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Fig. 1 · Structure
Cat. No.
A10548
CAS No.
172732-68-2
Formula
C21H20N2O5
Mol. Weight
380.4

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Varespladib (LY315920)

Cat. No. A10548 CAS 172732-68-2

HnsPLA inhibitor

LY315920 (Varespladib) is an inhibitor of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2).

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Publications for Varespladib

2 publications citing this product

  1. Yap WH, .et al. , Mol Cell Biochem, 2018, Oct;447(1-2):93-101 PMID: 29374817
  2. Yamato Okita, .et al. , Infect Immun, 2016, Feb; 84(2): 573-579 PMID: 26644377
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Biological Activity

Bioactivity / Mechanism

LY315920 (varespladib) inhibits secreted phospholipase A2 isoforms. In a recombinant-enzyme fluorometric panel, the matching free-acid structure (compound B) gave IC50 values of 0.125 ± 0.02 μM for human group IIA, 0.05 ± 0.02 μM for group IIE and 0.075 ± 0.01 μM for group X. Human group IB and V were less sensitive in that assay. The table reports duplicate or triplicate analyses but does not define the ± term. [1]

Apparent potency depends on the lipid substrate. In a recombinant human group V sPLA2 assay, the reported representative IC50 values were 0.104/0.131 μM with PAPC and 18/22 μM with PAPG, using lysophospholipid/free-arachidonic-acid LC–MS readouts, respectively. These assay endpoints should be interpreted with their substrate conditions. [2]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
hnsPLA2 7 nM

In Vitro Studies

In serum-deprived MDA-MB-231 breast cancer cells, 50 μM varespladib prevented the increase in EdU incorporation elicited by 10 nM recombinant human group X sPLA2 during a 24-hour treatment. The experiment included inhibitor-only and enzyme-only controls. This model-specific result supports a role for sPLA2 catalytic activity in the proliferative response. [3]

Recombinant human and mouse sPLA2 isoform inhibition panel

Biochemical assay · Recombinant human and mouse groups IB, IIA, IIE, V and X secreted phospholipase A2 [1]

Compound B inhibited multiple sPLA2 isoforms in a pyrene-phosphatidylglycerol vesicle assay. Human group IIE and X were more sensitive than group IB or V under these conditions. This is an assay-specific isoform profile, not a universal potency constant.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
human group ib sPLA2 catalytic activityIC50 0.75 ± 0.15 μM[1]
mouse group ib sPLA2 catalytic activityIC50 0.14 ± 0.075 μM[1]
human group iia sPLA2 catalytic activityIC50 0.125 ± 0.02 μM[1]
mouse group iia sPLA2 catalytic activityIC50 0.07 ± 0.02 μM[1]
human group iie sPLA2 catalytic activityIC50 0.05 ± 0.02 μM[1]
mouse group iie sPLA2 catalytic activityIC50 0.075 ± 0.02 μM[1]
human group v sPLA2 catalytic activityIC50 0.50 ± 0.05 μM[1]
mouse group v sPLA2 catalytic activityIC50 0.75 ± 0.10 μM[1]
human group x sPLA2 catalytic activityIC50 0.075 ± 0.01 μM[1]
mouse group x sPLA2 catalytic activityIC50 0.075 ± 0.01 μM[1]

Literature-Reported Treatment Conditions

Treatment concentration
Concentration-response assay; tested concentration range not given in the acquired main text.
Method
Fluorometric assay using unilamellar vesicles of 1-hexadecanoyl-2-(10-pyrenedecanoyl)-sn-glycero-3-phosphoglycerol; released pyrene fatty acid binds albumin and gives monomer emission.
Reported limits
SI assay procedures were not retrieved. Main text does not specify inhibitor vehicle, incubation duration or buffer composition. Table footnote gives duplicate or triplicate analyses without defining the meaning of ±.
Methods and source locations

Compound reported in the paper: LY315920 (varespladib); Compound label in the paper: Compound B

Molecular-structure applicability only; no Adooq material or lot was tested.

