minnelide / Minneamrita Therap - LARVOL DELTA

Phase II open label trial of Minnelide™ in patients with chemotherapy refractory metastatic pancreatic cancer (AACR 2024) - "The study identified a tolerable drug dose and evidence of activity in a highly chemotherapy-refractory population which provides encouraging proof for the principle of targeting TFIIH in human PDAC."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9 • MYC

Targeting CIC::DUX4 sarcoma with Minnelide in a dual recombinase-initiated genetically engineered mouse model. (PubMed, J Clin Invest) - "Minnelide demonstrated in vivo efficacy in dFLEx CDS GEMMs and in human CDS xenografts. As Minnelide has already been demonstrated to be safe in clinical trials, these findings nominate Minnelide as a potential therapeutic option to test in CDS patients."

Journal • Preclinical • Genetic Disorders • Oncology • Sarcoma • Solid Tumor • DUX4

Pharmacologic reprogramming of virus-tumor crosstalk enhances measles virus antitumor activity in BRAF mutant colorectal cancer models. (PubMed, J Exp Clin Cancer Res) - "Triptolide and Minnelide significantly enhance the oncolytic efficacy of measles virus in colorectal cancer, particularly in BRAF-mutant tumors in vivo, through reprogramming of virus-tumor-stromal interactions. This reprogramming arises from coordinated modulation of survival, metabolic, and stromal signaling pathways and is accompanied by improved intratumoral viral distribution. These findings position virus-tumor-stromal crosstalk as a central mechanistic axis of virotherapy response and provide a strong rationale for the translational and clinical development of rational virus-drug combination strategies in colorectal cancer and other malignancies."

IO biomarker • Journal • Preclinical • Colorectal Cancer • Infectious Disease • Measles • Oncology • Solid Tumor • BRAF • CD31 • CD46 • PECAM1

Triptolide: A Narrative Review of Its Traditional Use, Derivatives, Pharmacology, Antitumor Effect, and Clinical Applications. (PubMed, Cancers (Basel)) - "Finally, we searched clinical trial databases across three platforms for tumors and concluded that Minnelide has strong clinical potential for solid tumors. By critically evaluating TPL from multiple dimensions, specifically its traditional use, chemical derivatization, pharmacokinetics, antitumor mechanisms, toxicity, and clinical trials, this review aims to inform future strategies that maximize therapeutic efficacy while minimizing adverse effects."

Journal • Review • Brain Cancer • Gastric Cancer • Glioma • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Ophthalmology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation

Minnelide enhances the antitumor activity of pan-KRAS inhibitor RMC-6236 in preclinical models for pancreatic cancer (AACR 2026) - "Taken together, these results demonstrate that triptolide/Minnelide augments the activity of RMC-6236 in vitro and in vivo, supporting further preclinical and potentially clinical evaluation. (This work was supported by Minneamrita Therapeutics, Purple Pansies, and the Pancreas National Advisory Council)"

Preclinical • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • MYC

Designing targeted approaches for recurrent medulloblastoma (AACR 2024) - "Additionally, to further support the translational relevance of our data, Minnelide increased the efficacy of adjuvant therapeutics used in the clinical management of MB. Our findings not only highlight the potential for repurposing Minnelide to treat children with recurrent MB, but also the potential of our research approaches aimed at identifying novel therapeutics for relapsed cancers."

Brain Cancer • Medulloblastoma • Oncology • Solid Tumor

Phase II study of Minnelide for patients with adenosquamous carcinoma of the pancreas (ASCP) (AACR 2025) - "In summary, at interim analysis, Minnelide treatment at this lower dose did not meet the efficacy endpoint for study continuation in participants with this difficult to treat variant of pancreatic cancer. Further testing at 2.5mg or higher doses may be warranted."

Clinical • P2 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CTCs • MYC

Minnelide as a potential treatment strategy for CIC::DUX4 sarcoma (AACR 2025) - "Therapeutic advancements for CIC::DUX4 sarcoma have been limited to date, and there are currently no clinical trials available for CDS patients. Our findings demonstrate that Minnelide effectively reduces CDS cell viability and xenograft growth, while downregulating key CIC::DUX4 target genes. Given the role of CIC::DUX4 as a potent transcriptional activator, Minnelide's disruption of this activation may offer a promising therapeutic approach for CDS."

