Drug Information

Drug (ID: DG02015) and It's Reported Resistant Information

• Name: IACS-010759
• Synonyms: 1570496-34-2|IACS-010759|IACS-10759|5-(5-methyl-1-(3-(4-(methylsulfonyl)piperidin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole|IACS-010759 free base|IACS 010759 - Bio-X|IACS 010759 [WHO-DD]|Iacs 010759|5-[5-methyl-1-[[3-(4-methylsulfonylpiperidin-1-yl)phenyl]methyl]-1,2,4-triazol-3-yl]-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole|42W52V11DJ|Oxidative phosphorylation inhibitor IACS-010759|1570496-34-2 (free base)|IACS-010759 (IACS-10759)|4-Methanesulfonyl-1-{3-[(5-methyl-3-{3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}-1H-1,2,4-triazol-1-yl)methyl]phenyl}piperidine|Piperidine, 4-(methylsulfonyl)-1-(3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)phenyl)-|4-(Methylsulfonyl)-1-[3-[[5-methyl-3-[3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]-1H-1,2,4-triazol-1-yl]methyl]phenyl]piperidine (IACS-010759)|UNII-42W52V11DJ|C25H25F3N6O4S|CHEMBL4778699|SCHEMBL15498716|IACS10759|GLXC-15124|BCP20596|EX-A1907|OXPHOS Inhibitor IACS-010759|IACS-010759?|NSC809972|s8731|AKOS030527987|NSC-809972|AC-31606|BS-15465|FM165719|DB-196077|HY-112037|CS-0042459|C72972|4-(Methylsulfonyl)-1-(3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)phenyl)piperidine|4-(Methylsulfonyl)-1-[3-[[5-methyl-3-[3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]-1H-1,2,4-triazol-1-yl]methyl]phenyl]piperidine (IACS-010759); 4-(Methylsulfonyl)-1-[3-[[5-methyl-3-[3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]-1H-1,2,4-triazol-1-yl]methyl]phenyl]piperidine (IACS-010759)|4-methanesulfonyl-1-{3-[(5-methyl-3-{3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}-1,2,4-triazol-1-yl)methyl]phenyl}piperidine|4-Methanesulfonyl-1-{3-[(5-methyl-3-{3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}-1H-1,2,4-triazol-1-yl)methyl]phenyl}piperi dine
• Indication:
  In total 1 Indication(s)
  . .; .
• Formula: C25H25F3N6O4S
• IsoSMILES: CC1=NC(=NN1CC2=CC(=CC=C2)N3CCC(CC3)S(=O)(=O)C)C4=NC(=NO4)C5=CC=C(C=C5)OC(F)(F)F
• InChI: InChI=1S/C25H25F3N6O4S/c1-16-29-23(24-30-22(32-38-24)18-6-8-20(9-7-18)37-25(26,27)28)31-34(16)15-17-4-3-5-19(14-17)33-12-10-21(11-13-33)39(2,35)36/h3-9,14,21H,10-13,15H2,1-2H3
• InChIKey: HWJWNWZJUYCGKV-UHFFFAOYSA-N
• PubChem CID: 86711931

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

Prostate cancer [ICD-11: 2C82]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Cyclin-dependent kinase 12 (CDK12) [1]

• Metabolic Type: Mitochondrial metabolism
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude (nu/nu) mice, with PC3 VEC or PC3 CDK12KO; Mice
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: CDK12-deficient prostate cancers reprogramme cellular energy metabolism to support their aggressive progression. In particular, CDK12 deficiency enhanced the mitochondrial respiratory chain for electronic transfer and ATP synthesis to create a ferroptosis potential in CRPC cells. However, CDK12 deficiency downregulated ACSL4 expression, which counteracts the lipid oxidation stress, leading to the escape of CRPC cells from ferroptosis.

Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]

• Metabolic Type: Mitochondrial metabolism
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: .; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PNT1A cells; Prostate; Homo sapiens (Human); CVCL_2163
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [25]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]

• Metabolic Type: Mitochondrial metabolism
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: .; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [26]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]

• Metabolic Type: Mitochondrial metabolism
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: .; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PC-3 cells; Bone; Homo sapiens (Human); CVCL_0035
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [27]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]

• Metabolic Type: Mitochondrial metabolism
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: .; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [28]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.

References

• Ref 1: Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer. Clin Transl Med. 2024 May;14(5):e1678.
• Ref 2: Mitochondrial Elongation and ROS-Mediated Apoptosis in Prostate Cancer Cells under Therapy with Apalutamide and Complex I Inhibitor. Int J Mol Sci. 2024 Jun 25;25(13):6939.