tcsc2929 Valrubicin

Valrubicin is a chemotherapy agent, inhibits TPA- and PDBu-induced PKC activation with IC₅₀s of 0.85 and 1.25 μM, respectively, and has antitumor and antiinflammatory activity.

IC50 & Target: IC50: 0.85 μM (TPA-activated PKC), 1.25 μM (PDBu-activated PKC)^[1]

In Vitro: Valrubicin (AD 32) is a chemotherapy agent, inhibits TPA- and PDBu-induced PKC activation with IC₅₀s of 0.85 and 1.25 μM, respectively. Valrubicin inhibits the binding of [³H]PDBu to PKC. Therefore, Valrubicin competes with the tumor promoter for the PKC binding site and prevents the latter from both interacting with the phospholipid and binding to PKC^[1]. Valrubicin shows cytotoxic activity against squamous cell carcinoma (SCC) cell line colony formation, with IC₅₀s and IC₉₀s of 8.24 ± 1.60 μM and 14.81 ± 2.82 μM for UMSCC5 cells, 15.90 ± 0.90 μM, 29.84 ± 0.84 μM for UMSCC5/CDDP‡ cells, and 10.50 ± 2.39 μM, 19.00 ± 3.91 μM for UMSCC10b cells, respectively. Moreover, Valrubicin in combination with radiation enhances the cytotoxicity^[2].

In Vivo: Valrubicin (3, 6, or 9 mg) reduces tumor growth at week 3 by intratumoral jection in hamster. Valrubicin (6 mg) combined with minimally cytotoxic irradiation (150, 250, or 350 cGy) causes significant tumor shrinkage in hamster^[2]. Valrubicin (0.1 μg/μL) significantly reduces the number of infiltrating neutrophils in biopsies challenged with TPA at 24 h and attenuates chronic inflammation in mice. Valrubicin also decreases the expression levels of inflammatory cytokines in the acute model^[3].