Ewing Sarcoma • Gastric Cancer • Oncology • Sarcoma • Solid Tumor • DUSP6 • DUX4 • ETV1

Triptolide Triggers Protective Autophagy via ROS Induction in NSCLC: Therapeutic Synergy with Autophagy Inhibition. (PubMed, Cancers (Basel)) - "Its water-soluble prodrug, minnelide, is currently undergoing clinical trials for the treatment of pancreatic cancer...Notably, in vivo experiments showed that co-administration of TPL with the autophagy inhibitor chloroquine resulted in significantly stronger tumor growth suppression than either treatment alone. Autophagy acts as a resistance mechanism against TPL-induced cytotoxicity in NSCLC, and pharmacological autophagy inhibition potentiates the antitumor activity of TPL. These findings clarify the ROS-autophagy interplay underlying TPL-mediated cell death and provide a preclinical rationale for combining TPL with autophagy inhibitors as a therapeutic strategy for NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ophthalmology • Pancreatic Cancer • Solid Tumor

Integrating Structural, Biochemical, and Cellular Perspectives on the TFIIH Helicases XPB and XPD. (PubMed, Biomolecules) - "Recent biochemical and pharmacological advances have further revealed the therapeutic relevance of these helicases-XPB as a target of small-molecule inhibitors such as triptolide, Minnelide, and spironolactone, and XPD as a potential modulator of cancer sensitivity to DNA-damaging treatments. Collectively, XPB and XPD exemplify the structural and functional versatility of TFIIH helicases across repair, transcription, and genome maintenance."

Journal • Review • Genetic Disorders • Metabolic Disorders • Oncology • ERCC2 • ERCC3

NCI-2021-12558: Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: City of Hope Medical Center | Recruiting ➔ Active, not recruiting | N=30 ➔ 8

Enrollment change • Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Minnelide ameliorates Col4a5+/- mice by upregulating Col4a5 and alleviating endoplasmic reticulum stress. (PubMed, Front Pharmacol) - "Col4a5 knockdown directly induced ER stress, which was reversed by triptolide treatment. Minnelide demonstrates potent renoprotective effects in AS by upregulating Col4a5 expression and mitigating podocyte ER stress, positioning it as a novel therapeutic candidate."

Journal • Preclinical • Genetic Disorders • Ophthalmology • Renal Disease • COL4A5

From immunosuppression to immune reprogramming: is triptolide a potential "immune reset" agent in autoimmune diseases? (PubMed, Immunol Res) - "We systematically evaluate the most promising candidates (e.g., LLDT-8, Minnelide, ZT01), not only examining their mechanisms but also analyzing why most stall in early development. By integrating mechanistic insights with clinical progress data, we dissect the structural determinants of toxicity and efficacy and propose a concrete future roadmap focused on rational drug design (e.g., novel targets like TAK1), targeted delivery systems, and biomarker-driven precision medicine to advance safe and effective triptolide-based therapies to the clinic."

Journal • Review • Immunology • Ophthalmology

Efficacy of Minnelide in a Next-Generation Dual-Recombinase Regulated Genetically Engineered Mouse Model of CIC::DUX4 Sarcoma. (PubMed, bioRxiv) - "Minnelide demonstrated in vivo efficacy in autochthonous dFLEx CDS GEMMs and in human CDS xenografts. As Minnelide has already been demonstrated to be safe in clinical trials with activity for adult cancers, these findings nominate Minnelide as a novel therapeutic option to test in CDS patients."

