Home Apoptosis IAP antagonist SM-164 For research use only.

SM-164

SM-164 is a potent, non-peptide, cell-permeable antagonist of XIAP that targets both the BIR2 and BIR3 domains with IC50 of 1.39 nM. SM-164 induces apoptosis and tumor regression.

SM-164 Chemical Structure

SM-164 Chemical Structure

CAS No. 957135-43-2

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SM-164 Related Products

Signaling Pathway

IAP Signaling Pathways

IAP Signaling Pathway

Biological Activity

Description SM-164 is a potent, non-peptide, cell-permeable antagonist of XIAP that targets both the BIR2 and BIR3 domains with IC50 of 1.39 nM. SM-164 induces apoptosis and tumor regression.
Features The potency of bivalent SM-164 in binding, functional, and cellular assays is 2−3 orders of magnitude higher than its corresponding monovalent Smac mimetics.
Targets
XIAP [1]
(Cell-free assay)
1.39 nM
In vitro
In vitro

SM-164 binds to XIAP containing both BIR domains with IC50 of 1.39 nM, being 300 and 7000 times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. SM-164 targets cellular XIAP and effectively induces apoptosis at concentrations as low as 1 nM in the HL-60 leukemia cell line. [1]

SM-164 induces caspase-8– and caspase-3–dependent apoptosis in cancer cells. SM-164 induces TNFα-dependent apoptosis and cIAP-1 degradation. [2]

SM-164 is highly synergistic with TRAIL in vitro in both TRAIL-sensitive and TRAIL-resistant cancer cell lines of breast, prostate, and colon cancer. SM-164 enhances TRAIL-induced apoptosis in cancer cells through amplification of the caspase-8–mediated extrinsic apoptosis pathway [3]
Kinase Assay Binding assays.
The FP-based assay for XIAP BIR3 protein is described. Briefly, 5-carboxyfluorescein is coupled to the lysine side chain of a mutated Smac peptide with the sequence and this fluorescently tagged peptide (named SM5F) is used as the fluorescent tracer in FP-based binding assay to XIAP BIR3. The Kd value of this fluorescent tracer is determined to be 17.9 nM to XIAP BIR3. In competitive binding experiments, a tested compound is incubated with 30 nM ofXIAP BIR3 protein and 5 nM of SM5F in the assay buffer (100 mM potassium phosphate, pH 7.5; 100 μg/ml bovine gamma globulin; 0.02 % sodium azide). The Kd value of SM5F to cIAP-1 BIR3 protein is determined to be 4.1 nM. In competitive binding experiments, 10 nM of cIAP-1 BIR3 protein and 2 nM of SM5F tracer are used. The Kd value of SM5F to cIAP-2 BIR3 protein is determined to be 6.6 nM. In competitive binding experiments, 25 nM of cIAP-2 BIR3 proteinand 2 nM of SM5F tracer are used. To determine the binding affinities of Smac mimetics to XIAP containing both BIR2 and BIR3 domains, an FP-based competitive binding assay is established using a bivalentfluorescently tagged tracer, named Smac-1F. The Kd value of the bivalent tagged tracer to XIAP containing BIR2 and BIR3 domains is determined to be 2.3 nM. In competitive binding experiments, a tested compound is incubated with 3 nM of XIAP protein containing both BIR2 and BIR3 domain (residues 120-356) and 1 nM of in the sameassay buffer.
Cell Research Cell lines HT-29 cells
Concentrations 1 μM
Incubation Time 6 or 12 h
Method

Cells pre-treated with HG (5 μM) for 30 min were treatment with SM-164 (1 μM) for 6 or 12 h.
In Vivo
In vivo

SM-164 induces rapid cIAP-1 degradation and strong apoptosis in the MDA-MB-231 xenograft tumor tissues and achieves tumor regression, but has no toxicity in normal mouse tissues. [2]

SM-164 induces cIAP1 degradation in tumor tissues and dramatically enhances the in vivoantitumor activity of TRAIL, and the combination of SM-164 and TRAIL achieves tumor regression without toxicity to animals. [3]
Animal Research Animal Models MDA-MB-231 xenografted SCID mice
Dosages 1 and 5 mg/kg
Administration i.v.

Chemical Information & Solubility

Molecular Weight 1121.42 Formula

C62H84N14O6
CAS No. 957135-43-2 SDF --
Smiles CC(C(=O)NC1CCCCC2CCC(N2C1=O)C(=O)NC(C3=CC=CC=C3)C4=CN(N=N4)CCCCC5=CC=C(C=C5)CCCCN6C=C(N=N6)C(C7=CC=CC=C7)NC(=O)C8CCC9N8C(=O)C(CCCC9)NC(=O)C(C)NC)NC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 3 mg/mL ( (2.67 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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