Database Query Results : 3-bromopyruvate, ,

3BP, 3-bromopyruvate: Click to Expand ⟱
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):

  1. Covalent thiol alkylation of energy-metabolism enzymes (notably glycolytic nodes such as HK2 and other thiol-sensitive enzymes) → rapid ATP depletion
  2. Mitochondrial bioenergetic disruption (OXPHOS inhibition, permeability/ΔΨm collapse) → energetic crisis
  3. MCT1-facilitated uptake (context-dependent determinant of sensitivity and “selectivity”)
  4. Oxidative stress induction and redox-buffer depletion (ROS↑; GSH/thiols↓) (secondary but often decisive)
  5. Stress-response execution programs (AMPK activation; apoptosis/autophagy; ferroptosis context-dependent; sensitization to other therapies)

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)

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Glycolysis inhibition via thiol-alkylation of glycolytic enzymes ↓ glycolytic flux; ↓ ATP (often rapid) ↔ to ↓ (model-dependent) P/R Energetic collapse Often framed around HK2, but 3BP is broadly thiol-reactive; glycolysis collapse is a convergent phenotype rather than a single-enzyme story.
2 Mitochondrial bioenergetics disruption ↓ OXPHOS; ↓ ΔΨm; ↑ MPTP (context-dependent) ↔ to ↓ (dose-dependent) P/R ATP depletion + mitochondrial stress Dual hit (glycolysis + mitochondria) is a major reason for potency in high-glycolytic tumors; also a toxicity driver if exposure is systemic.
3 MCT1-dependent uptake ↑ uptake and sensitivity when MCT1-high ↔ (varies by tissue MCT1) P Determinant of selectivity MCT1 has been shown as a key sensitivity node in multiple models; “selectivity” claims are strongest when transporter context is documented.
4 Redox buffering and thiol pool depletion ↓ GSH/thiols; redox crisis ↔ to ↓ (dose-dependent) R/G Lowered antioxidant capacity Because 3BP alkylates thiols, GSH depletion can be both direct and indirect; can amplify downstream death pathways and resistance phenotypes.
5 ROS axis ↑ ROS (often); oxidative damage (context-dependent) ↔ (dose- and context-dependent) R Oxidative stress amplification ROS changes are frequently secondary to mitochondrial disruption + thiol depletion; can be decisive for apoptosis/ferroptosis engagement.
6 AMPK energy-stress signaling ↑ AMPK; ↓ anabolic signaling (context-dependent) ↑ AMPK (protective or adaptive) R Stress adaptation vs death priming Energetic collapse typically triggers AMPK; downstream outcomes depend on baseline metabolic state and co-treatments.
7 Cell-death programs: apoptosis and autophagy ↑ apoptosis; ↑ autophagy (context-dependent) ↔ to ↑ stress responses G Execution of cytotoxicity Multiple reports show mixed death phenotypes; autophagy can be cytoprotective or contribute to death depending on context and timing.
8 Ferroptosis axis ↑ ferroptosis susceptibility (context-dependent) ↔ (context-dependent) G Lipid-peroxidation-driven death Most consistent when redox buffering is weakened and/or combined with agents that tilt iron/lipid-ROS balance.
9 NRF2 axis ↔ (model-dependent; often stress-activated) ↔ (model-dependent) G Adaptive antioxidant response NRF2 behavior varies: oxidative stress can activate NRF2, but thiol-alkylation/redox collapse can also overwhelm defenses; treat as context-dependent.
10 Chemosensitization / radiosensitization ↑ sensitization (context-dependent) ↔ R/G Combination leverage Reported synergy with targeted therapy/chemo/radiation in some models, typically via metabolic stress + redox imbalance.
11 Clinical Translation Constraint Formulation/delivery-limited; systemic toxicity risk Off-target injury risk — Therapeutic index limitation Unformulated 3BP has significant toxicity concerns; translation efforts emphasize formulation (e.g., cyclodextrin/microencapsulation) and/or locoregional strategies and derivatives now entering early clinical trials.


