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Floatptosis: Lysosomal Fusion-Associated Termination Of Cell Death

Cell Programmed Death Cell Death & Disease Intercellular Communication & Diseases Inflammation Initiation Complex

Floatptosis is a newly reported cytoplasmic vacuolization cell death pathway defined as "Fused LysosOme-Associated Termination" in macrophages infected by a Bergeyella cardium variant. Its current research base is narrow but mechanistically important because it links bacterial infection, macrophage death, lysosomal fusion, and immune evasion. The discovery builds on a broader cell-death literature that moved from morphology-based descriptions toward molecular definitions and on earlier work showing that cytoplasmic vacuolization can accompany either cell death or survival depending on context[1][2][3].

Mechanistically, BCV induces robust cytoplasmic vacuolization cell death and minor apoptosis-like cell death in macrophages. The vacuoles induced by BCV colocalize with Rab7 and LAMP1, indicating late endosomal and lysosomal features. BCV-derived outer membrane vesicles and barrel-like membrane proteins, including lipocalin, β-barrel, and PorV, induce cytoplasmic vacuolization. SLC9A9 promotes vacuole fusion during BCV-, OMV-, and barrel-like protein-triggered floatptosis, while amiloride inhibits cytoplasmic vacuolization, LDH release, caspase-3 activation, and GSDME cleavage. The pathway differs from apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-dependent death, and classical methuosis because z-VAD, necroptosis inhibitors, ferroptosis inhibition, autophagy modulation, mTORC1 modulation, and NF-κB inhibition did not block BCV-triggered vacuolization[1][2][4][5].

Disease relevance currently centers on infectious disease and host defense. Bergeyella cardium is described as an infective endocarditis causative pathogen, and BCV shows stronger intracellular propagation and in vivo pathogenicity than the original strain. SLC9A9 deficiency or amiloride administration increased host defense against BCV infection, and amiloride treatment reduced lung bacterial burden in infected mice. These findings position SLC9A9, endosomal ion transport, bacterial OMVs, and pathogen-derived β-barrel proteins as early drug-discovery entry points for modulating macrophage vacuolization cell death during bacterial infection[1].

The main limitation is that floatptosis is presently supported by one primary published study, so the field still needs independent validation, standardized biomarkers, additional pathogens, human-cell confirmation, and clearer boundaries from lysosome-dependent cell death and methuosis. Future research should define whether floatptosis occurs beyond macrophages, whether SLC9A9 is a universal executor or BCV-specific cofactor, and whether pharmacological blockade can improve infection outcomes without impairing protective immune-cell functions. The near-term prospect is cautious but concrete: floatptosis offers a new framework for studying pathogen-controlled lysosomal fusion, vacuolization-associated cell death, and anti-infective host-directed therapy[1][2][3][5].

