Long Analysis Plan
LXR623 has been tested in two distinct disease models with different dose ranges and endpoints. In SPG3A patient-derived iPSC neurons, a single dose of 1 ΞΌM rescued synaptic gene expression, synapsin density, calcium activity, axonal swellings, and apoptosis versus DMSO control, with multiple biological replicates (n=3 per group for several assays) across two ATL1 mutant lines (P342S, M408T) plus isogenic corrected and wild-type controls .
In clear cell renal cell carcinoma (ccRCC), LXR623 was dose-mapped by IC50 viability assays: 569.3 nM in 786-O and 874.2 nM in ACHN cells, with selective sparing of non-malignant HK2 cells; RNA-seq at 0.1 ΞΌM for 48 h showed ABCA1/MYLIP upregulation and LDLR downregulation .
| Model | Endpoint | Assay | Dose | Replicates / n | Reported Outcome |
|---|---|---|---|---|---|
| SPG3A iPSC neurons (ATL1-P342S, M408T) | Synaptic rescue | Synapsin density, calcium imaging, Caspase 3/7, axonal swelling | 1 ΞΌM vs DMSO | n=3 per group (several assays); 2 patient lines + isogenic corrected + WT controls | Restored lipid/synaptic genes, synapsin clusters, calcium activity; fewer swellings; less apoptosis |
| SPG3A iPSC astrocytes | Cholesterol efflux | Cholesterol efflux assay | LXR623 (per study protocol) | Multiple biological replicates | Efflux deficits mitigated |
| ccRCC 786-O | Cell viability IC50 | CCK-8 | Dose-response | In vitro assay | IC50 = 569.3 nM |
| ccRCC ACHN | Cell viability IC50 | CCK-8 | Dose-response | In vitro assay | IC50 = 874.2 nM |
| ccRCC 786-O (transcriptome) | Cholesterol transport genes | RNA-seq | 0.1 ΞΌM, 48 h | RNA-seq experiment | ABCA1 β, MYLIP β, LDLR β |
| ccRCC 786-O / ACHN | Intracellular cholesterol | Cholesterol content assay | LXR623 treatment | Two cell lines | Cholesterol decreased; exogenous cholesterol partially rescued viability |
Limitations: The SPG3A study used a single reported dose (1 ΞΌM) without a full dose-response curve, and relies on two patient lines with in vitro-only validation . The ccRCC study mapped doses via IC50 in only two cell lines and one in vivo drug (SR9243) in immunodeficient mice, so LXR623 in vivo dose mapping is missing; lipid-rescue experiments suggest resistance via compensatory uptake . Confidence: moderateβvalues are as reported; missing full dose-response curves and replicate-level scatter for both studies.
Top Data Sources
ExportMCP
Analysis Wizard
DiscussionKnow what changed, what holds up, and what remains uncertain. Every Friday. No ads.
Explore by Goal
Ask a Follow-Up
Keep Exploring
Science Movie