[CAS NO. 1353858-99-7] CX-6258hydrochloridehydrate
PRODUCTS SPECIFICATIONS [1353858-99-7]
DESCRIPTION [1353858-99-7]
Overview
| MDL | MFCD26142938 |
|---|---|
| Molecular Weight | 516.42 |
| Molecular Formula | C26H27Cl2N3O4 |
| SMILES | O=C1NC2=CC=C(Cl)C=C2/C1=C\C3=CC=C(C4=CC=CC(C(N5CCCN(C)CC5)=O)=C4)O3.[H]Cl.O |
Summary
CX-6258 hydrochloride hydrate is a potent and kinase selective pan-Pim kinases inhibitor, with IC 50 s of 5 nM, 25 nM and 16 nM for Pim-1, Pim-2 and Pim-3, respectively [1] .
IC50 & Target
IC50: 5 nM (Pim-1), 25 nM (Pim-2), 16 nM (Pim-3) [1]
In Vitro
CX-6258 causes dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively
[1]
.
CX-6258 treatment (12 mM, 3 h) treatment diminishes steady-state levels of ectopic NKX3.1 in PC3 cells
[2]
.
CX-6258 treatment results in a significant reduction in NKX3.1 half-life
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1]
| Cell Line: | MV-4-11 human AML cells. |
| Concentration: | 0.1 μM, 1 μM, 10 μM. |
| Incubation Time: | 2 hours. |
| Result: | Caused dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively. |
In Vivo
CX-6258 (50-100 mg/kg; p.o; daily; over a period of 21 days) exhibits robust in vivo efficacy in two Pim kinases driven tumor models
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Nude mice, MV-4-11 xenograft models [1] |
| Dosage: | 50 mg/kg, 100 mg/kg. |
| Administration: | Oral administration; once daily; over a period of 21 days. |
| Result: | Exhibited dose dependent efficacy, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI. |
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 : 25 mg/mL ( 48.41 mM ; Need ultrasonic)
H 2 O : 7.14 mg/mL ( 13.83 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9364 mL | 9.6820 mL | 19.3641 mL |
| 5 mM | 0.3873 mL | 1.9364 mL | 3.8728 mL |
| 10 mM | 0.1936 mL | 0.9682 mL | 1.9364 mL |
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1.
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.84 mM); Clear solution
References
- [1] Mustapha Haddach, Jerome Michaux, Michael K, Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor. ACS Med. Chem. Lett., 2012, 3 (2), pp 135-139
- [2] Padmanabhan A, Gosc EB, Bieberich CJ. Stabilization of the prostate-specific tumor suppressor NKX3.1 by the oncogenic protein kinase Pim-1 in prostate cancer cells. J Cell Biochem. 2013 May;114(5):1050-7.
