Orlistat

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Cat Number

API96829582

CAS Number

96829-58-2

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Product Detail Description Scientific Support Advanced Innovations Customer Q&A

CAS Number

96829-58-2

EINECS

639-755-1

Storage

Store at -20℃

Synonyms

(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate; N-Formyl-L-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester

Molecular Formula

C29H53NO5

Molecular Weight

495.73

Smiles

CCCCCCCCCCC[C@@H](C[C@H]1[C@@H](C(=O)O1)CCCCCC)OC(=O)[C@H](CC(C)C)NC=O

Appearance

Solid

Standard

USP In-house

General Description

Orlistat is a carboxylic ester formed by the condensation of N-formyl-L-leucine’s carboxy group with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. This pancreatic lipase inhibitor functions as an anti-obesity medication by blocking fat absorption in the digestive system.

Mechanism of Action

Orlistat binds covalently to the active site of pancreatic lipase and forms a stable complex. This results in a conformational change in the enzyme that results in the opening of a lid-like structure on the lipase, thus exposing the catalytic active site. The mechanism of action then leads to acylation of a hydroxyl group on serine residue present on the active site of the enzyme rendering it inactive as lipase. The inactivated lipase is no longer able to hydrolyse fats into fatty acids and monoglycerides, which pass through with faeces.

Application

Orlistat, primarily used as a potent, long-acting, non-systemically absorbed gastrointestinal lipase inhibitor, is widely employed for the long-term treatment of obesity or overweight in adults. Beyond its core functions of weight loss and weight management, recent biomedical research has revealed its potential in the anti-tumor field, discovering that it can induce apoptosis in various cancer cells by inhibiting fatty acid synthase (FASN) and regulating multiple cell signaling pathways (such as NF-κB, AKT/mTOR), providing new directions for adjuvant therapy in diseases such as prostate cancer, ovarian cancer, and colorectal cancer.

Orlistat promotes tumor cell apoptosis through several mechanisms. It downregulates the NF-κB pathway, inhibiting STAT3 and EMT-related proteins to decrease proliferation and inflammation in colorectal and prostate cancers. The drug activates caspase cascades, leading to increased expression of cleaved caspase-3 and caspase-9 to induce programmed cell death in ovarian and prostate malignancies. Orlistat inhibits the AKT/mTOR pathway, reducing phosphorylated AKT and downstream targets such as p70S6K and 4E-BP1, particularly in ovarian and endometrial cancers. Additionally, it upregulates TRAIL sensitivity by increasing DR5 receptor expression and reactive oxygen species production, selectively inducing apoptosis in hormone-refractory prostate cancer cells while sparing healthy tissue.

Fig. 1 Potential molecular mechanisms of orlistat mediated tumor cells apoptosis. (Hao X, et al. 2023)

References

Hao X, et al. Pharmacological effect and mechanism of orlistat in anti-tumor therapy: A review. Medicine. 2023, 102(36): e34671.

Researchers encapsulated Orlistat (ORL) in disulfide cross-linked micellar nanoparticles (nano-ORL) using the evaporation method to overcome its poor solubility. Nanoparticles were characterized via TEM and DLS, confirming uniform spherical morphology (~18 nm) and near-neutral zeta potential. In vitro experiments used PC-3 prostate cancer cells and RWPE-1 normal prostate epithelial cells. MTT assays demonstrated nano-ORL’s enhanced dose-dependent cytotoxicity in PC-3 cells versus minimal effects on RWPE-1 cells. Flow cytometry with PI staining revealed nano-ORL significantly increased apoptosis rates dose-dependently. Cell cycle analysis showed nano-ORL induced G0/G1 phase arrest at 24h. Confocal microscopy with Hoechst 33342 staining confirmed apoptotic morphology in PC-3 cells. Western blot analysis demonstrated nano-ORL’s mechanism: downregulation of FASN expression and upregulation of pro-apoptotic markers caspase-3, Bax, and PARP cleavage. Synergistic effects were observed when combining nano-ORL with paclitaxel nanoparticles. Control treatments (DMSO and empty micelles) showed no cytotoxicity. Statistical analysis used Student’s t-test with significance at p<0.05. These experiments collectively demonstrated that nanoencapsulation enhanced ORL’s solubility, selective cytotoxicity, and apoptotic induction in cancer cells through FASN inhibition and apoptosis pathway activation.

Fig. 2 Cytotoxicity evaluation of nano-ORL in PC-3 cells treated with different concentrations. (Armutcu F, Adam B. 2024)

References

Armutcu F, Adam B. The effect of nano-encapsulated orlistat on prostate cancer: an in vitro study. Journal of Nanotechnology and Nanomaterials. 2024, 5(1): 7-14.

Can Orlistat be exposed to high humidity during long-term storage?

No, Orlistat is moisture-sensitive and must be kept in a dry environment.

Does Orlistat require protection from light in the warehouse?

Yes, keep Orlistat away from direct sunlight to prevent potential chemical degradation.

How can I obtain a current price list for Orlistat?

Please send an inquiry with your required volume to receive an Orlistat quote.

Does a certificate of analysis accompany the Orlistat shipment?

Every batch of Orlistat is shipped with a corresponding Certificate of Analysis.