We demonstrated that NCI-41356 was able to disrupt the nuclear interaction of HSPB5 and SMAD4 in a fibrotic context, thus limiting the translocation of SMAD4 and his partner pSMAD3 into the nucleus and leading to the inhibition of TGF-β1 signaling in vitro and lung fibrosis in vivo. The gene discussed is SMAD4; the disease is pulmonary fibrosis.