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Cat. No. Product Name Information Application Publication
HY-16658B Z-VAD-FMK
Z-VAD-FMK is a pan-caspase inhibitor and also an ICE-like protease inhibitor, which inhibits apoptosis by preventing the processing of CPP32 to its active form. Z-VAD-FMK sensitivity varies primarily due to differential expression of receptor-interacting protein 1 (RIP1). Z-VAD-FMK limits the cryopreservation-induced apoptosis by reducing caspase-3 activity of in vitro produced bovine embryos. Z-VAD-FMK is immunosuppressive in vitro and inhibits T cell proliferation without blocking the processing of caspase-8 and caspase-3. Z-VAD-FMK leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. Z-VAD-FMK is due to oxidative stress via the depletion of GSH. Z-VAD-FMK can be used for the study of acute pancreatitis.
Caspase   Apoptosis   RIP kinase   Glutathione Peroxidase   Reactive Oxygen Species (ROS)  
Cancer   Digestive System Disease   Pancreatitis  
853
HY-15760 Necrostatin-1
Necrostatin-1 (Nec-1) is a potent and cross the blood-brain barrier necroptosis inhibitor with an EC50 of 490 nM in Jurkat cells. Necrostatin-1 inhibits RIP1 kinase (EC50=182 nM). Necrostatin-1 is also an IDO inhibitor.
RIP kinase   Autophagy   Indoleamine 2,3-Dioxygenase (IDO)   Ferroptosis   Necroptosis  
Cancer   Neurological, Eye or Ear Disease   Digestive System Disease   Digestive System Inflammation  
576
HY-16658 Z-VAD(OMe)-FMK
Z-VAD(OMe)-FMK (Z-Val-Ala-Asp(OMe)-FMK) is a cell-permeable and irreversible pan-caspase inhibitor. Z-VAD(OMe)-FMK is an ubiquitin carboxy-terminal hydrolase L1 (UCHL1) inhibitor. Z-VAD(OMe)-FMK irreversibly modifies UCHL1 by targeting the active site of UCHL1.
Caspase  
Cancer  
211
HY-13205 Belnacasan
Belnacasan (VX-765) is an orally bioactive proagent of VRT-043198, which is a potent and selective inhibitor of IL-converting enzyme (ICE)/caspase-1 with Kis of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. Belnacasan (VX-765) inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC50 of ~0.7 μM.
Caspase  
Inflammation or Immune System Disease   Depression   Pain  
181
HY-100573 Necrosulfonamide
Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.
Mixed Lineage Kinase   Necroptosis   Pyroptosis   Caspase   NOD-like Receptor (NLR)   Keap1-Nrf2   TNF Receptor   Interleukin Related   NO Synthase   Heme Oxygenase (HO)  
Digestive System Disease   Prostate Cancer   Leukemia/Lymphoma/Myeloma   Depression   Digestive System Inflammation   Cardiovascular Disease   Parkinson's Disease   Obesity   Lung Fibrosis   Rheumatoid Arthritis  
147
HY-12466 Z-DEVD-FMK
Z-DEVD-FMK is a specific and irreversible caspase-3 inhibitor with an IC50 of 18 μM.
Caspase  
Cancer   Neurodegenerative Disease  
139
HY-12305 Q-VD-OPh
Q-VD-OPh is an irreversible pan-caspase inhibitor with potent antiapoptotic properties; inhibits caspase 7 with an IC50 of 48 nM and 25-400 nM for other caspases including caspase 1, 3, 8, 9, 10, and 12. Q-VD-OPh can inhibits HIV infection. Q-VD-OPh is able to cross the blood-brain barrier.
Caspase   HIV  
Leukemia/Lymphoma/Myeloma   Viral Infection   Alzheimer's Disease  
117
HY-101872A GSK-872 hydrochloride
GSK-872 hydrochloride is a RIPK3 inhibitor, which binds RIP3 kinase domain with an IC50 of 1.8 nM, and inhibits kinase activity with an IC50 of 1.3 nM. GSK-872 hydrochloride decreases the RIPK3-mediated necroptosis and subsequent cytoplasmic translocation and expression of HMGB1, as well as ameliorates brain edema and neurological deficits in early brain injury.
RIP kinase  
Inflammation or Immune System Disease  
114
HY-101872 GSK-872
GSK-872 is a RIPK3 inhibitor, which binds RIP3 kinase domain with an IC50 of 1.8 nM, and inhibits kinase activity with an IC50 of 1.3 nM. GSK-872 decreases the RIPK3-mediated necroptosis and subsequent cytoplasmic translocation and expression of HMGB1, as well as ameliorates brain edema and neurological deficits in early brain injury.
RIP kinase  
Inflammation or Immune System Disease  
114
HY-19696 Tauroursodeoxycholate
Tauroursodeoxycholate (Tauroursodeoxycholic acid) is an orally active endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.
ERK   Caspase   Endogenous Metabolite   Apoptosis  
Colorectal Cancer   Prostate Cancer   Liver Cancer   Viral Infection   Neurodegenerative Disease   Pain   Digestive System Inflammation   Glucose Metabolism   Obesity  
111
HY-13755 Sulforaphane
