Phospholipase Inhibitor

Malabaricone C is an orally active and noncompetitive sphingomyelin synthase (SMS) inhibitor with IC₅₀ values of 3 μM and 1.5 μM for SMS 1 and SMS 2, respectively. Malabaricone C reduces body weight gain, improves glucose tolerance, and decreases lipid accumulation in the liver, showing significant prevention of high fat diet-induced fatty liver in mice. Malabaricone C has anti-inflammatory effects, which is found in the fruits of Myristica cinnamomea King. Malabaricone C is promising for research of obesity and immunological disorders caused due to hyper-activation of T-cells.

Manumycin A is a polyketide antibiotic and an inhibitor of thioredoxin reductase 1 (TrxR-1). Manumycin A can inhibit the growth of breast cancer cells and exert its anti-tumor activity through LC3. Manumycin A can downregulate the release of pro-inflammatory cytokines in human monocytes stimulated by TNF α, and has potential anti-inflammatory activity. Manumycin A can inhibit the Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration resistant prostate cancer cells to suppress exosome biogenesis and secretion.

Tanshinone I is an inhibitor of type IIA human recombinant sPLA₂ (IC₅₀=11 μM) and rabbit recombinant cPLA₂ (IC₅₀=82 μM).

MAFP (Methyl Arachidonyl Fluorophosphonate) is an selective, active-site directed and irreversible inhibitor of cPLA2 and iPLA2. MAFP is also a potent irreversible inhibitor of anandamide amidase.

DPTIP is a potent brain penetrant neutral sphingomyelinase 2 (N-SMase 2) inhibitor (exosome inhibitor), with an IC₅₀ of 30 nM.

Bromoenol lactone ((6E)-Bromoenol lactone) is a suicide-based irreversible, selective, potent inhibitor of calcium-independent phospholipase A₂ (iPLA₂β) with an IC₅₀ value of approximately 7 μM, which inhibits antigen-stimulated mast cell exocytosis without blocking Ca²⁺ influx.

LEI-401 is a first-in-class, selective, and CNS-active NAPE-PLD (N-acylphosphatidylethanolamine phospholipase D) inhibitor, with an IC₅₀ of 27 nM. LEI-401 modulates emotional behavior in mice.

Magnesium sulfate is a calcium antagonist and a potent L-type calcium channel inhibitor, as well as a tocolytic. Magnesium sulfate has anti-inflammatory, anticonvulsant, vasodilatory, and neuroprotective effects. Magnesium sulfate can be used in the research of diseases such as preeclampsia/eclampsia.

CCT129957 is an indole derivative and a potent phospholipase C-γ (PLC-γ) inhibitor with an IC₅₀ of ~3 μM and a GC₅₀ of 15 μM. CCT129957 inhibits Ca²⁺ release in squamous carcinoma cells at ~15 μM.

SMS2-IN-1 is a potent and highly selective sphingomyelin synthase 2 (SMS2) inhibitor with an IC₅₀ of 6.5 nM and a K_d of 37 nM. SMS2-IN-1 shows 150-fold selectivity for SMS2 over SMS1 (IC₅₀ of 1000 nM).

Vinaxanthone (SM-345431) is a potent and selective semaphorin3A, phospholipase C (PLC) and FabI inhibitor, with IC₅₀s of 0.1-0.2 μM and 0.9 mM for semaphorin3A and FabI. Vinaxanthone inhibits the substrate (t-o-NAC thioester) and the cofactor (NADPH) with K_is of 3.1 μM and 1.0 μM, respectively. Vinaxanthone can be used to handle infections caused by multidrug-resistant pathogens.

Tris(2,4-di-tert-butylphenyl)phosphate is an active compound from the leaves of Vitex negundo L. shows anti-inflammatory activity with evidence of inhibition for secretory Phospholipase A₂ (sPLA₂) through molecular docking.

1-Naphthaleneacetic acid (1-Naphthylacetic acid), a auxin, can promote plant growth. 1-Naphthaleneacetic acid is also an inhibitor of PLA₂, with an IC₅₀ of 13.16 μM.

BAPTA tetrapotassium is a selective and cell-impermeant chelator for calcium. BAPTA has high selectivity against magnesium and calcium. BAPTA tetrapotassium can also inhibit phospholipase C activity independently of their role as Ca²⁺ chelators.

DS55980254 is the orally active inhibitor for phosphatidylserine synthase 1 (PTDSS1) that blocks the synthesis of intracellular phosphatidylserine. PTDSS1 deficiency affects the balance of cell membrane phospholipid components, and activates B cell receptor (BCR) signaling pathway.

Cambinol is a SIRT1 and SIRT2 inhibitor with IC₅₀ values of 56 μM and 59 μM, respectively. Cambinol is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor).

BAPTA tetrasodium is a selective and cell-impermeant chelator for calcium. BAPTA tetrasodium has high selectivity against magnesium and calcium. BAPTA can also inhibit phospholipase C activity independently of their role as Ca²⁺ chelators.

VU0359595 (CID-53361951; ML-270) is a potent and selective pharmacological phospholipase D1 (PLD1) inhibitor with an IC₅₀ of 3.7 nM. VU0359595 is >1700-fold selective for PLD1 over PLD2 (IC₅₀ of 6.4 μM). VU0359595 can be used for the research of cancer, diabetes, neurodegenerative and inflammatory diseases.

SMS1-IN-1, compound SAPA 1j, is a novel and the most potent sphingomyelin synthase 1 (SMS1) inhibitor with an IC₅₀ value of 2.1 μM. SMS1-IN-1 has the potential for the treatment of atherosclerosis.

MJ-33 lithium salt is a competitive phospholipase A₂ (PLA₂) inhibitor with an IC₅₀ of 0.3 μM. MJ-33 lithium salt inhibits NOX2 activation and reduces ROS production by blocking the PLA₂ activity of Prdx6. MJ-33 lithium salt effectively inhibits the activity of acidic PLA₂ (pH 4.0) and reduces the degradation of alveolar surfactant phosphatidylcholine (PC), but exerts no effect on alkaline PLA₂ (pH 8.5). MJ-33 lithium salt significantly alleviates lung oxidative injury induced by ischemia-reperfusion (I/R). MJ-33 lithium salt significantly inhibits the invasion, migration and adhesion abilities of prostate cancer cells by suppressing the MAPK, AKT, NF-κB and AP-1 signaling pathways. MJ-33 lithium salt can be used for the research of ROS-related diseases and prostate cancer.