Scientific Papers found: Click to Expand⟱
5269- 3BP,    The anti-metabolite KAT/3BP has in vitro and in vivo anti-tumor activity in lymphoma models.
- in-vitro, HCC, NA
toxicity↑, 3-Bromopyruvate (3BP), a small alkylating agent, acts as an anti-metabolite to vital substrates in cancer metabolism and exhibits antitumor activity across various cancer types, but the unformulated 3BP can cause high toxicity
eff↝, This study explores the efficacy of the 3BP clinical derivative KAT/3BP, currently in phase 1 for patients with hepatocellular carcinoma, in lymphoma models.
eff↑, AT/3BP exhibited synergistic activity when combined with lymphoma therapies, including bendamustine and R-CHOP.
Glycolysis↓, At acidic extracellular pH, 3BP enters cancer cells via monocarboxylic acid-1 (MCT-1) and inhibits glycolysis through hexokinase II (HK-2) covalent modification
HK2↓, with HK-2 inhibition and dissociation from mitochondria, apoptosis-inducing factor (AIF) release, and apoptosis induction (9).
AIF↑,
Apoptosis↑,
NK cell↑, In the latter, tumor growth was in vivo reversed, with an increase in the number of circulating CD4+, CD8+, and NK- cells
toxicity↑, unformulated 3BP administrations are associated with severe toxicities, including deaths (22,23)
toxicity↓, However, improvements have been made in developing novel 3BP formulations based on liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes), perillyl alcohol formulations, and others (12,22,24
Dose↝, KAT-101 and KAT-201 are two clinical 3BP derivatives formulated for oral or intratumoral (IT) administration, respectively (National Cancer Institute Thesaurus Codes C193479 and C193479), now entering the early clinical evaluation of patients with h
AntiTum↑, KAT/3BP has in vivo antitumor activity in a syngeneic mouse model.

5282- 3BP,  Rad,    3-Bromopyruvate-mediated MCT1-dependent metabolic perturbation sensitizes triple negative breast cancer cells to ionizing radiation
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
Glycolysis↓, Metabolomic analyses showed that 3BP causes inhibition of glycolysis
RadioS↑, Overall, MCT1-mediated metabolic perturbation in combination with radiotherapy is shown to be a promising strategy for the treatment of glycolytic tumors such as TNBC, overcoming the selectivity challenges of targeting glycolysis with glucose analogs
eff↑, 3BP is selectively toxic to cells expressing MCT1
GAPDH↓, 3BP inhibits GAPDH but not hexokinase
PPP↑, Pentose phosphate pathway is upregulated in response to 3BP
GSH↓, Glutathione and NADH are depleted at early time points
ECAR↓, prolonged incubation with 20 μM 3BP for 24 h resulted in a statistically significant selective decrease in ECAR

5281- 3BP,    A translational study “case report” on the small molecule “energy blocker” 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside
- Case Report, Var, NA
Glycolysis↓, 3BP targets cancer cells’ energy metabolism, both its high glycolysis (“Warburg Effect”) and mitochondrial oxidative phosphorylation.
mt-OXPHOS↓,
ATP↓, This inhibits/ blocks total energy production leading to a depletion of energy reserves. Moreover, 3BP as an “Energy Blocker”, is very rapid in killing such cells.
selectivity↑, 3BP at its effective concentrations that kill cancer cells has little or no effect on normal cells.
toxicity↝, The results obtained hold promise for 3BP as a future cancer therapeutic without apparent cyto-toxicity when formulated properly.
OS↑, The patient (Fig. 5) was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP.
QoL↑,

5280- 3BP,    Anticancer Efficacy of the Metabolic Blocker 3-Bromopyruvate: Specific Molecular Targeting
- in-vitro, PC, NA
mtDam↑, 3-BromoPyruvate severely damaged mitochondrial integrity which might have severely affected ATP generation in cancer cells.
HK2↓, 3-BP inhibits hexokinase II (HK2) and TGFbeta1 and enhanced active caspase-3 expression in tumor tissues as compared to untreated control.
TGF-β↓,
Casp3↑,
selectivity↑,

5279- 3BP,  Rad,    Abstract 5243: 3-Bromopyruvate in combination with radiation inhibits pancreatic cancer growth by dismantling mitochondria and ATP generation in a preclinical mouse model
- in-vivo, PC, NA
ATP↓, ATP production was severely inhibited in cancer cells treated with same concentration of 3-BP
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme of glycolysis pathway and ATP generation in cancer cells.
RadioS↑, We also observed that 3-BP in combination with low doses of irradiation was more effective in killing cancer cells than 3-BP alone.

