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IACS-010759 HCl salt form · salt · Parent IACS-10759 · Synonyms: IACS-10759 Hydrochloride

IACS-010759 hydrochlorideis an orally active, potent mitochondrial complex I of oxidative phosphorylation (OXPHOS) inhibitor.

For research use only. Not for human or veterinary use.

Target Oxidative Phosphorylation Mitochondrial Metabolism Apoptosis
Research area Cancer
Purity >98% Stock Inquire
Data Sheet SDS COA

IACS-010759 HCl structure

CAS No.: 1807523-99-4

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
100 mg USD 495.00 BP-01900A-100mg In stock Get quote
250 mg USD 895.00 BP-01900A-250mg In stock Get quote
500 mg USD 1,395.00 BP-01900A-500mg In stock Get quote
1 g Inquire BP-01900A-1g In stock Inquire
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Description

IACS-010759 hydrochlorideis an orally active, potent mitochondrial complex I of oxidative phosphorylation (OXPHOS) inhibitor. IACS-010759 hydrochlorideinhibits proliferation and induces apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS. IACS-010759 hydrochloride has the potential for relapsed/refractory AML and solid tumors research.

Biological activity

In Vitro IACS-010759 hydrochloride (4 or 5 days) reduces viability and induces apoptosis in primary AML. IACS-010759 hydrochloride (72 hurs) robustly inhibits both OCR and galactose-dependent H460 cell viability and has nearly identical IC50 values of 1.4?nM. IACS-010759 hydrochlorideis similarly active in mouse (average IC50?=?5.6?nM), rat (IC50?=?12.2?nM), and cynomolgus monkey (IC50?=?8.7?nM) cell lines. In Vivo IACS-010759 hydrochloride (5, 10, 25?mg/kg/day; oral; for 21 d) results in tumor regression with minimal body weight loss at the 5 or 10?mg/kg dose in mice bearing NB-1 (PGD-null) subcutaneous xenografts. IACS-010759 at the 25?mg/kg dose is not tolerated. IACS-010759 HCl (10?mg/kg; orally; QD (daily) or QD×5 (5 d on/2 d off); for 35 d) increases median survival from 28 d to longer than 60 d, whereas less-frequent dosing schedules (Q2D or Q3D) enhances survival to a lesser extent. IACS-010759 hydrochloride (0.3?mg/kg for iv; 1?mg/kg for oral) has low plasma clearance with a high volume of distribution, resulting in a prolonged terminal half-life (>24?h).

Identifiers

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
InChIKey
LUSCFOVOISLXTM-UHFFFAOYSA-N

Specifications

MW (average)
599.0250
Formula
C25H26ClF3N6O4S
CAS No.
1807523-99-4
Physical state
Solid
Color
white to off-white
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
4°C, sealed storage, away from moisture

Solubility

Soluble in DMSO : 60 mg/mL H2O : < 0.1 mg/mL

Documents

References

[1]. Protopopova M. IACS-10759: A novel OXPHOS inhibitor which selectively kill tumors with metabolic vulnerabilities. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4380. doi:10.1158/1538-7445.AM2015-4380.
[2]. Jennifer R Molina, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med. 2018 Jul;24(7):1036-1046.

Same target

Search Oxidative Phosphorylation

Same research area

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