resistant Primary Cell Lines (EACR 2021) - "Their treatment still rely on the use of chemotherapeutic drugs (doxorubicin (DOX), ifosfamide, methotrexate and/or cisplatin) combined with an adequate surgical resection...Although all DOX-resistant models also acquired resistance to mithramycin analogues and other drugs, they became slightly more sensitive to cisplatin or methotrexate than parental cells. Finally, resistant models also showed a worse response to DOX in vivo and new cell lines derived from resistant xenografts kept the resistance levels observed before the in vivo growth. Conclusion Here we used primary cell lines to generate pioneer drug-resistant models suitable for characterizing altered mechanisms in DOX-resistant bone sarcomas."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

[VIRTUAL] Dasatinib promotes cancer stem cell properties in head and neck carcinoma cells that are effectively suppressed by the mithramycin analog EC-8042 (EACR 2021) - "Furthermore, combination treatment of dasatinib with EC-8042 provided favourable complementary anti-proliferative, anti-invasive and anti-CSC functions without any noticeable adverse interactions between both agents Conclusion This study unveils striking deleterious stem cell-promoting activities of the SFK inhibitors dasatinib and saracatinib that could underlie the lack of clinical efficacy observed in HNSCC patients. Our findings support novel combinational strategies with EC-8042 for clinical testing in HNSCC patients."

Cancer stem cells • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] Dasatinib promotes cancer stem cell properties in head and neck carcinoma cells that are effectively suppressed by the mithramycin analog EC-8042 (EACR 2021) - "Furthermore, combination treatment of dasatinib with EC-8042 provided favourable complementary anti-proliferative, anti-invasive and anti-CSC functions without any noticeable adverse interactions between both agents Conclusion This study unveils striking deleterious stem cell-promoting activities of the SFK inhibitors dasatinib and saracatinib that could underlie the lack of clinical efficacy observed in HNSCC patients. Our findings support novel combinational strategies with EC-8042 for clinical testing in HNSCC patients."

Cancer stem cells • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] Generation and Characterization of Bone Sarcoma Doxorubicin-Resistant Primary Cell Lines (EACR 2021) - "Their treatment still rely on the use of chemotherapeutic drugs (doxorubicin (DOX), ifosfamide, methotrexate and/or cisplatin) combined with an adequate surgical resection...Although all DOX-resistant models also acquired resistance to mithramycin analogues and other drugs, they became slightly more sensitive to cisplatin or methotrexate than parental cells. Finally, resistant models also showed a worse response to DOX in vivo and new cell lines derived from resistant xenografts kept the resistance levels observed before the in vivo growth. Conclusion Here we used primary cell lines to generate pioneer drug-resistant models suitable for characterizing altered mechanisms in DOX-resistant bone sarcomas."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

[VIRTUAL] Dasatinib promotes cancer stem cell properties in head and neck carcinoma cells that are effectively suppressed by the mithramycin analog EC-8042 (EACR 2021) - "Furthermore, combination treatment of dasatinib with EC-8042 provided favourable complementary anti-proliferative, anti-invasive and anti-CSC functions without any noticeable adverse interactions between both agents Conclusion This study unveils striking deleterious stem cell-promoting activities of the SFK inhibitors dasatinib and saracatinib that could underlie the lack of clinical efficacy observed in HNSCC patients. Our findings support novel combinational strategies with EC-8042 for clinical testing in HNSCC patients."

Cancer stem cells • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Mithramycin induces promoter reprogramming and differentiation of rhabdoid tumor. (PubMed, EMBO Mol Med) - "These effects occurred at concentrations not associated with DNA damage and were not due to global chromatin remodeling or widespread gene expression changes. Importantly, a single 3-day infusion of EC8042 caused dramatic regressions of RT xenografts, recapitulated the increase in H3K27me3, and cellular differentiation described in vitro to completely cure three out of eight mice."

Journal • Oncology • Pediatrics • Rhabdoid Tumor • Sarcoma • SMARCB1