5278- 3BP,    The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression
- in-vitro, CRC, HCT116 - in-vitro, CRC, Caco-2 - in-vitro, CRC, SW48
ATP↓, 3-Bromopyruvate (3BP) is a pyruvate analogue with alkylating properties that depletes cellular ATP levels and induces rapid cell death in neoplastic cells with limited cytotoxic effects against normal cells.
TumCD↑,
selectivity↑,
toxicity↓, 3BP treatment led to eradication of tumours of hepatocellular carcinoma cell origin in rats without apparent cytotoxic effects [19]
OS↑, first human case report suggested that 3BP was able to prolong survival in a cancer patient diagnosed with hepatocellular carcinoma in 2012 [19,20].
HK2?, 3BP is able to dissociate and inhibit mitochondrial HKII function, thereby reducing ATP production. 3BP binding also frees up binding sites previously occupied by HKII
Cyt‑c↑, llowing pro-apoptotic molecules (such as BAX and BAD) to promote the release of cytochrome c into the cytosol and induce eventual cell death
eff↑, Raji lymphoma cells grown under hypoxic conditions were more sensitive to 3BP than in normoxia
p‑Akt↑, 3BP induces rapid AKT phosphorylation at residue Thr-308

5277- 3BP,    3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model
- in-vivo, PC, Panc02
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP

5276- 3BP,    A Translational Study 'Case Report' on the Small Molecule 'Energy Blocker' 3-Bromopyruvate (3BP) as a Potent Anticancer Agent: From Bench Side to Bedside(2012)
- Case Report, HCC, NA
Dose↓, The patient was given 9 doses of KAT (200 mg) over a period of 6 months
Remission↑, After treatment, the patient loses cancer and the tissue regenerates from 5% to 30%

5275- 3BP,    3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: Introduction to a special issue
- Review, Var, NA
AntiCan↑, the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent.
HK2↓, reported that HK2 is constitutively overexpressed and that 3BP an inhibitor of this enzyme induces cell death.
OCR↓, this agent was found to inhibit the membrane potential, oxygen consumption, and dehydrogenase activities.

5274- 3BP,    ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1
- in-vitro, PC, NA
eff↑, novel microencapsulated formulation of 3BP (ME3BP-7), which is effective against a variety of PDAC cells in vitro and remains stable in serum.
TumCG↓, Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity.
TumMeta↓,
toxicity↝,
Glycolysis↓, The anticancer effects of 3BP were initially attributed to inhibition of glycolysis (Ganapathy-Kanniappan et al., 2009;
toxicity↓, Our previous work demonstrated that microencapsulation of 3BP reduces its toxicity (Chapiro et al., 2014).
Dose↝, we were only able to reliably deliver multiple doses of the drug intravenously (i.v.), and the number of injections and time periods over which we could administer the drug were limited.

5273- 3BP,    The promising anticancer drug 3-bromopyruvate is metabolized through glutathione conjugation which affects chemoresistance and clinical practice: An evidence-based view
- Review, Var, NA
AntiCan↑, 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect.
ROS↑,
angioG↓,
CSCs↓,
Warburg↓,
GSH↓, Reported decrease in endogenous cellular GSH content upon 3BP treatment was confirmed to be due to the formation of 3BP-GSH complex i
Thiols↓, Being a thiol blocker, 3BP may attack thiol groups in tissues and serum proteins e.g. albumin and GSH.

