IBR120 / University of California - LARVOL DELTA

Inhibitors of RAD51 as potential novel therapies in Acute Myeloid Leukemia (ASH 2025) - "Furthermore, these compounds often exhibit strong synergy and at least additivity in combination with both on-label and off-label use of FDA-approved compounds, as well as investigational molecularly-targeted agents, in relevant cell lines; these include FLT3 inhibitors quizartinib, gilteritinib and tuspetinib ((in MV-4-11 and HL60 cell lines) and BCR/ABL inhibitors (imatinib and regorafenib) in the K562 cell line (AACR 2025)...We have confirmed the IBRs inhibit multiple RAD51 functions including hydroxyurea-induced RAD51 focus formation, HRR by DR-GFP assay, and RS protection by RPA focus formation and a DNA fibre assay...JKYN-1 is a partially optimized (more soluble and more potent) version of IBR120 but is not resistant to degradation by liver microsomes or sufficiently capable of entry into target cells...Treatment dose and combinations will be pre-screened using a highly predictive cell line as a surrogate of human cancer stem cells for subsequently AML patient..."

Acute Myelogenous Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Solid Tumor • BRCA1 • BRCA2 • FLT3 • HRD • RAD51

Antiproliferative activity of EC359, an inhibitor of leukemia inhibitory factor receptor (LIF-R), singly and in combination with chemotherapy drugs against pancreatic cancer cell lines (AACR 2022) - "Although combination chemotherapy treatments such as FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan), gem-abraxane (gemcitabine and nab-paclitaxel) and GTX (gemcitabine, docetaxel and capecitabine) have improved survival of pancreatic cancer patients incrementally, 5-year-survival for this disease remains dismal...EC359 was also synergistic with IBR120 (a novel small molecule inhibitor of RAD51) against PANC-1 cells...The nanomolar activity of EC359 against pancreatic cancer cell lines makes it a good candidate for potential treatment of this generally refractory disease. The synergistic interaction of EC359 with standard-of-care drugs provides an opportunity for increasing the therapeutic index for these agents, and ultimately improving clinical outcomes for pancreatic cancer and other cancers against which EC359 is currently in clinical trial."

Combination therapy • Preclinical • Breast Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Solid Tumor • LIFR • RAD51

Synergistic antiproliferative activity of novel RAD51 inhibitor JKYN-1 and its mesylate salt with standard-of-care cancer drugs (AACR 2022) - "To improve the activity and potentially increase selectivity for inhibiting RAD51, modifications were made to the structure of IBR120 using a virtual drug-protein docking program, yielding the compound JKYN-1...The chemotherapy agents included inhibitors of epidermal growth factor receptor (osimertinib, afatinib), other tyrosine kinases (regorafenib, imatinib), sex steroid receptors (4-OH-tamoxifen, enzalutamide), and microtubule function (docetaxel)...Individual combinations will be presented. The ability of JKYN-1 to enhance antiproliferative activity of a wide variety of anticancer agents, and its potential selectivity for cancer cells, make possible the future use of RAD51 inhibitors as systemic therapy potentiators to improve clinical outcomes."

Oncology • EGFR • RAD51

Synergistic antiproliferative activity between anticancer drugs and RAD51 inhibitors IBR2 and IBR120 (AACR 2019) - "...The chemotherapy agents included inhibitors of epidermal growth factor receptor (EGFR) family (osimertinib, afatinib, lapatinib), Bcr-Abl (imatinib), B-raf (vemurafenib), multiple tyrosine kinases (regorafenib), sex steroid receptors (4-OH-tamoxifen, enzalutamide), and microtubules (vincristine)...In the NSCLC cell lines, IBR2, IBR120, osimertinib, gefitinib, and afatinib decreased the cellular content of RAD51 by over 80% within 24 h (western blot with antibody 3C10), at concentrations at or lower than their IC50 value...Studies are ongoing to determine the effect of IBR120 on growth of explants of the NSCLC cell line H1650 in mice, after which the combination of IBR120 and osimertinib will be tested in vivo. The ability of IBR2 and IBR120 to enhance antiproliferative activity of a wide variety of anticancer agents and their potential selectivity for cancer cells make possible their future use as systemic therapy potentiators to improve clinical outcomes."