Thiolutin

Thiolutin (Acetopyrrothin) is a sulfur-containing antibiotic, which is a potent inhibitor of bacterial and yeast RNA polymerases. Thiolutin can be produced by Streptomyces. Thiolutin inhibits AMSH (IC₅₀ = 4 μM) and Rpn11 (IC₅₀ = 0.53 μM). Thiolutin is a dual inhibitor of BRCC36 and the NLRP3 inflammasome, exhibiting anti-inflammatory effects. Thiolutin effectively suppresses the interaction between BRCC36 and HMGCR, leading to the inhibition of HCC growth. Thiolutin attenuates pyroptosis and NLRP3 inflammasome activation. Thiolutin markedly alleviates renal injury and inflammatory process in IgAN. Thiolutin is an anti-angiogenic compound which can ease Doxorubicin-induced cardiotoxicity (DOXIC)^{[1][2][3][4][5]}. In Vitro:

Thiolutin (0.5-2 μM, 24 h) significantly inhibits the expression of BRCC36 and HMGCR proteins in a dose-dependent manner in HepG2 and Hep3B cells^[1].

Thiolutin (0-24 h) attenuates the interaction between HMGCR and BRCC36 in HepG2 cells and reduces the half-life of the HMGCR protein while increasing its ubiquitination level in both HepG2 and Hep3B cells^[1].

Thiolutin (0.1-10 μM, 48 h) inhibits the proliferation of HepG2 and Hep3B cells dose-dependently^[1].

Thiolutin (0.25-0.5 μM, 14 days) elevates RSL3 (HY-100218A)-induced cell death and RSL3-triggered lipid peroxidation in HepG2 cells^[1].

Thiolutin (25-250 nM) inhibits the LDH release induced by LPS (HY-D1056) and Nigericin (HY-127019)^[1].

Thiolutin (0.5 μM, 14 days) reduces the colony-forming ability of HepG2 cancer cells in the presence of Lovastatin (HY-N0504) (5 μM)^[1].

Thiolutin (50 μM, 0-120 min) induces global transcriptional stress in Neurospora^[2].

Thiolutin (50 μM, 1-4 h) inhibits protein degradation by the proteasome in N.crassa and HeLa cells^[2].

Thiolutin (0.001-100 μM) inhibits AMSH with an IC₅₀ of 4 μM, which is higher than its inhibition of Rpn11 (IC₅₀ = 0.53 μM), and this effect is reversible by Zn(cyclen)²⁺^[2].

Thiolutin (10-50 nM, 30 min) attenuates pyroptosis and NLRP3 inflammasome activation in J774 A.1 murine monocyte-macrophage cells^[3].

Thiolutin (0.75 mg/kg, i.p., every 3 days for 18 days) significantly decreases the volume and weight of the tumor in the BALB/c or C57 mice subcutaneously injected with 0.1 mL of PBS containing SMMC7721, HepG2, or Heap1-6 cells^[1].

Thiolutin (0.5-5 mg/kg, i.p., every 2 days for 4 weeks) alleviates kidney injury, attenuates renal inflammation and modulates the NLRP3 inflammasome pathway in IgAN mice without hepatotoxic effects^[3].

Thiolutin (1 mg/kg, i.p., once daily for 4 weeks ) improves cardiac function, mitigates cardiac remodeling urged by Doxorubicin (DOX) and restrains the NLRP3 inflammasome activation in DOX‑challenged mice^[4].