Figure 3B; main assay/results paragraphs immediately before Table 1; Table 1 compound B column and footnote a

human group ib sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, human group ib row; footnote a

mouse group ib sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, mouse group ib row; footnote a

human group iia sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, human group iia row; footnote a

mouse group iia sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, mouse group iia row; footnote a

human group iie sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, human group iie row; footnote a

mouse group iie sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, mouse group iie row; footnote a

human group v sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, human group v row; footnote a

mouse group v sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, mouse group v row; footnote a

human group x sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, human group x row; footnote a

mouse group x sPLA2 catalytic activity: Pyrene-phosphatidylglycerol fluorometric assay; duplicate or triplicate analyses; ± definition not specified in main Table 1. — Table 1, compound B, mouse group x row; footnote a

Substrate-dependent inhibition of recombinant human group V sPLA2

Biochemical assay · Recombinant human group V secreted PLA2 in PAPC or PAPG mixed micelles [2]

LY315920 inhibited group V sPLA2, but changing the substrate from PAPC to PAPG markedly reduced apparent potency. Representative Results-text IC50 values were 0.104 and 0.131 μM for PAPC versus 18 and 22 μM for PAPG, using positive- and negative-ion lipidomics readouts, respectively. These are fitted enzyme-assay endpoints, not cell treatment concentrations.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Human group V sPLA2 inhibition with PAPC substrate; 16:0 LPC readoutIC50 0.104 μM (representative curve; Results text)[2]
Human group V sPLA2 inhibition with PAPC substrate; 16:0 LPC readoutXI(50) 0.00015 ± 0.00001 (mole fraction; figure-fit ± term)[2]
Human group V sPLA2 inhibition with PAPC substrate; free arachidonic acid readoutIC50 0.131 μM (representative curve; Results text)[2]
Human group V sPLA2 inhibition with PAPC substrate; free arachidonic acid readoutXI(50) 0.00018 ± 0.00002 (mole fraction; figure-fit ± term)[2]
Human group V sPLA2 inhibition with PAPG substrate; 16:0 LPG readoutIC50 18 μM (representative curve; Results text)[2]
Human group V sPLA2 inhibition with PAPG substrate; 16:0 LPG readoutXI(50) 0.026 ± 0.002 (mole fraction; figure-fit ± term)[2]
Human group V sPLA2 inhibition with PAPG substrate; free arachidonic acid readoutIC50 22 μM (representative curve; Results text)[2]
Human group V sPLA2 inhibition with PAPG substrate; free arachidonic acid readoutXI(50) 0.032 ± 0.002 (mole fraction; figure-fit ± term)[2]

Literature-Reported Treatment Conditions

Treatment concentration
Dose-response series; inhibitor stock 5 mM in DMSO. Stock concentration is not an assay treatment dose.
Exposure duration
30 min reaction at 40 °C
Method
LC–MS quantification of lysophospholipid and free arachidonic acid. Mixed micelles contained 100 μM phospholipid and 400 μM C12E8; group V assay buffer: 50 mM Tris-HCl, pH 8.0, and 5 mM CaCl2. No-enzyme blanks assessed nonenzymatic hydrolysis; internal standards supported normalization.
Vehicle
DMSO stock; final DMSO fraction not specified in the read method.
Reported limits
Final inhibitor vehicle fraction and enzyme amount are not specified in the read method. Figure-fit ± terms are not explicitly labeled SD or SEM; Table 2 caption says standard error but its dispersion row is labeled STDEV. No aggregate ± estimate is adopted.
Methods and source locations

Compound reported in the paper: LY315920 (varespladib); Compound label in the paper: Ly315920

Reported LY315920 material, without assuming Adooq supply or lot equivalence.

Results: Assay Development and Validation; Substrate Affinity Affects Competitive Inhibitors; Figures 4A-B and 5A-B; Experimental: Lipidomics PLA2 Assay and Reagents

Human group V sPLA2 inhibition with PAPC substrate; 16:0 LPC readout: LC–MS positive ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 4A annotation/caption; corresponding Results paragraph in Assay Development and Validation

Human group V sPLA2 inhibition with PAPC substrate; 16:0 LPC readout: LC–MS positive ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 4A annotation/caption; corresponding Results paragraph in Assay Development and Validation

Human group V sPLA2 inhibition with PAPC substrate; free arachidonic acid readout: LC–MS negative ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 4B annotation/caption; corresponding Results paragraph in Assay Development and Validation

Human group V sPLA2 inhibition with PAPC substrate; free arachidonic acid readout: LC–MS negative ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 4B annotation/caption; corresponding Results paragraph in Assay Development and Validation

Human group V sPLA2 inhibition with PAPG substrate; 16:0 LPG readout: LC–MS positive ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 5A annotation/caption; corresponding Results paragraph in Substrate Affinity Affects Competitive Inhibitors

Human group V sPLA2 inhibition with PAPG substrate; 16:0 LPG readout: LC–MS positive ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 5A annotation/caption; corresponding Results paragraph in Substrate Affinity Affects Competitive Inhibitors

