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| Chaetocin is a fungal secondary metabolite of the epipolythiodioxopiperazine (ETP) class, originally isolated from Chaetomium species. It has potent preclinical anticancer activity through several mechanisms, including inhibition of histone H3K9 methyltransferases such as SUV39H1, reduction of H3K9me3, disruption of thioredoxin/thioredoxin-reductase redox signalling, induction of oxidative stress, inhibition of Hsp90-associated signalling and promotion of apoptosis. Chaetocin can suppress tumour-cell proliferation and stemness and has shown activity in leukemia, glioblastoma, diffuse midline glioma and several solid-tumour models. It can also sensitize cancer cells to apoptosis-inducing agents and radiation. Although frequently described as an SUV39H1 inhibitor, chaetocin is not highly target-selective and its anticancer effects should not be attributed solely to SUV39H1 inhibition. Chaetocin is an experimental fungal metabolite / epigenetic and redox-active anticancer compound, with current therapeutic evidence predominantly preclinical. Chaetocin — a sulfur-rich fungal secondary metabolite of the epipolythiodioxopiperazine (ETP) class originally isolated from Chaetomium species. It is an experimental redox-active and epigenetically active small molecule with potent preclinical anticancer activity. Chaetocin is commonly described as an SUV39H1/KMT1A inhibitor, but this classification is incomplete: it inhibits thioredoxin reductase, produces substantial oxidative stress, covalently perturbs proteins through its reactive disulfide functionality, inhibits multiple histone lysine methyltransferases, disrupts the SUV39H1–HP1 interaction, and can inhibit Hsp90-dependent signaling. It should therefore be classified as a multitarget ETP fungal metabolite / experimental epigenetic-redox anticancer compound rather than as a selective SUV39H1 inhibitor. Primary mechanisms (ranked):
Bioavailability / PK relevance: Human pharmacokinetic parameters, therapeutic plasma concentrations, bioavailability and exposure-response relationships have not been established. Preclinical work indicates unusual intracellular handling related to the intact ETP disulfide groups and cellular redox environment. The highly reactive disulfide pharmacophore, broad protein reactivity and absence of validated human PK are major translational constraints. In-vitro vs systemic exposure relevance: Anticancer potency varies substantially among models, ranging from low-nanomolar effects in some tumor screens to micromolar concentrations in other mechanistic experiments. There is no established human systemic exposure against which these concentrations can be compared. Consequently, even very potent in-vitro observations cannot currently be assumed to represent clinically achievable selective exposure. Normal-cell sparing has been observed in some hematologic and epithelial comparisons, but chaetocin also inhibits normal endothelial-cell proliferation, so tumor selectivity is not established as a general property. Clinical evidence status: Preclinical only. Evidence includes cancer-cell studies, primary patient-derived cells, xenografts and other animal tumor models, with recent work supporting activity in glioblastoma, diffuse midline glioma and cancer stem-cell models. No established human therapeutic trials, randomized clinical evidence or approved adjunct use were identified. Chaetocin remains an experimental research compound and is not an approved anticancer drug. Chaetocin Mechanistic Profile
P: 0–30 min R: 30 min–3 hr G: >3 hr |
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| Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms: 1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion. 2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue. 3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment. 4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream. 5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body. 6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection. 7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs. 8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis. |
| 7181- | CHA, | Chaetocin induces cell cycle arrest and apoptosis by regulating the ROS-mediated ASK-1/JNK signaling pathways |
| 7180- | CHA, | Chaetocin: A review of its anticancer potentials and mechanisms |
| - | Review, | Var, | NA |
| 7177- | CHA, | Chaetocin inhibits the progression of neuroblastoma by targeting JAK2/STAT3 signaling pathway in SH-SY5Y cells |
| - | NA, | neuroblastoma, | SH-SY5Y |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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