1. Apoptosis
  2. IAP

SM-164 Hydrochloride 

Cat. No.: HY-15989A
Handling Instructions

SM-164 Hydrochloride is a cell-permeable Smac mimetic compound. SM-164 binds to XIAP protein containing both the BIR2 and BIR3 domains with an IC50 value of 1.39 nM and functions as an extremely potent antagonist of XIAP.

For research use only. We do not sell to patients.
SM-164 Hydrochloride Chemical Structure

SM-164 Hydrochloride Chemical Structure

Size Price Stock Quantity
10 mM * 1 mL in Water USD 764 In-stock
5 mg USD 420 In-stock
10 mg USD 600 In-stock
50 mg USD 1800 In-stock
100 mg   Get quote  
200 mg   Get quote  

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Other Forms of SM-164 Hydrochloride:

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  • Biological Activity

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  • Technical Information

  • Purity & Documentation

  • References

Description

SM-164 Hydrochloride is a cell-permeable Smac mimetic compound. SM-164 binds to XIAP protein containing both the BIR2 and BIR3 domains with an IC50 value of 1.39 nM and functions as an extremely potent antagonist of XIAP.

IC50 & Target

IC50: 1.39 nM (XIAP)[1]
Ki: 0.56 nM to (XIAP), 0.31 nM to (cIAP-1), 1.1 nM (cIAP-2)[2]

In Vitro

SM-164 is a non-peptide, cell-permeable, bivalent small-molecule, which mimics Smac protein for targeting XIAP. SM-164 binds to XIAP containing both BIR domains with an IC50 value of 1.39 nM, being 300 and 7000-times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. SM-164 concurrently interacts with both BIR domains in XIAP and functions as an ultra-potent antagonist of XIAP in both cell-free functional and cell-based assays. SM-164 targets cellular XIAP and effectively induces apoptosis at concentrations as low as 1 nM in leukemia cancer cells, while having a minimal toxicity to normal human primary cells at 10,000 nM[1]. The binding affinities of SM-164 to XIAP, cIAP-1, and cIAP-2 proteins are determined using fluorescence-polarization based assays. SM-164 has a Ki value of 0.56 nM to XIAP protein containing both BIR2 and BIR3 domains. SM-164 has a Ki value of 0.31 nM to cIAP-1 protein containing both BIR2 and BIR3 domains. SM-164 binds to cIAP-2 BIR3 protein with Ki values of 1.1 nM. Addition of exogenous TNFα can significantly enhance the activity of these Smac mimetics, especially for SM-164, in resistant cancer cell lines such as HCT116 and MDA-MB-453[2].

In Vivo

SM-164 is evaluated for its ability to inhibit tumor growth. SM-164 is highly effective in inhibition of tumor growth and capable of achieving tumor regression in the MDA-MB-231 xenograft model. Treatment with SM-164 at 1 mg/kg completely inhibits tumor growth during the treatment. Treatment with SM-164 at 5 mg/kg reduces the tumor volume from 147±54 mm3 at the beginning of the treatment (day 25) to 54±32 mm3 at the end of the treatment (day 36), a reduction of 65%. The strong antitumor activity by SM-164 is long lasting and not transient. SM-164 at 5 mg/kg is statistically more effective than Taxotere at the end of the treatment (P<0.01) or when the tumor size in the control group reached 750 mm3 (P<0.02)[2].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 0.8636 mL 4.3182 mL 8.6365 mL
5 mM 0.1727 mL 0.8636 mL 1.7273 mL
10 mM 0.0864 mL 0.4318 mL 0.8636 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[2]

A set of sensitive and quantitative fluorescence polarization (FP)-based assays are developed to determine the binding affinities of our designed Smac mimetics to XIAP BIR3, XIAP containing both BIR2 and BIR3 domains, cIAP-1 BIR3, cIAP-1 containing both BIR2 and BIR3 domains, and cIAP-2 protein. The FP-based assay for XIAP BIR3 protein is measured. Briefly, 5-carboxyfluorescein is coupled to the lysine side chain of a mutated Smac peptide with the sequence (AbuRPFK-Fam) 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 of XIAP BIR3 protein and 5 nM of SM5F in the assay buffer (100 mM potassium phosphate, pH 7.5; 100μg/mL bovine gamma globulin; 0.02 % sodium azide)[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

HCT116 colon cancer cells are treated with SM-164 (1, 10, and 100 nM) alone, TNFα alone, or the combination for 48 h. Cell growth inhibition is determined by a WST assay[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Mice[2]
SCID mice (8-10 per group) bearing MDA-MB-231 xenograft tumors are treated i.v. with 1 and 5 mg/kg of SM-164 or 7.5 mg/kg of Taxotere or vehicle control daily, 5 d/wk for 2 wk. Tumor sizes and animal weights are measured thrice a week[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

1157.88

Formula

C₆₂H₈₅ClN₁₄O₆

SMILES

C[[email protected]](NC)C(N[[email protected]]1CCCC[[email protected]](CC[[email protected]]2C(N[[email protected]@H](C3=CC=CC=C3)C4=CN(CCCCC5=CC=C(CCCCN6N=NC([[email protected]@H](NC([[email protected]@H]7CC[[email protected]@](CCCC[[email protected]@H]8NC([[email protected]@H](NC)C)=O)([H])N7C8=O)=O)C9=CC=CC=C9)=C6)C=C5)N=N4)=O)([H])N2C1=O)=O.Cl

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

H2O: ≥ 106 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
SM-164 Hydrochloride
Cat. No.:
HY-15989A
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