IACS-010759

OxPhos complex I inhibitor

Also Known As:

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; 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)-

Networked: 27 relevant articles (2 outcomes, 4 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Heterocyclic Compounds: 198
- 1-Ring Heterocyclic Compounds
  - Azoles: 2138
    - Oxazoles: 89
      - Oxadiazoles: 146
        IACS-010759: 27
  - Piperidines: 17
    - IACS-010759: 27

Experts

1.	Marszalek, Joseph R: 10 articles (01/2022 - 01/2018)
2.	Feng, Ningping: 4 articles (01/2022 - 01/2018)
3.	Konopleva, Marina: 4 articles (01/2022 - 01/2018)
4.	Di Francesco, M Emilia: 4 articles (01/2021 - 01/2018)
5.	Sun, Yuting: 4 articles (11/2019 - 01/2018)
6.	Lorenzi, Philip L: 3 articles (02/2022 - 01/2019)
7.	Gay, Jason: 3 articles (01/2022 - 01/2018)
8.	Lodi, Alessia: 3 articles (01/2022 - 01/2018)
9.	Tiziani, Stefano: 3 articles (01/2022 - 01/2018)
10.	Davies, Michael A: 3 articles (01/2020 - 01/2019)

Related Diseases

1.	Neoplasms (Cancer) 05/05/2023 - "Among them, IACS-010759 had been approved by FDA for phase I trial in advanced cancers. " 01/01/2022 - "We examined the impact of the ETC complex I inhibitor IACS-010759 on tumor 13C labeling. " 01/01/2021 - "Here, we present a 3.0-Å resolution cryo-electron microscopy structure of mammalian complex I inhibited by a derivative of IACS-010759, which is currently in clinical development against cancers reliant on oxidative phosphorylation, revealing its unique cork-in-bottle mechanism of inhibition. " 01/01/2018 - "IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors." 01/01/2023 - "Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). "
2.	Melanoma (Melanoma, Malignant) 01/01/2019 - "IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor-resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. " 02/22/2022 - "We recently showed that a novel electron transport chain (ETC) complex I inhibitor, IACS-010759 (IACS), abolished OxPhos and significantly inhibited tumor growth of high-OxPhos, BRAF inhibitor (BRAFi)-resistant human melanomas. " 11/21/2019 - "Notably, in an OxPhos-reliant melanoma tumor, a titration curve using [18F]FAZA PET retention in vivo yielded an IC50 for IACS-010759 (1.4 mg/kg) equivalent to analysis ex vivo. "
3.	Acute Myeloid Leukemia (Acute Myelogenous Leukemia) 01/01/2021 - "The Combined Treatment With the FLT3-Inhibitor AC220 and the Complex I Inhibitor IACS-010759 Synergistically Depletes Wt- and FLT3-Mutated Acute Myeloid Leukemia Cells." 01/01/2023 - "Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). " 07/01/2023 - "One of the OXPHOS inhibitor drugs, IACS-010759, developed by investigators at MD Anderson Cancer Center, was tested in patients with acute myeloid leukemia. " 01/01/2018 - "Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. "
4.	Leukemia 11/21/2019 - "In this regard, IACS-010759 is a novel high affinity inhibitor of OxPhos targeting mitochondrial complex-I that has recently completed a Phase-I clinical trial in leukemia. " 08/24/2020 - "In this study, we show that IACS-010759 and venetoclax synergistically induce apoptosis in OXPHOS-reliant AML cell lines and primary patient samples and cooperatively target leukemia progenitor cells. "
5.	Peripheral Nervous System Diseases (PNS Diseases) 01/01/2023 - "Reverse translational studies in mice demonstrated that IACS-010759 induced behavioral and physiological changes indicative of peripheral neuropathy, which were minimized with the coadministration of a histone deacetylase 6 inhibitor. "

Related Drugs and Biologics

1.	Sunitinib (Sutent)
2.	talazoparib
3.	venetoclax
4.	Histones (Histone)
5.	Electron Transport Complex I (NADH-CoQ Reductase)
6.	Holoenzymes
7.	Biomarkers (Surrogate Marker)
8.	Nucleotides
9.	Glutamine (L-Glutamine)
10.	Enzymes

Related Therapies and Procedures

1.	Radiotherapy
2.	Drug Therapy (Chemotherapy)