dimethylamino micheliolide (ACT001) / Tianjin Suntech Pharma - LARVOL DELTA

The development of ACT001 with Mcl-1 inhibitors as a novel combination therapy for the treatment of paediatric diffuse midline glioma (SNO 2025) - P1 | "Among the strongest were Mcl-1 inhibitors (Mcl1i-MIK665, Mcl1i-AZD5991) consistent with ACT001's mechanism of downregulating anti-apoptotic signaling...In vivo, single-drug treatment of ACT001 or Mcl1i-S63845 extended survival in orthotopic DMG models and significantly reduced the number of Ki67-positive tumor cells...Our findings suggest that ACT001 is a multi-targeted agent acting on NF-κB and apoptotic signalling while inducing oxidative stress. The combination of ACT001 with anti-apoptotic protein inhibitors represents a promising treatment strategy for DMG patients."

Combination therapy • IO biomarker • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Pediatrics • Solid Tumor • BCL2 • NQO1 • SLC7A11 • SOD2

The development of ACT001 with Mcl-1 inhibitors as a novel combination therapy for the treatment of paediatric diffuse midline glioma (WFNOS 2025) - P1 | "Among the strongest were Mcl-1 inhibitors (Mcl1i-MIK665, Mcl1i-AZD5991) consistent with ACT001’s mechanism of downregulating anti-apoptotic signaling...In vivo, single-drug treatment of ACT001 or Mcl1i-S63845 extended survival in orthotopic DMG models and significantly reduced the number of Ki67-positive tumor cells...Our findings suggest that ACT001 is a multi-targeted agent acting on NF-κB and apoptotic signalling while inducing oxidative stress. The combination of ACT001 with anti-apoptotic protein inhibitors represents a promising treatment strategy for DMG patients."

Combination therapy • IO biomarker • Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Pediatrics • Solid Tumor • BCL2 • NQO1 • SLC7A11 • SOD2

ACT001 alleviates MASLD through gut microbiota-bile acid-FXR axis in mice. (PubMed, Ann Med) - "ACT001 exerted a multifactorial therapeutic effect on MASLD, potentially linked to the regulation of the gut microbiota-BAs-FXR axis. Thus, it has the potential to be an effective treatment for MASLD."

Journal • Preclinical • Hepatology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology

A Randomized, Blinded, Placebo-controlled Phase III clinical Trial to Evaluate the Efficacy of ACT001 to Enhance the Result of Radiotherapy and the Reduction of Toxic and Side Effect of whole-Brain Radiotherapy for Patients with Brain Metastasis of Small Cell Lung Cancer (ChiCTR) - P3 | N=270 | Not yet recruiting | Sponsor: Affiliated Cancer Hospital of Shandong First Medical University (Shandong Institute of Cancer Prevention and Treatment and Shandong Cancer Hospital);

Adverse events • IO biomarker • New P3 trial • Brain Cancer • Lung Cancer • Oncology • Solid Tumor

A NOVEL SMALL MOLECULE DRUG ACT001 INHIBITS NEUROBLASTOMA METASTASIS VIA MODULATING THE STAT1/TEAD4/YAP1 AXIS (SIOP 2025) - "Additionally, ACT001 exhibited synergistic effects with etoposide and enhanced NB cell differentiation when combined with RA. ACT001 effectively inhibits NB invasion and metastasis by modulating the STAT1/TEAD4/YAP1 axis and activating the Hippo pathway. Furthermore, ACT001 enhances the efficacy of chemotherapeutic agents and differentiation therapies, showing a promising therapeutic strategy for neuroblastoma."

Neuroblastoma • Solid Tumor • STAT1 • TEAD4 • YAP1

GSDMD-Deficient G-MDSCs Exert Profoundly Suppressive Activity to Relieve MPTP-Induced Parkinson's Disease. (PubMed, CNS Neurosci Ther) - "GSDMD deficiency promotes immunosuppressive G-MDSCs that inhibit neuroinflammation and PD progression. Targeting GSDMD to modulate MDSCs' function represents a novel therapeutic strategy for PD."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • NLRP3

Accendatech’s Phase 3 Trial of ACT001, an Oral Compound with Novel MoA, Begins Enrolling Patients with Small Cell Lung Cancer with Brain Metastasis in a Highly Competitive Research Field (Businesswire)

Enrollment open • Small Cell Lung Cancer

Monocyte-Macrophage Modulation in Radiation-Immunotherapy-Induced Pneumonitis in NSCLC (ASTRO 2025) - "This study highlighted the critical pro-inflammatory role of monocyte-macrophages in RIP and demonstrated that ACT001, by targeting macrophages, mitigated lung injury induced by combined radiotherapy and immunotherapy, without compromising anti-tumor efficacy."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • CCR2 • ITGAM

ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Nationwide Children's Hospital | Active, not recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • High Grade Glioma • Oncology • Solid Tumor

A Randomized, Open, Controlled, Multi-Centre, Phase II Clinical Study to Evaluate the Efficacy and Safety of ACT001 Monotherapy and the Combination of ACT001 with Temozolomide VS Temozolomide or Lomustine Alone in Patients with Recurrent Glioblastoma (ChiCTR) - P2 | N=75 | Completed | Sponsor: General Hospital of Tianjin Medical University; Tianjin Shangde YaoYuan Technology Co., Ltd | Not yet recruiting ➔ Completed

Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

ACT001 Inhibits Tumor Progression and Modulates Immune Responses in Non-Small Cell Lung Cancer. (PubMed, J Clin Lab Anal) - "ACT001 exhibits antitumoral and immunomodulatory potential by targeting STAT1/STAT3 and regulating PD-L1, offering a promising therapeutic approach for NSCLC."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • GZMB • STAT1 • STAT3

ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Nationwide Children's Hospital | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • High Grade Glioma • Oncology • Solid Tumor

Bioactive sesquiterpene lactones from Elephantopus scaber: semi-synthesis, target fishing, anti-malignant glioma efficacy in vitro and in vivo. (PubMed, Eur J Med Chem) - "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."

