briciclib (ON 013105) / Traws Pharma - LARVOL DELTA

Synthesis and modification of Briciclib phosphonate analogs for the topical treatment of psoriasis (ISDS 2025) - "Our results identify eIF4E as a promising molecular target for psoriasis and support the development of safe, topically applicable eIF4E inhibitors as an innovative treatment approach for patients with mild to moderate disease."

Dermatology • Immunology • Inflammation • Psoriasis • EIF4A1 • EIF4A2 • EIF4E • EIF4G1 • TNFA

An in vitro pharmacogenomic approach reveals subtype-specific therapeutic vulnerabilities in atypical teratoid/rhabdoid tumors (AT/RT). (PubMed, Pharmacol Res) - "Subtype-dependent drug response profiles demonstrated sensitivity of AT/RT-SHH cell lines to B-cell lymphoma 2 (BCL2) and heat shock protein 90 (HSP90) inhibitors, and increased activity of microtubule inhibitors, kinesin spindle protein (KSP) inhibitors, and the eukaryotic translation initiation factor 4E (eIF4E) inhibitor briciclib in a subset of AT/RT-MYC cell lines. In summary, our in vitro pharmacogenomic approach revealed preclinical evidence of tumor type- and subtype-specific therapeutic vulnerabilities in AT/RT cell lines that may inform future in vivo and clinical evaluations of novel pharmacological strategies."

IO biomarker • Journal • Preclinical • B Cell Lymphoma • Brain Cancer • CNS Tumor • Embryonal Tumor • Glioma • Lymphoma • Malignant Glioma • Medulloblastoma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • BCL2 • CDC37 • EIF4E • HSP90AA1 • SMARCA4 • SMARCB1

Novel targets for BRAFV600E and BRAFV600ERAC1P29S drug resistant melanoma (AACR 2024) - "Rac1 P29S -transfected and PLX4720 resistant cell lines had an increase in the Mek/Erk signaling pathway...Drugs that target different subunits of the eIF4F complex (CR-1-31-B, Ribavirin and Briciclib) also decrease BRAFV600E/RAC1P29S and the DR melanoma cell lines growth specifically...When tested in a syngraft model, CR-1-31-B and rapamycin reduced tumor size when using YUMM1.7, YUMM1.7- RAC1P29S and YUMM1.7 RAC1P29S-DR cell lines. Next, we sought to investigate the effect of inhibiting mTOR and eiF4F in the PD-1/PD-L1 axis in tumor cells and tumor associated dendritic cells and macrophages, and how targeting these modifies the tumor microenvironment."

IO biomarker • Melanoma • Oncology • Solid Tumor • BRD4 • CDK9 • EIF4A1 • EIF4E • EIF4G1 • MYC • RAC1 • SMAD3

Bricilib - a new strategy for the treatment of psoriasis targeting eukaryotic translation initiation factor 4E (ISDS 2023) - "Methodology: We used specific eIF4E siRNA and/or briciclib, an eIF4E inhibitor, in HaCaT cells, a 3D human psoriasis tissue model, and in two psoriasis mouse models (imiquimod and TGFß) to investigate protein and mRNA expression of eIF4E itself and its two complex partners, eIF4A and eIF4G, as well as of other eIFs (eg, eIF1A, eIF2α, eIF3A, eIF3B, eIF5, and eIF6). This work opens up possibilities for the development of novel topical strategies for the treatment of psoriasis targeting eIF4E and/or other eIFs."

Dermatology • Immunology • Inflammation • Psoriasis • EIF1AX • EIF4A1 • EIF4A2 • EIF4E • EIF4G1 • EIF6 • KRT16 • TNFA

Eukaryotic translation initiation factor 4E (eIF4E) as a target of anti-psoriatic treatment. (PubMed, J Invest Dermatol) - "The inhibition of eIF4E by siRNA or briciclib, an eIF4E small molecule inhibitor, downregulated the expression of eIF4E itself and its two complex partners eIF4A and G, as well as other eIFs (e.g. eIF1A, eIF2α, eIF3A, eIF3B, eIF5 and eIF6). This inhibition also abolished psoriatic inflammation in both the imiquimod and TGFß mouse model, as well as in a human 3D-psoriasis tissue model...These results demonstrate translational imbalance and underline the crucial role played by eIF4E and other eIFs in the pathophysiology of psoriasis. This work opens up avenues for the development of novel topical anti-psoriatic treatment strategies by targeting eIF4E."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • EIF1AX • EIF4A1 • EIF4E • EIF6 • IL17A • IL1B • IL22 • KRT16 • TNFA

Eukaryotic translation initiation factor 4E (eIF4E) as a target of anti-psoriatic treatment (ESDR 2022) - "We used specific eIF4E siRNA or briciclib an eIF4E inhibitor in HaCaT cells, a human 3D-psoriasis tissue model as well as the imiquimod and TGFß mouse model to downregulate the protein and mRNA expression of eIF4E itself and its two complex partners eIF4A and G, as well as other eIFs (e.g. eIF1A, eIF2α, eIF3A, eIF3B, eIF5 and eIF6). These results demonstrate translational imbalance and underline the crucial role played by eIF4E and other eIFs in the pathophysiology of psoriasis. This work opens up new avenues for the development of novel topical anti-psoriatic treatment strategies by targeting eIF4E and/or other eIFs."

Dermatology • Immunology • Inflammation • Psoriasis • EIF1AX • EIF4A1 • EIF4E • EIF6 • IL17A • IL1B • IL22 • TNFA

Inhibiting Eukaryotic Initiation Factor 4E (eIF4E) in Non-Small Cell Lung Cancer (EACR 2022) - "Material and Methods H460 (large cell carcinoma), H520 (squamous cell carcinoma), and A549 (adenocarcinoma) cells were treated with 0.1 to 0.5 µM (in 0.1 µM increments) of Briciclib® and 4E1RCat® separately...These will later be independently studied in combination with gene knockdown approaches on NSCLC and healthy cell controls, with the aim of obtaining a synergistic effect which exhibits enhanced anti-proliferative action with potentially lower toxicity to healthy cells. Data will be further evaluated through protein studies on suitable drug target endpoints."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • EIF4E

Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=26; Terminated; Sponsor: Onconova Therapeutics, Inc.; N=54 ➔ 26; Suspended ➔ Terminated; The study was placed on hold by the FDA due to manufacturing issues and was not restarted.

Clinical • Enrollment change • Trial termination • Oncology • Solid Tumor