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| 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)
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| Also known as CP32. Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death. As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression. Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy. Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent. On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer. Procaspase-3 is a apoptotic marker protein. Prognostic significance: • High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers. • Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers. |
| 5280- | 3BP, | Anticancer Efficacy of the Metabolic Blocker 3-Bromopyruvate: Specific Molecular Targeting |
| - | in-vitro, | PC, | NA |
| 5277- | 3BP, | 3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model |
| - | in-vivo, | PC, | Panc02 |
| 5271- | 3BP, | The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside |
| - | Review, | Var, | 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
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