Journal • Preclinical • Genetic Disorders • Oncology • Sarcoma • Solid Tumor • DUX4

MINNELIDE IS A NOVEL THERAPEUTIC INHIBITOR OF CIC::DUX4 SARCOMA (CTOS 2025) - No abstract available

Oncology • Sarcoma • Solid Tumor • DUX4

Recent Advances and Challenges in the Treatment of Advanced Pancreatic Cancer: An Update on Completed and Ongoing Clinical Trials. (PubMed, Cancers (Basel)) - "This includes adagrasib (a KRAS inhibitor), olaparib (a PARP inhibitor for BRCA mutations), APG-1387 (an IAP antagonist), minnelide (an anti-stromal agent), arimastat (an MMP inhibitor), MK-0646 (an IGF1R inhibitor), sirolimus (an mTOR inhibitor), and metabolic inhibitors. Furthermore, we have summarized novel approaches such as cancer vaccines and ablation techniques as emerging strategies in the treatment of advanced pancreatic cancer. We have also examined the challenges in treating advanced pancreatic cancer and the factors contributing to therapeutic failure, which may offer valuable insights for developing more effective treatment strategies and innovative drug designs."

Journal • Review • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRCA • KRAS

Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP) (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2026 ➔ Mar 2025 | Active, not recruiting ➔ Completed | Trial primary completion date: Sep 2026 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Cancer

Anti-SARS-CoV-2 and anticancer properties of triptolide and its derived carbonized nanomaterials. (PubMed, Cancer Lett) - "Finally, we showed that triptolide-derived carbonized materials excelled in their anticancer properties compared to triptolide and Minnelide, a water-soluble analog of triptolide. Together, our results provide a rationale for the potential development of triptolide-carbonized derivatives as a promising antiviral candidate for the current pandemic and future outbreaks, as well as anticancer agents."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Ophthalmology • Respiratory Diseases

NCI-2021-12558: Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Oct 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP) (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=11 ➔ 15

Enrollment change • Hepatology • Oncology • Pancreatic Cancer

Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP) (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=55 ➔ 11

Enrollment change • Enrollment closed • Hepatology • Oncology • Pancreatic Cancer

Super-enhancers and efficacy of triptolide in small cell carcinoma of the ovary hypercalcemic type. (PubMed, iScience) - "In patient-derived xenograft models, triptolide and prodrug minnelide effectively inhibit tumor growth. These results reveal unique features of super-enhancers in SCCOHT, which may be one mechanism through which triptolide has high activity in these tumors."

Journal • Oncology • Ovarian Cancer • Solid Tumor • SALL4 • SMARCA2 • SMARCA4

Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Early-phase clinical trials of Minnelide, a water-soluble derivative of triptolide, are promising, but additional work is necessary to optimize dosing, delivery, and safety. This comprehensive analysis demonstrates that triptolide may constitute a repurposed precision medicine tool to overcome tolerance in cancer therapy."

Journal • Review • Breast Cancer • Lung Cancer • Oncology • Ophthalmology • Pancreatic Cancer • Solid Tumor • CDC37 • HSP90AA1 • PARP1

INVESTIGATING THE THERAPEUTIC POTENTIAL OF TRIPTOLIDE PRODRUG, MINNELIDE, AS A TREATMENT ALTERNATIVE FOR CIC-DUX4 SARCOMA (CTOS 2024) - "To date, therapeutic advancements for CIC::DUX4 sarcoma have been limited. Utilizing a high-throughput approach, we screened the effects of 160 epigenetic compounds on human CDS cells and identified triptolide as a top candidate. Our studies demonstrate that treatment with the Triptolide prodrug, Minnelide, significantly reduces CDS cell viability and CDS xenograft growth."

Breast Cancer • Ewing Sarcoma • Gastric Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • CHEK2 • DUSP6 • DUX4 • ETV1 • EWSR1

The Yin and Yang of the Natural Product Triptolide and Its Interactions with XPB, an Essential Protein for Gene Expression and DNA Repair. (PubMed, Genes (Basel)) - "Recent developments, including triptolide prodrugs such as Minnelide and derivatives like glutriptolides, aim to enhance its pharmacokinetic properties and reduce toxicity. This review critically examines triptolide's chemical structure, therapeutic applications, toxicological profile, and molecular interactions with XPB and other protein targets to inform future strategies that maximize therapeutic efficacy while minimizing adverse effects."

Journal • Review • Cardiovascular • Hepatology • Immunology • Oncology • Ophthalmology