seocalcitol (CB1089) / LEO Pharma, J&J - LARVOL DELTA

Proteasome inhibitors reduce thrombospondin-1 release in human dysferlin-deficient myotubes. (PubMed, BMC Musculoskelet Disord) - "Our findings indicate that the ubiquitin-proteasome system might not be the main mechanism of mutant dysferlin degradation. However, its inhibition could help to improve muscle inflammation by reducing TSP-1 release."

Journal • Immunology • Inflammation • Muscular Dystrophy • Targeted Protein Degradation • Myogenin • THBS1

Gene expression pattern in response to cholecalciferol supplementation highlights cubilin as a major protein of 25(OH)D uptake in adipocytes and male mice white adipose tissue. (PubMed, Endocrinology) - "...Vitamin D receptor (VDR) agonist (EB1089) and RNA interference approaches demonstrated that VDR was involved in this regulation...Furthermore, chemical inhibitor and by RNA inference analysis demonstrated that cubilin was involved in 25(OH)D uptake by adipocytes.This study established an overall snapshot of the genes regulated by cholecalciferol in mouse WAT and cell-autonomously in adipocytes. We highlighted that the regulation of cubilin expression is mediated by a VDR-dependent mechanism, and we demonstrated that cubilin is involved in 25(OH)D uptake by adipocytes."

Journal • Biosimilar

Chemopreventive effect of progestin and vitamin D in the mogp-TAG ovarian cancer mouse model (SGO 2020) - "DMPA and DMPA/EB1089 combination treatments significantly reduced the tumor burden and aberrant p53 expression in the fallopian tube of mice compared to vehicle-treated animals. EB1089-treated animals showed a significant reduction in the accumulation of p53 but to a lesser extent than that observed in DMPA and EB1089/DMPA groups. These data provide evidence supporting the hypothesis that progestin alone or in combination with vitamin D may be used for prevention of ovarian cancer."

Preclinical

Chemopreventive effect of progestin and vitamin D in the mogp-TAG ovarian cancer mouse model (SGO 2020) - "DMPA and DMPA/EB1089 combination treatments significantly reduced the tumor burden and aberrant p53 expression in the fallopian tube of mice compared to vehicle-treated animals. EB1089-treated animals showed a significant reduction in the accumulation of p53 but to a lesser extent than that observed in DMPA and EB1089/DMPA groups. These data provide evidence supporting the hypothesis that progestin alone or in combination with vitamin D may be used for prevention of ovarian cancer."

Preclinical

Chemopreventive effect of progestin and vitamin D in the mogp-TAG ovarian cancer mouse model (SGO 2020) - "DMPA and DMPA/EB1089 combination treatments significantly reduced the tumor burden and aberrant p53 expression in the fallopian tube of mice compared to vehicle-treated animals. EB1089-treated animals showed a significant reduction in the accumulation of p53 but to a lesser extent than that observed in DMPA and EB1089/DMPA groups. These data provide evidence supporting the hypothesis that progestin alone or in combination with vitamin D may be used for prevention of ovarian cancer."

Preclinical

Chemopreventive effect of progestin and vitamin D in the mogp-TAG ovarian cancer mouse model (SGO 2020) - "DMPA and DMPA/EB1089 combination treatments significantly reduced the tumor burden and aberrant p53 expression in the fallopian tube of mice compared to vehicle-treated animals. EB1089-treated animals showed a significant reduction in the accumulation of p53 but to a lesser extent than that observed in DMPA and EB1089/DMPA groups. These data provide evidence supporting the hypothesis that progestin alone or in combination with vitamin D may be used for prevention of ovarian cancer."

Preclinical

Therapeutic efficacy of Vitamin D in experimental c-MET-beta-catenin-driven hepatocellular cancer. (PubMed, Gene Expr) - "In conclusion, although 1α,25(OH)₂D₃ is reported to inhibit β-catenin signaling, as well as proliferation, migration, and differentiation in cancer cells, neither dietary supplementation with Vitamin D nor treatment with Vitamin D analogues altered the formation or growth of HCC associated with β-catenin activation. These results conclusively demonstrate the lack of utility of targeting Vitamin D for therapy of HCC in this setting."

Clinical • Journal

Vitamin D pathway activation selectively deactivates signal transducer and activator of transcription (STAT) proteins and inflammatory cytokine production in natural killer leukemic large granular lymphocytes. (PubMed, Cytokine) - "We identified 15 cytokines, including IL-10 and Flt-3L, which were significantly different between normal donors and NK-LGLL patients. Overall, our results suggest that activating the vitamin D pathway could be a mechanism to decrease STAT1 and 3 activation and inflammatory cytokine output in NK-LGLL patients."

Journal

Bifunctional VDR-miR193a Axis Modulates APOL1 Expression in Human Podocytes (KIDNEY WEEK 2019) - "Conclusion Bifunctional VDR-miR193a axis regulates APOL1 regulate APOL1 directly as well as through modulation of WT1. Funding NIDDK Support"

Calcitriol Inhibits the Proliferation of Triple-Negative Breast Cancer Cells through a Mechanism Involving the Proinflammatory Cytokines IL-1β and TNF-α. (PubMed, J Immunol Res) - "Furthermore, the combination of calcitriol with TNF-α resulted in a greater antiproliferative effect than either agent alone, in the two TNBC cell lines and an estrogen receptor-positive cell line. In summary, this study demonstrated that calcitriol exerted its antiproliferative effects in part by inducing the synthesis of IL-1β and TNF-α through IL-1R1 and TNFR1, respectively, in TNBC cells, highlighting immunomodulatory and antiproliferative functions of calcitriol in TNBC tumors."

Journal

Effects of vitamin D3 and its chemical analogs on the growth of Hodgkin's lymphoma, in vitro. (PubMed, BMC Res Notes) - "nuVDR for DMSO control and VD3 was comparable. These results suggest that VD3 or VDAs may affect growth of HL."

Journal • Preclinical

The Synthetic Vitamin D Analog EB1089 Restricts Adrenocortical Tumor Proliferation in NCI-H295 Xenograft Model (ENDO 2019) - "The activation of VDR signaling by EB1089 inhibited B-catenin activated ACT proliferation. Furthermore, in vivo, EB1089 reduced tumor steroid secretion and did not result in important VD side effects like significant hypercalcemia and weight loss. VD analogs have antitumor activity and may emerge as an adjuvant therapy for patients with ACT.*Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation."

Preclinical

The Synthetic Vitamin D Analog EB1089 Restricts Adrenocortical Tumor Proliferation in NCI-H295 Xenograft Model (ENDO 2019) - "The activation of VDR signaling by EB1089 inhibited B-catenin activated ACT proliferation. Furthermore, in vivo, EB1089 reduced tumor steroid secretion and did not result in important VD side effects like significant hypercalcemia and weight loss. VD analogs have antitumor activity and may emerge as an adjuvant therapy for patients with ACT."

Preclinical