IACS-010759 hydrochloride

SKU: orb1700376

Description

IACS-010759 hydrochloride is a potent, selective, and orally bioavailable OXPHOS inhibitor. It suppresses proliferation and promotes apoptosis in OXPHOS-dependent cancers, including models of AML and glioblastoma, making it a valuable tool for studying relapsed/refractory malignancies in both in vitro and in vivo experimental settings.

Research Area

Cell Biology, Metabolism Research

Key Properties

• CAS Number: 1807523-99-4
• MW: 599.03
• Purity: 98.81% (May vary between batches)
• Formula: C₂₅H₂₆ClF₃N₆O₄S
• SMILES: Cl.O=S(=O)(C)C1CCN(C2=CC=CC(=C2)CN3N=C(N=C3C)C4=NC(=NO4)C=5C=CC(OC(F)(F)F)=CC5)CC1
• Target: Mitochondrial Metabolism,Apoptosis,OXPHOS
• Solubility: DMSO:50 mg/mL (83.47 mM);2% DMSO+40% PEG300+5% Tween 80+53% Saline:1 mg/mL (1.67 mM);H2O:< 1 mg/mL (insoluble)

Bioactivity

• Target IC50:
  Mitochondrial oxidative phosphorylation (Mouse primary cells):5.6 nM|Mitochondrial oxidative phosphorylation (H460 cells):1.4 nM (72 h)|Mitochondrial oxidative phosphorylation (AML patient-derived cells):10-100 nM (4-5 days)|Mitochondrial oxidative phosphorylation (Rat primary cells):12.2 nM|Mitochondrial oxidative phosphorylation (Cynomolgus monkey primary cells):8.7 nM
• In Vivo:
  In NB-1 neuroblastoma xenograft mice, oral IACS-010759 hydrochloride at 5-10 mg/kg for 21 days significantly reduced tumor size, although 25 mg/kg was not well tolerated. In another model, daily or alternate-day dosing at 10 mg/kg for 35 days extended survival from 28 to over 60 days, and lower-frequency dosing (e.g., 2×/week) also improved outcomes. Pharmacokinetic studies showed that a 0.3 mg/kg dose had low clearance, limited distribution, and a prolonged half-life (>24 h).
• In Vitro:
  IACS-010759 hydrochloride shows potent in vitro activity by reducing AML cell viability and inducing apoptosis at concentrations of 10-100 nM over 4-5 days. It also inhibits mitochondrial OCR and oxidative phosphorylation-dependent viability in H460 cells, with an average IC₅₀ of 1.4 nM over 72 h. Similar potency was observed in cells from mice (IC₅₀ = 5.6 nM), rats (12.2 nM), and cynomolgus monkeys (8.7 nM).

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

IACS 010759, IACS 010759 hydrochloride, IACS 010759 Hydrochloride, IACS 10759, IACS010759, IACS-010759, IACS010759 HCl, IACS-010759 HCl, IACS010759 hydrochloride, IACS010759 Hydrochloride, IACS-010759 Hydrochloride, IACS10759, IACS-10759, IACS10759 hydrochloride, IACS-10759 hydrochloride

Compound Identifiers

PubChem CID

91864637