SM-164

Alias: SM 164; SM-164; SM164
Cat No.:V10594 Purity: ≥98%
SM-164 is a potent cell-permeable and bivalent Smac mimetic which bind to a XIAP protein and binds to cIAP-1 and cIAP-2 proteins.
SM-164 Chemical Structure CAS No.: 957135-43-2
Product category: IAP
This product is for research use only, not for human use. We do not sell to patients.
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25mg
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

SM-164 is a potent cell-permeable and bivalent Smac mimetic which bind to a XIAP protein and binds to cIAP-1 and cIAP-2 proteins. It is being developed as a cancer-fighting agent. Cellular inhibitor of apoptosis protein (cIAP)-1/2 is degraded, X-linked inhibitor of apoptosis protein (XIAP) is inhibited, and TNFα-dependent apoptosis is induced in tumor cells as a result of this compound's antitumor effects. Two SM-122 analogues make up the bivalent mimetic SM-164. It binds to proteins called XIAP and cIAP-1 that both have BIR2 and BIR3 domains as well as BIR3 protein in cIAP-2 and cIAP-1, as well as BIR2 and BIR3 domains in cIAP-2.

Biological Activity I Assay Protocols (From Reference)
Targets
cIAP-1 (Ki = 0.31 nM); cIAP-2 (Ki = 1.1 nM); cIAP
ln 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. At concentrations as low as 1 nM, SM-164 effectively induces apoptosis in the HL-60 leukemia cell line by targeting cellular XIAP.[1]
SM-164 causes caspase-8 and caspase-3-dependent apoptosis in cancer cells. SM-164 induces TNFα-dependent apoptosis and cIAP-1 degradation.[2]
In vitro, SM-164 and TRAIL work very well together against breast, prostate, and colon cancer cell lines that are both TRAIL-sensitive and TRAIL-resistant. Through amplification of the caspase-8-mediated extrinsic apoptosis pathway, SM-164 increases TRAIL-induced apoptosis in cancer cells. [3]
ln Vivo
In MDA-MB-231 xenograft tumor tissues, SM-164 causes strong apoptosis and rapid cIAP-1 degradation in addition to tumor regression, but it has no toxic effects on normal mouse tissues.[2]
The combination of SM-164 and TRAIL causes tumor regression without being toxic to animals because SM-164 induces cIAP1 degradation in tumor tissues and significantly increases TRAIL's in vivo antitumor activity. [3]
Enzyme Assay
The FP-based assay for the XIAP BIR3 protein is described. In a nutshell, 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. This fluorescent tracer has a 17.9 nM Kd value to XIAP BIR3. In experiments involving competitive binding, a tested substance 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; 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 for the cIAP-2 BIR3 protein is found to be 6.6 nM. 25 nM of the cIAP-2 BIR3 protein and 2 nM of the SM5F tracer are used in competitive binding experiments. A bivalent fluorescently tagged tracer known as Smac-1F is used in an FP-based competitive binding assay to measure the binding affinities of Smac mimetics to XIAP that contains both BIR2 and BIR3 domains. The bivalent tagged tracer to XIAP containing BIR2 and BIR3 domains has a Kd value of 2.3 nM. In competitive binding tests, a test substance is incubated with 3 nM of XIAP protein containing both BIR2 and BIR3 domains (residues 120–356) and 1 nM of in the same assay buffer.
Cell Assay
SM-164 (1 μM) was applied to cells that had previously received HG (5 μM) treatment for 30 min.
References

[1]. J Am Chem Soc . 2007 Dec 12;129(49):15279-94.

[2]. Cancer Res . 2008 Nov 15;68(22):9384-93.

[3]. Mol Cancer Ther . 2011 May;10(5):902-14.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C62H84N14O6
Molecular Weight
1121.45
Exact Mass
1120.66983
Elemental Analysis
C, 66.40; H, 7.55; N, 17.49; O, 8.56
CAS #
957135-43-2
Appearance
Solid powder
SMILES
C[C@@H](C(=O)N[C@H]1CCCC[C@H]2CC[C@H](N2C1=O)C(=O)N[C@@H](C3=CC=CC=C3)C4=CN(N=N4)CCCCC5=CC=C(C=C5)CCCCN6C=C(N=N6)[C@H](C7=CC=CC=C7)NC(=O)[C@@H]8CC[C@H]9N8C(=O)[C@H](CCCC9)NC(=O)[C@H](C)NC)NC
InChi Key
LGYDZXNSSLRFJS-IOQQVAQYSA-N
InChi Code
InChI=1S/C62H84N14O6/c1-41(63-3)57(77)65-49-27-13-11-25-47-33-35-53(75(47)61(49)81)59(79)67-55(45-21-7-5-8-22-45)51-39-73(71-69-51)37-17-15-19-43-29-31-44(32-30-43)20-16-18-38-74-40-52(70-72-74)56(46-23-9-6-10-24-46)68-60(80)54-36-34-48-26-12-14-28-50(62(82)76(48)54)66-58(78)42(2)64-4/h5-10,21-24,29-32,39-42,47-50,53-56,63-64H,11-20,25-28,33-38H2,1-4H3,(H,65,77)(H,66,78)(H,67,79)(H,68,80)/t41-,42-,47-,48-,49-,50-,53-,54-,55-,56-/m0/s1
Chemical Name
(3S,6S,10aS)-N-[(S)-[1-[4-[4-[4-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]butyl]phenyl]butyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide
Synonyms
SM 164; SM-164; SM164
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 3~25 mg/mL (2.7~22.3 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 0.8917 mL 4.4585 mL 8.9170 mL
5 mM 0.1783 mL 0.8917 mL 1.7834 mL
10 mM 0.0892 mL 0.4459 mL 0.8917 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Biological Data
  • SM-164 induces rapid cIAP-1 degradation and robust apoptosis in tumor tissues and achieves tumor regression, but causes minimal toxicity to mouse tissues. Cancer Res . 2008 Nov 15;68(22):9384-93.
  • SM-164 potentiates cell viability inhibition by TRAIL in both TRAIL-sensitive and TRAIL-resistant cancer cell lines of three tumor types. Mol Cancer Ther . 2011 May;10(5):902-14.
  • SM-164 enhances TRAIL-induced apoptosis through amplification of caspase-8 mediated apoptotic signals. Mol Cancer Ther . 2011 May;10(5):902-14.
  • SM-164 enhances TRAIL-induced anticancer activity by targeting cIAP1 and XIAP, but not by targeting cIAP2. Mol Cancer Ther . 2011 May;10(5):902-14.
  • RIP1 plays an essential role in TRAIL-sensitization by SM-164 but not in the single-agent activity of TRAIL. Mol Cancer Ther . 2011 May;10(5):902-14.
  • SM-164 induces cIAP1 degradation in tumor tissues and dramatically enhances the in vivo antitumor activity of TRAIL and the combination of SM-164 and TRAIL achieves tumor regression without toxicity to animals. Mol Cancer Ther . 2011 May;10(5):902-14.
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