5272- 3BP,    The efficacy of the anticancer 3-bromopyruvate is potentiated by antimycin and menadione by unbalancing mitochondrial ROS production and disposal in U118 glioblastoma cells
- in-vitro, GBM, U87MG - in-vitro, Nor, HEK293
Glycolysis↓, We used the antiglycolytic 3-bromopyruvate (3BP) as a metabolic modifier to treat U118 glioblastoma cell
ROS↑, ROS generated in mitochondria were enhanced at 30 μM 3BP, possibly by unbalancing their generation and their disposal because of glutathione peroxidase inhibition.
GPx↓,
eff↓, Indeed, the scavenger of mitochondrial superoxide MitoTEMPO counteracted 3BP-induced cyt c release and weakened the potentiating effect of 3BP/
OXPHOS↓, (3BP) is a reactive non-specific drug that can act as a metabolic modifier by interfering with glycolysis and oxidative phosphorylation in cancer cells
HK2↓, The mitochondrial hexokinase-II is the main target since its activity is specifically blocked by the formation of a pyruvinyl adduct after reacting with 3BP at the surface of the outer mitochondrial membrane
ATP↓, In malignant tumour cell lines, 3BP inhibits ATPase activity, reduces ATP levels, and reverses chemoresistance by antagonizing drug efflux by acting on the ATP-binding cassette transporters (
ROS↑, Furthermore, 3BP increases the production of reactive oxygen species (ROS) (Ihrlund et al., 2008; Kim et al., 2008; Macchioni et al., 2011a), induces ER stress,
ER Stress↑,
BioAv↓, Unfortunately, prolonged treatment with the drug reduces ROS levels and confers resistance by inducing regulatory genes that act on antioxidant systems.
Cyt‑c↑, 3BP induces cytochrome c release without triggering an apoptotic cascade in U118 cells
eff↑, The ROS enhancers antimycin and menadione sensitize U118 cells to 3BP

5271- 3BP,    The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside
- Review, Var, NA
selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

1340- 3BP,    Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study
- Review, NA, NA
Glycolysis↓, inhibiting key glycolysis enzymes
HK2↓,
LDH↓,
OXPHOS↓, inhibits mitochondrial oxidative phosphorylation
angioG↓,
H2O2↑, induces hydrogen peroxide generation in cancer cells (oxidative stress effect)
eff↑, Concurrent use of a GSH depletor(paracetamol) with 3BP killed resistant melanoma cells

5267- 3BP,    Targeting Energy Metabolism in Cancer Treatment
- Review, Var, NA
HK2↓, Two HK2 inhibitors have been identified, 2-deoxyglucose (2-DG) and 3-bromopyruvate (3-BP).

5266- 3BP,    3-bromopyruvate-based agent KAT-101
- Review, Var, NA
eff↑, Upon oral administration of 3-BP-based agent KAT-101, the 3-BP derivative, being structurally similar to lactic acid, specifically binds to and enters cancer cells through monocarboxylic acid transporters (MCTs)
Glycolysis↓, KAT-101 interferes with both glycolysis and mitochondrial oxidative phosphorylation (OxPhos), thereby depleting adenosine triphosphate (ATP) levels and thus limits energy supply needed by cancer cells to proliferate.
OXPHOS↓,
ATP↓,
TumCP↓,
Apoptosis↑, This induces cancer cell apoptosis and prevents cancer cell proliferation.
HK2↓, In addition, KAT-101 is able to release mitochondrial-bound hexokinase (HK) II (HK2)
MPT↑, increases the formation of mitochondrial permeability transition pores (MPTPs), which induces apoptosis.
LDH↓, KAT-101 also inhibits a variety of enzymes, including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase (PDHK).
PDH↓,

5265- 3BP,    KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas
- Review, lymphoma, NA
Glycolysis↓, Under acidic extracellular pH, 3BP is transported into cancer cells via monocarboxylate transporter 1 (MCT1), inhibiting glycolysis by covalently modifying hexokinase II (HK2).
HK2↓, HK2 dissociation from mitochondria, release of apoptosis-inducing factor (AIF), and induction of apoptosis
AIF↓,
Apoptosis↑,
NK cell↑, In the latter, tumor regression was accompanied by increased circulating CD4+, CD8+, and NK cells, enhanced tumor-associated macrophage infiltration, and reduced local immunosuppression

