In THP-1-derived macrophages, AS-605240 treatment (10 μM, 24 h) reduced SR-A, CD36 and LPL mRNA relative to DMSO vehicle. TGX-221 and IC-87114 also reduced SR-A and CD36, while only AS-605240 significantly reduced LPL in this comparison. These transcript endpoints do not establish reduced LDL uptake by AS-605240 or an effect unique to PI3Kγ. [2]
Recombinant human PI3K isoform inhibition profile
Biochemical assay · Recombinant human PI3Kγ and human PI3Kα, PI3Kβ and PI3Kδ with p85α [1]
One isoform-profiling design supports preferential, rather than exclusive, inhibition of PI3Kγ. Absolute potency values are deferred because the primary table unit prefix is missing in the retained rendering.
Literature-Reported Treatment Conditions
- Exposure duration
- α/β/δ reactions stopped after 2 h; γ duration not established from the read assay paragraph.
- Method
- Cell-free lipid kinase assays with isoform-specific ATP, lipid and buffer conditions.
- Vehicle
- DMSO comparator
- Reported limits
- Absolute inhibitor concentrations, complete concentration range, n and uncertainty for the profile were not established from retrieved original material. Main Results/full Figure 1 caption were not retrieved.
Methods and source locations
Compound reported in the paper: AS-605240; Compound label in the paper: AS-605240
Qualitative inhibition profile of the paper-reported AS-605240; no salt conversion, PK, purity or Adooq lot claim.
Supplementary Table 3, AS-605240 row and comparator rows; Supplementary Methods p. 1, lipid kinase assays; Figure 1a,b
Relative inhibitory profile for human class I PI3K lipid kinase activity: Radiometric lipid kinase activity readout with scintillation proximity detection; inhibitor compared with DMSO. Table 3 supplies the comparative profile. — Supplementary Table 3, AS-605240 row; Supplementary Methods p. 1, in vitro lipid kinase assays
Comparative inhibitor effects on macrophage lipid-uptake-associated transcripts
Cell-based study · PMA-differentiated human THP-1 macrophages [2]
AS-605240 decreased SR-A, CD36 and LPL transcripts. Other inhibitors decreased SR-A and CD36 without a significant LPL decrease. AS-specific LDL uptake, protein response and viability were not verified; this design does not establish an exclusively PI3Kγ-mediated effect.
Literature-Reported Treatment Conditions
- Treatment concentration
- 10 μM AS-605240; TGX-221 and IC-87114 each tested separately at 10 μM
- Exposure duration
- 24 h inhibitor exposure
- Method
- THP-1 macrophages differentiated with 160 nM PMA for 24 h before the reported inhibitor comparison; mRNA measured by RT-qPCR.
- Vehicle
- DMSO vehicle control; vehicle percentage not established from read text
- Co-treatment
- No inhibitor combination in Figure 7; each inhibitor is a separate condition.
- Reported limits
- AS-specific viability validation and dose-response SI were not verified. SI retrieval returned HTML rather than PDF. Exact transcript fold changes were not tabulated in the read results and were not estimated from bars.
Methods and source locations
Compound reported in the paper: AS-605240; Compound label in the paper: AS-605240; TGX-221 and IC-87114 are separate comparators
Only the paper-reported AS-605240 cellular treatment and transcript response; no claim of independent analytical verification of the supplied product.
Results: More Isoform-Selective Inhibitors of the PI3K Pathway also Attenuate the Expression of SR-A, CD36 and LPL in Human Macrophages; Figure 7A–C and caption; Methods: Reagents, Cell Culture, Real-Time Quantitative PCR, Statistical Analysis
SR-A, CD36 and LPL mRNA normalized to RPL13A and DMSO vehicle: Comparative Ct RT-qPCR; one-way ANOVA with Games-Howell post hoc analysis. Significance symbols read in Figure 7; exact bar heights were not digitized. — Figure 7A–C and caption; Methods: Real-Time Quantitative PCR and Statistical Analysis