Journal • Preclinical • Brain Cancer • Glioma • Hepatitis C • High Grade Glioma • Infectious Disease • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • CDH1 • MMP2 • MMP9 • VIM

A study to evaluate the safety,tolerability and pharmacokinetics of ACT001 in children with advanced brain and solid tumors (ANZCTR) - P1 | N=40 | Completed | Sponsor: Accendatech AU Pty Ltd | Recruiting ➔ Completed

Trial completion • Brain Cancer • Glioma • Neutropenia • Solid Tumor

A study to evaluate the safety, tolerability and pharmacokinetics of ACT001 in patients with advanced solid tumors (PART B). (ANZCTR) - P1 | N=21 | Completed | Sponsor: Accendatech AU Pty Ltd | Recruiting ➔ Completed

Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Engineering the cytochrome P450 to enhance parthenolide production in Saccharomyces cerevisiae. (PubMed, Synth Syst Biotechnol) - "Parthenolide is confirmed to be an important component of the anticancer drug-ACT001...Eventually, a parthenolide titer of 99.71 mg/L was achieved in a 5-L bioreactor. Our research provides effective strategies and valuable references for engineering rate-limiting cytochrome P450 enzymes to improve sesquiterpenes production in S. cerevisiae."

Journal • Oncology

Targeting the MDK/c-Myc complex to overcome temozolomide resistance in glioma. (PubMed, Clin Transl Med) - "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."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • Targeted Protein Degradation • MDK • MYC

Targeting microglia-Th17 feed-forward loop to suppress autoimmune neuroinflammation. (PubMed, J Neuroinflammation) - "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."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Immunology • Inflammation • Multiple Sclerosis • Oncology • Solid Tumor • STING

Integrative transcriptomic and metabolomic analysis explores the mechanisms by which ACT001 treats MAFLD in mice. (PubMed, Sci Rep) - "ACT001 may exert a therapeutic effect in MAFLD mice by modulating glutathione metabolism and linoleic acid metabolism. It has the potential to be a promising treatment for MAFLD."

Journal • Preclinical • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease

ACT001 improves OVX-induced osteoporosis by suppressing the NF-κB/NLRP3 signaling pathway. (PubMed, Mol Med) - "Furthermore, ACT001 protected ovariectomy-induced bone loss in mice, reduced the number of osteoclasts, downregulated the expression of NLRP3 and IL-1β. These data indicate that ACT001 can reduce RANKL-induced osteoclast differentiation through suppressing the NF-κB/NLRP3 pathway, and attenuate the bone loss induced by estrogen-deficiency, suggesting its therapeutic potential for bone homeostasis maintenance and osteoporosis treatment."

Journal • Orthopedics • Osteoporosis • Rheumatology • CTSK • IL18 • IL1B • NFATC1 • NLRP3

Nankai University team’s new anti-tumor drug ACT001 is included in the national ’breakthrough therapy’ list [Google translation] (Sina Corp) - "China News Service, Tianjin, February 6...The reporter learned from Nankai University that the new drug candidate ACT001...was recently included in the list of my country's 'breakthrough therapeutic varieties' by the Drug Review Center (CDE) of the State Drug Administration...It is reported that the 'breakthrough therapy product' for small cell lung cancer brain metastases is the most important clinical research qualification obtained by ACT001 at present. The relevant clinical trial is a phase 2b/3 clinical study of the treatment of brain metastases of lung cancer in combination with whole brain radiotherapy..."

Breakthrough therapy • Brain Cancer • Small Cell Lung Cancer

Proof-of-Concept Study of ACT001 in Adult Patients with Recurrent Glioblastoma Harbouring STAT3-High Signature (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: National Neuroscience Institute

New P2 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide. (PubMed, Front Pharmacol) - "These compounds, derived from PTL, have been developed to overcome PTL's instability in acidic and basic conditions and its low solubility. We also explore their potential in targeted and combination therapies, providing a comprehensive overview of their therapeutic mechanisms and highlighting their significance in future cancer treatment strategies."

Journal • Review • Oncology

ACT001 Suppresses the Malignant Progression of Small-Cell Lung Cancer by Inhibiting Lactate Production and Promoting Anti-Tumor Immunity. (PubMed, Thorac Cancer) - "ACT001 inhibits the malignant progression of SCLC by suppressing lactate production, modulating macrophage polarization, and restraining tumor metastasis through PGK1 targeting."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • PGK1

ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Nationwide Children's Hospital

New P2 trial • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Malignant Glioma • Oncology • Solid Tumor