Orlistat / PD-L1 Cancer Research Results

OLST, Orlistat: Click to Expand ⟱
Features:

Orlistat (tetrahydrolipstatin; anti-obesity drug; OTC 60 mg, Rx 120 mg). A potent, minimally absorbed gastrointestinal lipase inhibitor that reduces dietary fat absorption (~30% at 120 mg TID).

Primary mechanisms (conceptual rank):
1) Irreversible inhibition of gastric + pancreatic lipases (↓ triglyceride hydrolysis)
2) ↓ Chylomicron formation → ↓ systemic lipid flux
3) Secondary metabolic shifts (weight loss–mediated insulin sensitivity changes)

Bioavailability / PK relevance: Very low systemic absorption (<1%); primary action is intraluminal in gut. Most systemic mechanistic cancer data derive from higher in-vitro concentrations or off-target effects (e.g., FASN inhibition).

In-vitro vs oral exposure: Many anti-cancer studies use concentrations likely exceeding achievable plasma levels from standard dosing (qualifier: high concentration only for direct tumor cytotoxicity).

Clinical evidence status: Approved for obesity; cancer evidence largely preclinical/observational; no robust oncology RCT indication.

Inhibits lipase and is used to facilitate weight loss.

Orlistat — Cancer vs Normal Cell Pathway Map

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Fatty Acid Synthase (FASN) ↓ (high concentration only) ↔ (low FASN dependence) R/G Lipid synthesis blockade; apoptosis Well-known off-target in vitro; many tumors overexpress FASN. Clinical relevance limited by low systemic exposure.
2 Lipid availability / metabolic flux ↓ (indirect) ↓ (systemic) G Reduced lipid supply Weight-loss–mediated effect; may indirectly reduce pro-tumor metabolic signaling (insulin/IGF axis).
3 PI3K/AKT/mTOR ↓ (model-dependent) ↔ / ↓ (metabolic improvement) R/G Reduced anabolic signaling Often secondary to lipid stress or metabolic shifts; not primary gut mechanism.
4 Apoptosis (caspase activation) ↑ (high concentration only) ↔ R/G Programmed cell death Observed in cancer lines at supra-physiologic levels; translation uncertain.
5 ROS / lipid peroxidation stress ↑ (lipid stress–related; model-dependent) ↔ P/R Metabolic oxidative stress Linked to FASN inhibition; not central to approved mechanism.
6 NRF2 axis ↔ (insufficient evidence) ↔ R/G Not a dominant axis No consistent evidence of primary NRF2 modulation at therapeutic exposure.
7 Ferroptosis (lipid metabolism link) ↑ (theoretical / model-dependent) ↔ R/G Lipid vulnerability shift FASN inhibition could alter lipid composition; ferroptosis relevance remains investigational.
8 HIF-1α / Warburg coupling ↓ (indirect; metabolic improvement) ↔ G Reduced pro-growth metabolic signaling Likely secondary to weight loss and insulin reduction rather than direct tumor action.
9 Ca²⁺ signaling ↔ ↔ P/R No primary role Not a recognized mechanistic axis for orlistat.
10 Clinical Translation Constraint ↓ (constraint) ↓ (constraint) — Minimal systemic exposure Low absorption limits direct anti-tumor applicability; GI side effects and fat-soluble vitamin malabsorption noted.

TSF legend: P: 0–30 min; R: 30 min–3 hr; G: >3 hr
PD-L1, Programmed Death-Ligand 1: Click to Expand ⟱
Source:
Type:
PD-L1 is a protein that plays a crucial role in the regulation of the immune system. PD-L1 helps to prevent the immune system from attacking healthy cells by binding to its receptor, PD-1, on immune cells. However, some cancer cells can exploit this mechanism by expressing high levels of PD-L1, which can help them evade immune detection.
PD-L1 has become a key target for cancer immunotherapy, particularly in the development of checkpoint inhibitors.

PD-1: Upregulated on tumor-infiltrating lymphocytes (TILs), reflecting chronic antigen exposure and an “exhausted” T cell phenotype.
PD-L1 and PD-L2: Frequently overexpressed by many tumor types (e.g., non–small cell lung cancer, melanoma, renal cell carcinoma, head and neck cancers.
Scientific Papers found: Click to Expand⟱
1045- OLST,    Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line
- in-vitro, AML, Jurkat
FASN↓, TumCG↓, PD-L1↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis ⓘ

FASN↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 1,  

Immune & Inflammatory Signaling ⓘ

PD-L1↓, 1,  

Clinical Biomarkers ⓘ

PD-L1↓, 1,  
Total Targets: 4

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: PD-L1, Programmed Death-Ligand 1
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:14  Target#:243  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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