AZD1208 hydrochloride

Modify Date: 2024-01-14 10:55:27

AZD1208 hydrochloride structure	Common Name	AZD1208 hydrochloride
	CAS Number	1621866-96-3	Molecular Weight	415.94
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₂₁H₂₂ClN₃O₂S	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of AZD1208 hydrochloride

AZD1208 hydrochloride is a novel, orally bioavailable, highly selective PIM kinases inhibitor.

Name	AZD1208 hydrochloride

Description	AZD1208 hydrochloride is a novel, orally bioavailable, highly selective PIM kinases inhibitor.
Related Catalog	Signaling Pathways >> JAK/STAT Signaling >> Pim Research Areas >> Neurological Disease
Target	PIM[1]
In Vitro	AZD1208 hydrochloride shows good antiproliferative activity in a megakaryoblastic leukemia cell line, MOLM-16, with GI50 values less than 100 nM[1]. AZD1208 hydrochloride (10 μM) inhibits the growth of Ramos cells, and at 1 μM, strongly inhibits PIM kinases in all cells at 1 μM. AZD1208 hydrochloride induces apoptosis, and PIM2 knockdown is mainly associated with an alteration of the cell cycle[2]. The combination of AZD1208 hydrochloride and AZD2014 rapidly activates AMPKα, a negative regulator of translation machinery through mTORC1/2 signaling in AML cells; profoundly inhibits AKT and 4EBP1 activation; and suppresses polysome formation[3].
Kinase Assay	The activity of purified human PIM-1, PIM-2 and PIM-3 enzymes on substrate FL-Ahx-Bad is determined using a mobility shift assay on a reader. The PIM-1 assay is performed in a 12 mL reaction containing 50 mM HEPES (pH 7.5), 1 mM DTT, 0.01% Tween 20, 50 mg/mL BSA, 10 mM MgCl2, 1.5 mM FL-Ahx-Bad peptide, 100 mM ATP, 2.5 nM PIM-1 and various amount of inhibitor. The reaction is quenched after 90 minute incubation at 25˚C with 5 mL of stop mix consisting of 100 mM HEPES, 121 mM EDTA, 0.8% Coating Reagent 3 and 0.01% Tween 20. The ATP and enzyme concentrations for the PIM-2 assay are 5 mM and 2.5 nM, respectively, while 50 mM of ATP and 0.33 nM of enzyme is used for PIM-3 assays. For high [ATP] screenings, 5 mM ATP is used with 0.67 nM enzyme for both PIM-1 and PIM-2 or 0.11 nM PIM-3. Fluorescence of phosphorylated and unphosphorylated substrate is detected and a ratiometric value is calculated to determine percent turnover. IC50 values are determined from dose-response data using software[1].
Cell Assay	MOLM-16 cells, purchased from DSMZ and cultured in RPMI containing 10% fetal bovine serum (FBS) and 1% L-glutamine, are plated at 20,000 cells per well in 96 well plates overnight. Cells are treated for 72 hours with compound (including AZD1208 hydrochloride) or control vehicle (dimethyl sulfoxide) and cell viability is measured after the addition of Cell Titer-Blue for 4 hours at 37˚C and reading of fluorescence on a Tecan Infinite® 200. The GI50 is determined by calculating growth at each dose relative to vehicle treated cells and cell viability at the time of treatment[1].
References	[1]. Dakin LA, et al. Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4599-604. [2]. Kreuz S, et al. Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas. Mol Cancer. 2015 Dec 8;14:205. [3]. Harada M, et al. The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression. Oncotarget. 2015 Nov 10;6(35):37930-47.

Molecular Formula	C₂₁H₂₂ClN₃O₂S
Molecular Weight	415.94
Storage condition	2-8℃