[CAS NO. 1807523-99-4] IACS-010759hydrochloride
PRODUCTS SPECIFICATIONS [1807523-99-4]
DESCRIPTION [1807523-99-4]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 599.02 |
| Molecular Formula | C25H26ClF3N6O4S |
| SMILES | FC(F)(F)OC1=CC=C(C2=NOC(C3=NN(CC4=CC(N5CCC(S(=O)(C)=O)CC5)=CC=C4)C(C)=N3)=N2)C=C1.Cl |
3 Publications Citing Use of MCE
Summary
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 [1] [2] .
IC50 & Target
OXPHOS [1]
In Vitro
IACS-010759 hydrochloride (10, 30, 100 nM; for 4 or 5 days) reduces viability and induces apoptosis in primary AML
[1]
.
IACS-010759 hydrochloride (0.001, 0.01, 0.1, 1, 10, 100, 1000 nM; 72 hurs) robustly inhibits both OCR and galactose-dependent H460 cell viability and has nearly identical IC50 values of 1.4 nM
[1]
.
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
[1]
.
IACS-010759 hydrochloride (0.01-10 μM) yieldes a maximal reduction of growth of > 50% in the majority of cancer cell lines (24 of 30 pancreatic (PDAC), 19 of 20 ovarian, 13 of 16 triple-negative breast (TNBC), 8 of 10 non-small-cell lung (NSCLC)) and a subset (11of 30 PDAC, 10 of 20 ovarian, 5 of 16 TNBC, 2 of 10 NSCLC) exhibited > 100% growth inhibition
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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
[1]
.
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
[1]
.
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)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03291938 | M.D. Anderson Cancer Center|National Cancer Institute (NCI) |
Advanced Malignant Solid Neoplasm|Anatomic Stage III Breast Cancer AJCC v8|Anatomic Stage IIIA Breast Cancer AJCC v8|Anatomic Stage IIIB Breast Cancer AJCC v8|Anatomic Stage IIIC Breast Cancer AJCC v8|Anatomic Stage IV Breast Cancer AJCC v8|Estrogen Receptor Negative|HER2+Neu Negative|Metastatic Malignant Solid Neoplasm|Pancreatic Ductal Adenocarcinoma|Progesterone Receptor Negative|Prognostic Stage III Breast Cancer AJCC v8|Prognostic Stage IIIA Breast Cancer AJCC v8|Prognostic Stage IIIB Breast Cancer AJCC v8|Prognostic Stage IIIC Breast Cancer AJCC v8|Prognostic Stage IV Breast Cancer AJCC v8|Recurrent Lymphoma|Refractory Lymphoma|Stage II Pancreatic Cancer AJCC v8|Stage IIA Pancreatic Cancer AJCC v8|Stage IIB Pancreatic Cancer AJCC v8|Stage III Pancreatic Cancer AJCC v8|Stage IV Pancreatic Cancer AJCC v8|Triple-Negative Breast Carcinoma|Unresectable Solid Neoplasm
|
November 13, 2017 | Phase 1 |
| NCT02882321 | M.D. Anderson Cancer Center|National Cancer Institute (NCI) |
Recurrent Acute Myeloid Leukemia|Refractory Acute Myeloid Leukemia
|
September 29, 2016 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 60 mg/mL ( 100.16 mM ; Need ultrasonic)
H 2 O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.6694 mL | 8.3470 mL | 16.6939 mL |
| 5 mM | 0.3339 mL | 1.6694 mL | 3.3388 mL |
| 10 mM | 0.1669 mL | 0.8347 mL | 1.6694 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.17 mM); Clear solution
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. Ph
- [2] Jennifer R Molina, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med. 2018 Jul;24(7):1036-1046.
