SM-164 structure
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Common Name | SM-164 | ||
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CAS Number | 957135-43-2 | Molecular Weight | 1121.42000 | |
Density | N/A | Boiling Point | N/A | |
Molecular Formula | C62H84N14O6 | Melting Point | N/A | |
MSDS | N/A | Flash Point | N/A |
Use of SM-164SM-164 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. |
Name | sm 164 |
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Synonym | More Synonyms |
Description | SM-164 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. |
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Related Catalog | |
Target |
XIAP:1.39 nM (IC50) cIAP-1:0.31 nM (Ki) XIAP:0.56 nM (Ki) cIAP-2:1.1 nM (Ki) cIAP |
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]. |
Kinase Assay | 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]. |
Cell Assay | 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]. |
Animal Admin | 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]. |
References |
Molecular Formula | C62H84N14O6 |
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Molecular Weight | 1121.42000 |
Exact Mass | 1120.67000 |
PSA | 242.50000 |
LogP | 7.60040 |
Storage condition | 2-8℃ |
SM59 |
(S,3S,3'S,6S,6'S,10aS,10a'S)-N,N'-((1S,1'S)-(1,1'-(4,4'-(1,4-phenylene)bis(butane-4,1-diyl))bis(1H-1,2,3-triazole-4,1-diyl))bis(phenylmethylene))bis(6-((S)-2-(2-methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide) |
(3S,3'S,6S,6'S,10aS,10a'S)-N,N'-((1S,1'S)-((1,4-phenylenebis(butane-4,1-diyl))bis(1H-1,2,3-triazole-1,4-diyl))bis(phenylmethylene))bis(6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide) |
SM-164 |