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| Formononetin is an O-methylated isoflavone. -Ononin is formononetin-7-O-β-D-glucoside, meaning formononetin with a glucose attached at the 7-position. Found in several plant sources, including: Red Clover (Trifolium pratense): Astragalus membranaceus: Other Leguminous Plants: -Various plants in the legume family (Fabaceae) may also contain formononetin, although the levels and bioavailability can differ depending on the plant species and extraction methods. Pathways: PI3K/Akt Pathway: formononetin may inhibit the phosphorylation of Akt (MAPK) Pathway: may modulate components of the MAPK pathway STAT3 Signaling Pathway: formononetin can downregulate STAT3 activity NF-κB Pathway: modulating NF-κB activation Apoptotic Pathways: via mitochondrial-dependent pathways, enhancing caspase activation Induce cell cycle arrest at different checkpoints (e.g., G1 or G2/M phases) Formononetin, a naturally occurring isoflavone found in red clover, Astragalus membranaceus, and other leguminous plants, shows promise as an anticancer agent. Its ability to modulate key signaling pathways—including PI3K/Akt, MAPK, STAT3, NF-κB, and apoptotic and cell cycle regulatory mechanisms—suggests a multifaceted potential in cancer prevention and therapy. Formononetin — Formononetin is a naturally occurring O-methylated isoflavone and phytoestrogen found primarily in red clover, Astragalus membranaceus, licorice, kudzu, and other Fabaceae plants. It is classified as a plant-derived isoflavonoid small molecule and is commonly abbreviated FMN, FNT, FT, or Form. Formononetin is also produced from its glycoside ononin and is extensively converted in vivo to daidzein and phase-II conjugates. Its anticancer activity remains experimental and is complicated by concentration-dependent estrogen-receptor signaling, limited aqueous solubility, rapid metabolism, and comparatively low systemic exposure to unconjugated parent compound. Primary mechanisms (ranked):
Bioavailability / PK relevance: Native formononetin has poor water solubility, substantial intestinal and hepatic first-pass metabolism, rapid glucuronidation and sulfation, and extensive O-demethylation to daidzein. Rat oral bioavailability has been reported at approximately 22%, but this does not establish comparable human exposure. Free parent formononetin generally represents only a small fraction of circulating total isoflavones. Phospholipid, nanoparticle, lipid, and bioenhancer formulations can increase exposure in animals but are not validated cancer treatments. In-vitro vs systemic exposure relevance: Many anticancer studies use approximately 20–100 µM formononetin, whereas exposure to unconjugated parent compound after ordinary oral red-clover or dietary-isoflavone intake is generally much lower. Consequently, many direct cytotoxic, ROS-generating, STAT-inhibitory, and apoptosis-inducing findings occur at concentrations unlikely to be achieved systemically with conventional oral preparations. Lower concentrations may instead produce estrogenic or proliferative effects in ERα-positive cells, creating a clinically important biphasic-response concern. Clinical evidence status: Preclinical. Evidence includes cancer-cell experiments and multiple murine xenograft or carcinogenesis models. No established formononetin monotherapy or adjunctive cancer regimen is supported by completed randomized clinical trials, and formononetin is not an approved anticancer drug. Human trials involving red-clover isoflavone mixtures address menopausal, vascular, or bone outcomes rather than cancer treatment and cannot be attributed specifically to formononetin. Safety considerations: Human safety data for purified formononetin are limited. Its ERα agonist and phytoestrogen properties warrant caution in estrogen-sensitive malignancies and in patients using endocrine therapies. Experimental studies demonstrate concentration-dependent stimulation of ERα-positive breast-cancer cells at low micromolar concentrations and inhibition at higher concentrations. Potential interactions may also arise through drug-efflux transporters, CYP enzymes, glucuronidation pathways, anticoagulant drugs, or combination chemotherapy. Long-term reproductive, endocrine, hepatic, and oncologic safety of pharmacological-dose purified formononetin remains unresolved. Formononetin Mechanistic Profile
P: 0–30 min R: 30 min–3 hr G: >3 hr |
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| Bach1 (BTB and CNC homology 1) is a protein involved in the regulation of gene expression, specifically through the control of the stability and translation of messenger RNA (mRNA). Bach1 has been found to be overexpressed in several types of cancer, including lung, breast, and prostate cancer. High levels of Bach1 have been associated with increased cancer cell proliferation, migration, and invasion, as well as reduced sensitivity to chemotherapy. |
| 6981- | Form, | Formononetin: a review of its source, pharmacology, drug combination, toxicity, derivatives, and drug delivery systems |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | PSA, | NA |
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#:274 Target#:647 State#:% Dir#:1
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