Sulforaphane is an orally active inducer of the Keap1/Nrf2/ARE pathway. Sulforaphane promotes the transcription of tumor-suppressing proteins and effectively inhibits the activity of HDACs. Through the activation of the Keap1/Nrf2/ARE pathway and further induction of HO-1 expression, Sulforaphane protects the heart. Sulforaphane suppresses high glucose-induced pancreatic cancer through AMPK-dependent signal transmission. Sulforaphane exhibits both anticancer and anti-inflammatory properties.
HDAC   Keap1-Nrf2   Apoptosis   Bcl-2 Family   Caspase   Reactive Oxygen Species (ROS)  
Inflammation or Immune System Disease  
79
HY-B1081A Oxidopamine hydrobromide
Oxidopamine (6-OHDA) hydrobromide is an antagonist of the neurotransmitter dopamine. Oxidopamine hydrobromide is a widely used neurotoxin and selectively destroys dopaminergic neurons. Oxidopamine hydrobromide promotes COX-2 activation, leading to PGE2 synthesis and pro-inflammatory cytokine IL-1β secretion. Oxidopamine hydrobromide can be used for the research of Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD), and Lesch-Nyhan syndrome.
Dopamine Receptor   Autophagy   Mitophagy   COX   PGE synthase   Interleukin Related   p38 MAPK   Apoptosis   Caspase  
Breast Cancer   Parkinson's Disease  
50
HY-14622A Necrostatin 2 racemate
Necrostatin 2 racemate (Nec-1S), the Necrostatin-1 (HY-15760) stable, is a potent and specific RIPK1 inhibitor lacking the IDO-targeting effect.
RIP kinase  
Cancer  
40
HY-14654 Aspirin
Aspirin (Acetylsalicylic acid) is an orally active, potent and irreversible inhibitor of cyclooxygenase COX-1 and COX-2, with IC50 values of 5 and 210 μg/mL, respectively. Aspirin induces apoptosis. Aspirin inhibits the activation of NF-κB. Aspirin also inhibits platelet prostaglandin synthetase, and can prevent coronary artery and cerebrovascular thrombosis.
Environmental Pollutants   Apoptosis   Virus Protease   NF-κB   Mitophagy   p38 MAPK   Autophagy   COX   Caspase  
Breast Cancer   Colorectal Cancer   Prostate Cancer   Liver Cancer   Leukemia/Lymphoma/Myeloma   Pancreatic Cancer   Ovarian Cancer   Viral Infection   Neurodegenerative Disease   Depression   Pain   Digestive System Inflammation   Cardiovascular Disease   Non-Small Cell Lung Cancer   SARS-CoV-2 Infection   Obesity   Rheumatoid Arthritis  
38
HY-15594A Phen-DC3 Trifluoromethanesulfonate
Phen-DC3 Trifluoromethanesulfonate is a bisquinolinium G-quadruplex (G4) ligand. Phen-DC3 Trifluoromethanesulfonate selectively binds to and stabilizes the hybrid quadruplex-duplex hybrid (QDH) derived from the PIM1 promoter. Phen-DC3 Trifluoromethanesulfonate also binds to the c-myc promoter Pu24T G4 via extensive π-stacking, and induces polymerase stalling at α-synuclein DNA and RNA G4 sequences. Phen-DC3 Trifluoromethanesulfonate downregulates LPS (HY-D1056)-induced TNFRSF21, RIPK3 and p-MLKL in VECs, and ameliorates CLP-induced pulmonary vascular leakage in septic rats. Phen-DC3 Trifluoromethanesulfonate can be used in studies related to neurodegenerative diseases and sepsis-associated vascular injury.
G-quadruplex   α-synuclein   RIP kinase  
Neurodegenerative Disease   Sepsis  
13
HY-100339 GSK583
GSK583 is a highly potent, orally active and selective inhibitor of RIP2 Kinase, with IC50 of 5 nM. GSK583 inhibits both TNF-α and IL-6 production with an IC50 value of 200 nM.
RIP kinase  
Metabolic or Endocrine Disease   Prostate Cancer   Depression   Pain  
9
HY-144828 RIP1/RIP3/MLKL activator 1
RIP1/RIP3/MLKL activator 1 (Compound 6i) is a potent anti-glioma agent. RIP1/RIP3/MLKL activator 1 induces necroptosis through RIP1/RIP3/MLKL pathway. RIP1/RIP3/MLKL activator 1 exerts acceptable BBB permeability.
RIP kinase   Mixed Lineage Kinase   Necroptosis  
Cancer  
7
HY-B0339 Primidone
Primidone is the orally active inhibitor for TRPM3 (IC50 = 0.6 μM), RIP kinase and voltage-gated sodium channel, and the antagonist for GABA receptor. Primidone can be used as the analgesic and anticonvulsant agent.
TRP Channel   RIP kinase   Sodium Channel   GABA Receptor   Necroptosis  
Digestive System Disease   Pain   Digestive System Inflammation   SARS-CoV-2 Infection   Alzheimer's Disease   Parkinson's Disease  
2
HY-157442 GLPG3312
GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC50 values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.
Salt-inducible Kinase (SIK)   Discoidin Domain Receptor   RIP kinase   LIM Kinase (LIMK)   MAP3K   Bcr-Abl   Src   TGF-β Receptor  
Inflammation or Immune System Disease  
1

Targets/Pathways

Keywords

floatptosis, lysosomal fusion, cytoplasmic vacuolization, macrophage cell death, Bergeyella cardium, SLC9A9, amiloride, bacterial OMVs