Triptonide

• CAS: 38647-11-9
• Catalog Number: ACM38647119-1
• Category: Main Products
• Molecular Weight: 358.39
• Molecular Formula: C20H22O6
• Synonyms: TRIPTONIDE;TRIPTONIDE(PRIMARY STANDARD);(3bS,4aS,5aS,6aS,7aS,7bS,8aS,8bS)-6a-Isopropyl-8b-methyl-3b,4,4a,7a,7b,8b,9,10-octahydrotrisoxireno[4b,5:6,7:8a,9]phenanthro[1,2-c]furan-1,6(3H,6aH)-dione;14-Deoxy-14-oxotriptolide;Triptolide,14-deoxy-14-oxo;NSC 165677;PG 492
• IUPAC Name: Triptonide
• SMILES: CC(C)C12C(O1)C3C4(O3)C5(CCC6=C(C5CC7C4(C2=O)O7)COC6=O)C
• InChI: InChI=1S/C20H22O6/c1-8(2)18-13(25-18)14-20(26-14)17(3)5-4-9-10(7-23-15(9)21)11(17)6-12-19(20,24-12)16(18)22/h8,11-14H,4-7H2,1-3H3/t11-,12-,13-,14-,17-,18-,19+,20+/m0/s1
• InChI Key: SWOVVKGLGOOUKI-ZHGGVEMFSA-N
• Boiling Point: 581.1ºC at 760 mmHg
• Flash Point: 257.8ºC
• Density: 1.48 g/cm³
• Appearance: White-beige powder
• Exact Mass: 358.14200

Case Study

Triptonide for the Inhibition of Ovarian Cancer via p38/p53 Pathway Activation and Lethal Autophagy Induction

Lou R, et al. Bioorganic & Medicinal Chemistry, 2024, 110, 117788.

In a targeted investigation of anti-ovarian cancer agents, triptonide-isolated from Tripterygium wilfordii-was evaluated for its potent cytotoxicity against A2780 ovarian cancer cells. The IC50 was determined to be 2.972 nM via MTT assays. Flow cytometry analysis revealed triptonide-induced apoptosis, with mechanistic studies confirming activation of the p38 MAPK/p53 signaling cascade. Western blotting further validated upregulation of phosphorylated p38 and p53 proteins post-treatment. Cell cycle analysis via propidium iodide staining showed S-phase arrest. Moreover, triptonide triggered lethal autophagy, evidenced by increased LC3-II levels, detected through immunoblotting, and punctate LC3 accumulation observed by immunofluorescence microscopy. In vivo, xenograft models treated with triptonide exhibited significant tumor growth inhibition without apparent toxicity. Collectively, the experimental outcomes establish triptonide as a dual-action agent, simultaneously inducing apoptosis and autophagy, positioning it as a promising therapeutic candidate for ovarian cancer management.

Triptonide for Targeting Hedgehog/FLT3 Signaling in FLT3-ITD-Driven Acute Myeloid Leukemia

Xu Y, et al. Biomedicine & Pharmacotherapy, 2021, 133, 111054.

Triptonide demonstrates potent anti-leukemic activity against FLT3-ITD-positive acute myeloid leukemia (AML) by targeting the Hedgehog/FLT3 signaling axis. In vitro, nanomolar concentrations of triptonide induced apoptosis and G0/G1 cell cycle arrest in FLT3-ITD AML cells. Experimental methods involved treating FLT3-ITD leukemia cell lines with varying doses of triptonide, followed by flow cytometry to assess apoptosis and cell cycle phases. Western blot analyses confirmed the downregulation of GLI2, c-Myc, and FLT3, alongside p53 upregulation. In vivo, an orthotopic mouse model was employed, where triptonide was administered to evaluate its therapeutic efficacy. Treatment significantly reduced leukemic burden and extended survival without observable toxicity. These findings establish triptonide as a promising lead compound capable of selectively disrupting Hedgehog/FLT3 signaling in FLT3-ITD AML, offering a novel therapeutic strategy against this aggressive leukemia subtype.

Activation of the Hippo Pathway for Melanoma Suppression Using Triptonide

Tan S, et al. Biochemical Pharmacology, 2021, 185, 114423.

