YHO-1701 / Yakult Honsha - LARVOL DELTA

Evaluating the specific STAT3 inhibitor YHO-1701 in ovarian cancer cell lines and patient-derived cell models: efficacy, mechanisms, and therapeutic potential. (PubMed, J Gynecol Oncol) - "Our results showed that YHO-1701 suppressed cell growth in PDCs of OC, accompanied by survivin inhibition, and a decrease in the number of peritoneal metastasis in the mice by YHO-1701, compared with those treated with control. Therefore, YHO-1701 could be a promising candidate agent for treating OC."

Journal • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • BIRC5

Combined therapeutic effect of YHO-1701 with PD-1 blockade is dependent on natural killer cell activity in syngeneic mouse models. (PubMed, Cancer Immunol Immunother) - "Furthermore, this combination therapy significantly inhibited tumor growth in an immunotherapy-resistant model of murine CMS5a fibrosarcoma. These results suggest that the combination of YHO-1701 with PD-1/PD-L1 blockade might be a new candidate for cancer immunotherapy involving the enhancement of NK cell activity in the tumor microenvironment."

Journal • Preclinical • Fibrosarcoma • Immune Modulation • Oncology • Sarcoma • Solid Tumor

STAT3 inhibition suppresses adaptive survival of ALK-rearranged lung cancer cells through transcriptional modulation of apoptosis. (PubMed, NPJ Precis Oncol) - "In xenograft study, the combination of YHO-1701 (STAT3 inhibitor) and alectinib significantly suppressed tumor regrowth after treatment cessation with near tumor remission compared with alectinib alone. Hence, this study provides new insights into combined therapeutic strategies for patients with ALK-rearranged lung cancer."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BCL2L1

Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines. (PubMed, Sci Rep) - "Of particular interest was the synergistic effect observed when YHO-1701 was combined with imatinib or dasatinib [breakpoint cluster region-abelson (BCR-ABL) inhibitors], osimertinib [epidermal growth factor receptor (EGFR) inhibitor], crizotinib, alectinib, or ceritinib [anaplastic lymphoma kinase (ALK) inhibitors]. The combination of YHO-1701 with alectinib resulted in significantly greater antitumor activity without exhibiting body weight loss in an NCI-H2228 [echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion] xenograft mouse model. Our results strongly suggest that the logical strategy in combination with the novel STAT3 inhibitor YHO-1701 and other mechanistically different targeted agents, could be a promising approach in future clinical settings."

Journal • Preclinical • Oncology • Solid Tumor • ALK • BCR • EML4

Antitumor activity of a novel oral STAT3 inhibitor YHO-1701. (PubMed, Cancer Sci) - "Thus, YHO-1701 has a favorable specificity for STAT3 and pharmacokinetics after oral treatment; it also contributed to the enhanced antitumor activity of sorafenib. The evidence presented here provides justification using this approach in future clinical settings."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor

Ex vivo cytotoxicity and in vivo anti-tumour activity of a novel highly selective STAT3 inhibitor YHO-1701 for ovarian and endometrial cancer (ESMO 2019) - "Our results demonstrated the efficacy of YHO-1701 for ovarian and endometrial cancer both ex vivo and in vivo through STAT3 signaling. Legal entity responsible for the study: The authors. Funding: Yakult Honsha."

Preclinical

A novel STAT3 inhibitor YHO-1701 inhibits ovarian and endometrial cancer cell growth, with augmented cytotoxicity in combination with an mTOR inhibitor (SGO 2019) - "Our results demonstrated efficacy of YHO-1701 for ovarian and endometrial cancer both in vitro and in vivo through STAT3 and mTOR pathways. Combination therapy of YHO-1701 and everolimus might show enhanced efficacy."

Combination therapy

A novel STAT3 inhibitor YHO-1701 inhibits ovarian and endometrial cancer cell growth, with augmented cytotoxicity in combination with an mTOR inhibitor (SGO 2019) - "Our results demonstrated efficacy of YHO-1701 for ovarian and endometrial cancer both in vitro and in vivo through STAT3 and mTOR pathways. Combination therapy of YHO-1701 and everolimus might show enhanced efficacy."

Combination therapy