5264- 3BP,    Candidate cancer drug suspected after death of three patients at an alternative medicine clinic
- Review, Var, NA
toxicity↑, German police took action on 4 August after two patients from the Netherlands and one from Belgium died shortly after undergoing treatment at the Biological Cancer Centre, run by alternative practitioner Klaus Ross in the town of Brüggen, Germany
Glycolysis↓, It is believed to "starve" tumor cells to death by inhibiting glycolysis, the breakdown of glucose molecules to provide cells with energy.
eff↑, experiments on human cancer cell lines showed that combining another chemotherapeutic with 3BP increased its efficacy.
OS↑, the patient "was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP,
QoL↑,
toxicity↝, Vogl says doctors should "absolutely" not perform systemic infusions, in which the drug circulates through the entire body. "

5263- 3BP,  CET,    3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis
- in-vitro, CRC, DLD1 - NA, NA, HCT116
eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

5261- 3BP,    The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH
- in-vitro, BC, NA
eff↑, Transport of the anti-cancer agent 3-bromopyruvate (3BP) in breast cancer cells is mediated by monocarboxylate transporter (MCT)-1 activated by glycosylated chaperone cluster of differentiation (CD) 147. T
eff↓, The extracellular acidic pH increases the affinity for 3BP uptake enhancing its selective cytotoxic effect in tumour cells.

5260- 3BP,    Systemic Delivery of Microencapsulated 3-Bromopyruvate for the Therapy of Pancreatic Cancer
- in-vivo, PC, NA
TumCG↓, In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal
toxicity↓, In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA.
BioAv↝, It is possible that in the microencapsulated formulation, 3-BrPA, is more bioavailable for uptake into tumor cells and less available to the normal cells that apparently mediate its toxicity
GAPDH↓, 3-Bromopyruvate (3-BrPA), a highly potent small-molecular inhibitor of the enzyme GAPDH, represents the only available antiglycolytic drug candidate that is able to enter cancer cells selectively through the monocarboxylate transporter 1 (MCT1; refs.
toxicity↑, However, due to its alkylating properties, 3-BrPA is associated with significant toxicity when delivered systemically in therapeutic doses, which has impeded the clinical development and use of this drug in patients with cancer
Dose↝, Encapsulation of 3-BrPA in β-CD was achieved by portionwise addition of 3-BrPA (166 mg, 1 mmol/L) to a stirring solution of β-CD (1,836 mg in 30 mL DI water). The resulting solution was sonicated for 1 hour at room temperature and then shaken overnig
ATP↓, ability of microencapsulated 3-BrPA (β-CD-3-BrPA) to achieve dose-dependent ATP depletion and cell death, two human pancreatic cancer cell lines were employed.
eff↑, both PDAC cell lines were more sensitive to the drugs when hypoxic (Fig. 2)
TumCI↓, MiaPaCa-2 and Suit-2 cells showed a reduction in invasion at drug concentrations as low as 12.5 µmol/L.
MMP9↓, marked reduction in the secretion of MMP-9 was detected in both cell lines.
toxicity↓, No organ toxicities or tissue damage was observed in animals treated with β-CD–3-BrPA

5259- 3BP,    Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP
- in-vivo, HCC, NA
ATP↓, Advanced cancers (2-3cm) developed and were treated with the alkylating agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively deplete ATP and induce cell death.
TumCD↑,
toxicity↓, In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence.
eff↑, These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers.
tumCV↓, The chemical agent 3-BrPA depletes ATP stores and inhibits HCC cell viability
Dose↝, administered eight treatments on successive days with 1 ml of 2 mM 3-BrPA, also in 1· PBS, pH 7.5. Injection of 3-BrPA was into the tumor.