Human group V sPLA2 inhibition with PAPG substrate; free arachidonic acid readout: LC–MS negative ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 5B annotation/caption; corresponding Results paragraph in Substrate Affinity Affects Competitive Inhibitors

Human group V sPLA2 inhibition with PAPG substrate; free arachidonic acid readout: LC–MS negative ion mode; XI(50) is inhibitor mole fraction in total substrate interface at 50% inhibition; figure-fit ± meaning not explicitly defined. — Figure 5B annotation/caption; corresponding Results paragraph in Substrate Affinity Affects Competitive Inhibitors

Blockade of hGX-stimulated proliferation in serum-deprived MDA-MB-231 cells

Cell-based study · Human MDA-MB-231 breast cancer cells, serum-deprived for 48 h before 24 h treatment [3]

At 50 μM, varespladib prevented the increase in EdU incorporation induced by 10 nM recombinant human group X sPLA2. Figure 1A includes untreated, hGX-only, varespladib-only and combination groups. The result supports enzyme-dependent mitogenic signaling in this model; it does not establish broad anticancer activity or cell killing.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
EdU-positive cells / S-phase proliferation response to recombinant hGXQualitative controlled response hGX-stimulated EdU incorporation was abolished by 50 μM varespladib; exact bar percentages were not extracted.[3]

Literature-Reported Treatment Conditions

Treatment concentration
50 μM varespladib; 10 nM recombinant hGX sPLA2
Exposure duration
24 h treatment after 48 h serum deprivation
Method
Serum-free medium containing 0.1% fatty-acid-free BSA. Methods describe preincubating varespladib with enzyme for 15 min before adding the mixture to cells. EdU/7-AAD flow cytometry measured proliferation.
Co-treatment
hGX enzyme challenge; untreated, hGX-only and varespladib-only controls included.
Reported limits
Inhibitor solvent/final vehicle concentration not specified in the read methods. Figure caption reports at least two experiments in duplicate without an exact experiment count.
Methods and source locations

Compound reported in the paper: LY315920 (varespladib); Compound label in the paper: Var

Applies to reported LY315920 treatment at compound-name level; no lot validation or salt conversion implied.

Figure 1A; first Results subsection; Materials, Cell lines and culture conditions, Cell proliferation assay, Statistical analysis

EdU-positive cells / S-phase proliferation response to recombinant hGX: EdU incorporation with 7-AAD flow cytometry; EdU present for last 6 h. Caption: means ± SD of at least two experiments in duplicate; one-way ANOVA with Bonferroni adjustment. hGX-only versus untreated control marked *** (P < 0.001); a separate combination-versus-hGX P value is not given. — Figure 1A image/caption; first Results subsection; Materials and methods: Cell proliferation assay

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 172732-68-2
Applications HnsPLA inhibitor
Formula C21H20N2O5
Molecular Weight 380.4
Synonyms S-5920; LY315920
SMILES
CCC1=C(C2=C(N1CC3=CC=CC=C3)C=CC=C2OCC(=O)O)C(=O)C(=O)N

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 73 mg/mL (191.9 mM)
Water Insoluble
Ethanol Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration
28 mg/mL
Vehicle
30% PEG400+0.5% Tween80+5% propylene glycol

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Brian P. Smart, Rob C. Oslund, Laura A. Walsh, et al. The First Potent Inhibitor of Mammalian Group X Secreted Phospholipase A2: Elucidation of Sites for Enhanced Binding Journal of Medicinal Chemistry (2006). PMID: 16686528 DOI: 10.1021/jm060136t Source material
  2. [2] Varnavas D. Mouchlis, Aaron Armando, Edward A. Dennis. Substrate-Specific Inhibition Constants for Phospholipase A2 Acting on Unique Phospholipid Substrates in Mixed Micelles and Membranes Using Lipidomics Journal of Medicinal Chemistry (2019). PMID: 30615445 DOI: 10.1021/acs.jmedchem.8b01568 Source material
  3. [3] Anja Pucer, Vesna Brglez, Christine Payré, et al. Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival Molecular Cancer (2013). PMID: 24070020 DOI: 10.1186/1476-4598-12-111 Source material

Publications

2 publications citing this product

  1. Yap WH, .et al. , Mol Cell Biochem, 2018, Oct;447(1-2):93-101 PMID: 29374817
  2. Yamato Okita, .et al. , Infect Immun, 2016, Feb; 84(2): 573-579 PMID: 26644377

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