dimethylamino micheliolide (ACT001)

P3, N=270, Not yet recruiting, Affiliated Cancer Hospital of Shandong First Medical University (Shandong Institute of Cancer Prevention and Treatment and Shandong Cancer Hospital);

P2, N=60, Recruiting, Nationwide Children's Hospital | Active, not recruiting --> Recruiting

P2, N=75, Completed, General Hospital of Tianjin Medical University; Tianjin Shangde YaoYuan Technology Co., Ltd | Not yet recruiting --> Completed

ACT001 exhibits antitumoral and immunomodulatory potential by targeting STAT1/STAT3 and regulating PD-L1, offering a promising therapeutic approach for NSCLC.

P2, N=60, Active, not recruiting, Nationwide Children's Hospital | Not yet recruiting --> Active, not recruiting

The orphan drug ACT001, as the SL derivative, has been used in the treatment of glioma, which demonstrated significant potential for the development of such compounds...Furthermore, the orthotopic glioma model using live animal fluorescence imaging demonstrated the therapeutic effect of 1e on MG in vivo and pharmacokinetic studies indicated 1e with a favorable pharmacokinetic profile. Moreover, we performed competitive activity-based protein profiling (ABPP) to explore the potential targets of SL derivatives in U87 cells, providing a basis for the follow-up studies of MG.

P1, N=40, Completed, Accendatech AU Pty Ltd | Recruiting --> Completed

P1, N=21, Completed, Accendatech AU Pty Ltd | Recruiting --> Completed

Focusing on the MDK/c-Myc complex could be an effective approach to combat resistance to TMZ in glioma. Therapy with ACT001 may be a novel approach to improve the efficacy of TMZ-based chemotherapy in patients with glioma. Further preclinical and clinical studies are warranted to validate the therapeutic potential of targeting the MDK/c-Myc complex in glioma treatment.

Moreover, ACT001, an orphan drug to treat glioblastoma, disrupts this feed-forward activation loop by inhibiting the STING→NF-κB pathway in microglia, thereby alleviating EAE. These findings emphasize the importance of interactions and bi-directional activations between microglia and Th17 in the autoimmune neuroinflammation, and provide rationale for further investigation on ACT001 as therapeutic option for autoimmune inflammatory diseases driven by similar mechanisms.

P2, N=12, Not yet recruiting, National Neuroscience Institute

ACT001 inhibits the malignant progression of SCLC by suppressing lactate production, modulating macrophage polarization, and restraining tumor metastasis through PGK1 targeting.