Triptonide was experimentally applied to suppress melanoma cell metastasis via targeted activation of the tumor-suppressive Hippo pathway. In vitro, melanoma cells were treated with triptonide (MW 358 Da), resulting in robust inhibition of cell tumorigenicity, migration, and invasion, as assessed by proliferation assays, wound healing, and transwell invasion assays. In vivo, tumor-bearing mice received systemic triptonide treatment, leading to significantly reduced tumor growth and lung metastasis with minimal toxicity. Mechanistic studies via Western blotting and immunofluorescence demonstrated that triptonide upregulated SAV1 and LATS1 expression, activated the Hippo pathway, and induced lysosomal degradation of oncogenic YAP. Moreover, MITF expression was diminished, and AKT phosphorylation was suppressed. This comprehensive experimental approach positions triptonide as a potent modulator of Hippo signaling, offering a novel strategy for combating metastatic melanoma through targeted molecular intervention.

Triptonide for the Modulation of Gastric Cancer-Associated Fibroblast Pathological Functions

Wang Z, et al. Biomedicine & Pharmacotherapy, 2017, 96, 757-767.

Triptonide was experimentally applied to inhibit the tumor-promoting functions of gastric cancer-associated fibroblasts (GCAFs). Primary GCAFs and paired gastric normal fibroblasts (GNFs) were isolated from resected patient tissues. In co-culture assays, GCAFs exhibited elevated promotion of gastric cancer cell colony formation, migration, and invasion compared to GNFs. Treatment with triptonide significantly suppressed these GCAF-mediated oncogenic effects. Molecular analysis revealed that triptonide downregulated microRNA-301a and upregulated microRNA-149, restoring their balance and enhancing the secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2) while reducing IL-6 production. Furthermore, triptonide inhibited GCAF-induced epithelial-mesenchymal transition (EMT) in gastric cancer cells. These findings demonstrate the utility of triptonide in modulating the tumor microenvironment through miRNA regulation, positioning it as a potential therapeutic agent targeting fibroblast-mediated cancer progression.

Triptonide for the Induction of Complete Senescence in Acute Myeloid Leukemia Cells

Pan Y, et al. Biochemical Pharmacology, 2017, 126, 34-50.

Triptonide demonstrates potent anti-leukemia activity by inducing complete senescence in acute myeloid leukemia (AML) cells. In vitro, triptonide treatment of U937 and HL-60 AML cell lines resulted in strong growth inhibition and colony suppression, with IC50 values of 7.5 and 12 nM, respectively. In a mouse xenograft model, triptonide (4 mg/kg) achieved over 99% tumorigenicity suppression without evident toxicity. Mechanistically, triptonide downregulated TERT and c-Myc transcription while upregulating senescence markers p16, p21, and pro-apoptotic DDIT3. These molecular effects were mediated via selective activation of the MAPKK3/p38 signaling pathway. The combined transcriptional modulation confirmed triptonide's multi-targeted strategy in promoting senescence followed by apoptosis, positioning it as a promising candidate for AML therapeutics.

Triptonide-Induced Cytotoxicity in Mouse Germ Cells: Exploring lncRNA Obox4-ps35 as a Protective Regulator

Zhang X, et al. Reproductive Toxicology, 2020, 98, 218-224.

In this study, triptonide was experimentally applied to GC2 mouse spermatocyte cells to elucidate its reproductive toxicity mechanisms. Cells were treated with triptonide for 24 hours, followed by assessment of cytotoxicity via cell viability assays, apoptosis detection, and autophagy markers. High-throughput RNA sequencing revealed significant dysregulation of lncRNAs and mRNAs post-treatment. Gene ontology and KEGG analyses highlighted pathways associated with cell death, proliferation, and gene expression regulation. The lncRNA Obox4-ps35 was markedly upregulated, prompting further functional analysis through CRISPR-Cas9-mediated knockout. Obox4-ps35 deficiency exacerbated triptonide-induced apoptosis and autophagy, confirmed by increased apoptotic cell populations and autophagosome formation via fluorescence microscopy. This demonstrates that Obox4-ps35 mitigates triptonide cytotoxicity, suggesting a compensatory cellular response. The study underscores the utility of transcriptomics and gene editing in defining lncRNA-mediated protection against chemical-induced reproductive toxicity.