5258- 3BP,    3-bromopyruvate: Targets and outcomes
- Review, Var, NA
Glycolysis↓, The pyruvate mimetic 3-bromopyruvate (3-BP) is generally presented as an inhibitor of glycolysis and has shown remarkable efficacy in not only preventing tumor growth, but even eradicating existant tumors in animal studies.
TumCG↓,

5257- 3BP,    Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment
- Review, Var, NA
Glycolysis↓, In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug.
mt-OXPHOS↓, Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells.
HK2↓, The direct inhibition of mitochondrial HK-II isolated from the rabbit liver implanted VX2 tumor via 3-BrPA was demonstrated by Ko et al. [17].
Cyt‑c↑, -BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]
Casp3↓,
Bcl-2↓,
Mcl-1↓,
GAPDH↓, Additionally, GAPDH was found to be inhibited by 3-BrPA in several studies
LDH↓, Recent reports showed 3-BrPA had ability to inhibit post glycolysis targets and other metabolic pathways, such as LDH, PDH, TCA cycle, and glutaminolysis
PDH↓, 3-BrPA was proven to be an inhibitor of PDH [72,73,74],
TCA↓,
GlutaM↓, this inhibition of TCA cycle can lead to the impairment of glutaminolysis due to α-KG generated from glutamine is incorporated into the TCA cycle by IDH and αKD activities
GSH↓, Indeed, a remarkable decrease of reduced glutathione (GSH) level was observed after 3-BrPA treatment in both microorganisms and various tumor cells [53,61,65].
ATP↓, 3-BrPA successfully killed AS-30D hepatocellular carcinoma (HCC) cells via the inhibition of both ATP-producing glycolysis and mitochondrial respiration [17].
mitResp↓,
ROS↑, the increase of ROS and concomitant decrease of GSH were commonly found in 3-BrPA-mediated antitumor studies [53,59,61,64,65,76,77,86,89].
ChemoSen↑, When 3-BrPA was combined with cisplatin or oxaliplatin with non-toxic low-dose, 3-BrPA strikingly enhanced the antiproliferative effects of both platinum drugs in HCT116 cells and resistant p53-deficient HCT116 cells [89].
toxicity↝, Finally, two years after the first diagnosis, the patient died due to an overload of liver function rather than the tumor itself [118].

1341- 3BP,    The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate
- Review, NA, NA
Glycolysis↓, second-generation glycolysis inhibitor.
OXPHOS↓,
*toxicity↓, Normal cells remain unharmed
ROS↑, well known that this compound generates ROS
GSH↓,
eff↑, 3BP demonstrates synergistic activity with other compounds that reduce intracellular levels of GSH


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 25

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↓, 1,   GPx↓, 1,   GSH↓, 7,   H2O2↑, 1,   MDA↑, 1,   OXPHOS↓, 4,   mt-OXPHOS↓, 3,   ROS↑, 8,   Thiols↓, 1,   xCT↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↓, 1,   AIF↑, 1,   ATP↓, 12,   mitResp↓, 1,   MPT↑, 1,   mtDam↑, 3,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   ECAR↓, 1,   GAPDH↓, 4,   GlutaM↓, 1,   Glycolysis↓, 14,   HK2?, 1,   HK2↓, 13,   lactateProd↓, 1,   LDH↓, 3,   NADPH↓, 1,   PDH↓, 2,   PPP↑, 1,   TCA↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↑, 1,   Apoptosis↑, 4,   Bcl-2↓, 3,   Casp↑, 1,   Casp3↓, 1,   Casp3↑, 3,   Cyt‑c↑, 4,   Ferroptosis↓, 1,   Mcl-1↓, 2,   TumCD↑, 2,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 2,  

Autophagy & Lysosomes ⓘ

p‑Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   p62↓, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   PARP↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   FOXO3↑, 1,   HDAC↓, 1,   TumCG↓, 4,  

Migration ⓘ

MMP9↓, 1,   TGF-β↓, 1,   TumCA↑, 1,   TumCI↓, 1,   TumCP↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,  

Immune & Inflammatory Signaling ⓘ

NK cell↑, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 1,   ChemoSen↑, 2,   Dose↓, 1,   Dose↝, 6,   eff↓, 3,   eff↑, 13,   eff↝, 1,   RadioS↑, 2,   selectivity↑, 6,  

Clinical Biomarkers ⓘ

LDH↓, 3,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 1,   OS↑, 3,   QoL↑, 2,   Remission↑, 1,   toxicity↓, 6,   toxicity↑, 4,   toxicity↝, 4,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 84

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 1

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#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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