Drug Information

Drug (ID: DG02038) and It's Reported Resistant Information

• Name: Orlistat
• Synonyms: orlistat; 96829-58-2; Tetrahydrolipstatin; Xenical; Alli; Orlipastat; (-)-Tetrahydrolipstatin; Orlipastatum; Orlipastatum [INN-Latin]; THLP; Ro-18-0647; UNII-95M8R751W8; C29H53NO5; Ro 18-0647/002; N-Formyl-L-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester; (2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate; Orlistat (Alli, Xenical); MLS002207022; [(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-2-formamido-4-methylpentanoate; CHEMBL175247; Alli; GlaxoSmithKline brand of orlistat; Roche brand of orlistat; Alli (TN); Hoffmann-La Roche brand of orlistat; KS-1183; Orlistat [USAN:INN]; R-212; Xenical (TN); Orlistat (USAN/INN); Ro 18-0647/008; Alli, Xenical, Tetrahydrolipstatin, Orlistat; N-Formyl-L-leucine, ester with (3S,4S)-3-hexyl-4-((2S)-2-hydroxytridecyl)-2-oxetanone; L-Leucine, N-formyl-, (1S)-1-(((2S,3S)-3-hexyl-4-oxo-2-oxetanyl)methyl)dodecyl ester; L-Leucine,N-formyl-, (1S)-1-(((2S,3S)-3-hexyl-4-oxo-2-oxetanyl)methyl)dodecyl ester; 1-((3-hexyl-4-oxo-2-oxetanyl)methyl)dodecyl-2-formamido-4-methylvalerate; TETRAHYDROLIPSTATIN
• Indication:
  In total 1 Indication(s)
  Obesity [ICD-11: 5B80-5B81]; Approved
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Pancreatic cancer [ICD-11: 2C10]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Pancreatic cancer [ICD-11: 2C10]; [1]
• Target: Pancreatic triacylglycerol lipase (PNLIP); LIPP_HUMAN
• Formula: C29H53NO5
• IsoSMILES: CCCCCCCCCCC[C@@H](C[C@H]1[C@@H](C(=O)O1)CCCCCC)OC(=O)[C@H](CC(C)C)NC=O
• InChI: InChI=1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1
• InChIKey: AHLBNYSZXLDEJQ-FWEHEUNISA-N
• PubChem CID: 3034010
• ChEBI ID: CHEBI:94686
• TTD Drug ID: D0T9TJ

Type(s) of Resistant Mechanism of This Drug

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Pancreatic cancer [ICD-11: 2C10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Acyl-CoA thioesterase 8 (ACOT8) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude mouse subcutaneous tumorigenic models; Mice
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

Key Molecule: Acyl-CoA thioesterase 8 (ACOT8) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AsPC1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• In Vitro Model: MiaPaCa-2 cells; Blood; Homo sapiens (Human); CVCL_0428
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

Key Molecule: Acyl-CoA thioesterase 8 (ACOT8) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic ductal adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.82E-14; Fold-change: 6.86E-01; Z-score: 8.55E+00
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Patient-derived PDAC organoids; Homo Sapiens
• Experiment for Molecule Alteration: Transcriptome sequencing and analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines.

References

• Ref 1: Acyl-CoA thioesterase 8 induces gemcitabine resistance via regulation of lipid metabolism and antiferroptotic activity in pancreatic ductal adenocarcinoma. Acta Pharmacol Sin. 2025 Feb 12.