| Features: | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 3BP, a small molecule, results in a remarkable therapeutic effect when it comes to treating cancers exhibiting a "Warburg effect." 3-Bromopyruvate — also written as 3BP or 3-BrPA — is a small, highly electrophilic pyruvate/lactate analog that acts as a metabolism-targeting alkylating agent (covalently modifying protein thiols) and is widely studied as an experimental anticancer compound. Functionally, it is best classified as a metabolic poison / anti-metabolite with multi-target effects centered on rapid ATP collapse (glycolysis + mitochondrial metabolism) and secondary oxidative and cell-death signaling. Cancer selectivity is often framed as higher uptake via MCT1 and higher reliance on glycolysis/Warburg metabolism, but the same chemical reactivity underlies a narrow safety margin unless formulated/delivered carefully. Primary mechanisms (ranked):
Bioavailability / PK relevance: Unformulated 3BP is chemically reactive and can be systemically toxic; practical translation has focused on formulation (e.g., cyclodextrin/microencapsulation) and/or locoregional delivery to improve tolerability and tumor exposure. Uptake can depend on transporter context (e.g., MCT1 expression) and extracellular pH/lactate milieu (context-dependent). In-vitro vs systemic exposure relevance: Many in-vitro studies use µM–mM ranges; higher (mM) conditions may exceed what is plausibly achievable systemically without toxicity. Reported activity at low µM exists in some models (especially with optimized derivatives/formulations), but exposure/target-engagement in humans remains the central constraint. Clinical evidence status: Not an approved drug. Evidence is predominantly preclinical (cell/animal). Human use has been limited and controversial, including safety incidents reported in non-standard clinical settings. A 3BP-derived clinical agent (e.g., KAT/3BP / KAT-101) is in early-phase clinical testing (HCC), but that is distinct from generic/unformulated 3BP. Overall, 3BP attacks cancer cells by “starving” them of energy, leading to energetic collapse, oxidative damage, and eventual cell death.- 3BP is known to inhibit enzymes involved in glycolysis, such as hexokinase II (HKII). Many cancer cells overexpress HKII and rely on glycolysis for ATP production. Inhibiting HKII leads to decreased ATP levels and energy depletion. - Fermentation inhibitor:(inhibits conversion of pyruvate to lactate) NAD+ is compromised slowing Glycolysis leading to reduced ATP - By depleting ATP, 3BP can impair mitochondrial functions indirectly. - LDH converts pyruvate to lactate. In many cancers, lactate production is high (the Warburg effect). Inhibition of LDH disrupts lactate production and may contribute to an intracellular buildup of toxic metabolites. - There is evidence indicating that, by interfering with glycolysis, 3BP might also indirectly affect the PPP. This reduces the production of NADPH, weakening the cancer cell’s ability to manage oxidative stress. - Impairing energy metabolism, 3BP can indirectly affect mitochondrial function, potentially leading to an increase in ROS production. Although 3BP shows promise as a metabolic inhibitor with anticancer properties, its transition from preclinical studies to approved clinical therapy has not yet been realized. -Combining metabolic inhibitors like 3BP with agents that modulate ROS levels could represent a synergistic approach in cancer therapy. By simultaneously disrupting energy production and exacerbating oxidative stress, such combinations may more effectively induce cancer cell death while sparing normal cells. In advanced cancer it has been known to kill the cancer too fast, causing liver failure and death. 3-Bromopyruvate (3BP, 3-BrPA) — mechanistic axes (oncology)
|
| Source: HalifaxProj(promote) |
| Type: |
| Natural Killer (NK) cells are a type of lymphocyte in the immune system that play a crucial role in the body's defense against tumors and virally infected cells. NK cells can directly kill cancer cells through the release of cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and induce apoptosis (programmed cell death). NK cells produce various cytokines, such as interferon-gamma (IFN-γ), which can enhance the immune response and promote the activation of other immune cells, including macrophages and T cells. -Monoclonal Antibodies: Using antibodies that engage NK cells to target and kill cancer cells. -Cytokine Therapy: Administering cytokines like IL-2 or IL-15 to boost NK cell activity. |
| 5269- | 3BP, | The anti-metabolite KAT/3BP has in vitro and in vivo anti-tumor activity in lymphoma models. |
| - | in-vitro, | HCC, | NA |
| 5265- | 3BP, | KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas |
| - | Review, | lymphoma, | 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#:20 Target#:219 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid