| Features: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
| Source: |
| Type: protein |
| Manganese superoxide dismutase (MnSOD, also known as SOD2). SOD2 (Superoxide Dismutase 2) is a protein that is a member of the superoxide dismutase family of enzymes, which are involved in the detoxification of superoxide radicals. -MnSOD is localized in the mitochondria and plays a key role in detoxifying superoxide radicals, thereby limiting oxidative damage and maintaining mitochondrial integrity. • By modulating ROS levels, MnSOD influences cellular signaling pathways involved in proliferation, apoptosis, and metabolic adaptation—all of which are critical during tumorigenesis. Typically low SOD2 expression in cancers, with poor prognosis. -Increased MnSOD levels may help tumor cells manage the high levels of ROS resulting from rapid cell division and metabolic alterations, which can contribute to tumor progression. - Some prognostic studies associate high levels of MnSOD with resistance to apoptosis and poorer patient outcomes; however, findings are not entirely consistent across all studies. • Depending on the tumor type and the balance with other antioxidant systems, high MnSOD can be associated with either favorable or unfavorable clinical outcomes, reflecting its dual roles in cancer biology. |
| 7164- | CHA, | Chaetocin induces apoptosis in human melanoma cells through the generation of reactive oxygen species and the intrinsic mitochondrial pathway, and exerts its anti-tumor activity in vivo |
| - | vitro+vivo, | Melanoma, | A375 |
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
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:433 Target#:935 State#:% Dir#:1
wNotes=0 sortOrder:rid,rpid