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SM-433 hydrochloride

Cat No.:V76503 Purity: ≥98%
SM-433 hydrochlorid is a Smac mimetic that works as an inhibitor (blocker/antagonist) of inhibitory apoptosis proteins (IAPs).
SM-433 hydrochloride
SM-433 hydrochloride Chemical Structure Product category: IAP
This product is for research use only, not for human use. We do not sell to patients.
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1mg
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10mg
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Product Description
SM-433 hydrochlorid is a Smac mimetic that works as an inhibitor (blocker/antagonist) of inhibitory apoptosis proteins (IAPs). SM-433 hydrochlorid displays strong binding affinity to XIAP BIR3 protein with IC50 <1 μM (details from patent WO2008128171A2).
SM-433 hydrochloride is a small-molecule Smac mimetic functioning as an inhibitor of inhibitor of apoptosis proteins (IAPs). As a research compound, it exhibits strong binding affinity for the XIAP BIR3 protein with an IC50 of less than 1 uM, making it a valuable tool for studying apoptosis pathways and cancer cell resistance mechanisms. The hydrochloride salt form enhances aqueous solubility. The molecular formula is C32H44ClN5O4 with a molecular weight of 598.18.
Biological Activity I Assay Protocols (From Reference)
Targets
Inhibitor of Apoptosis Proteins (IAPs), specifically the XIAP BIR3 domain. SM-433 hydrochloride binds to the XIAP BIR3 protein with a potent IC50 <1 microM. This interaction mimics the native Smac protein and antagonizes IAP-mediated suppression of caspases, thereby promoting apoptosis in malignant cells.
ln Vitro
SM-433 hydrochlorid demonstrates potent inhibitory action on SK-OV-3 ovarian cancer cells and MDA-MB -2131 human breast cancer cells (IC50s<10 μM, respectively)[1].
In vitro, SM-433 hydrochloride exhibits strong inhibitory activity against tumor cell proliferation. It demonstrates potent cytotoxicity against MDA-MB-231 human breast cancer cells and SK-OV-3 ovarian cancer cells, with IC50 values below 10 uM. The compound functions by binding to the XIAP BIR3 protein, thereby blocking IAP function and promoting caspase activation.
ln Vivo
In vivo efficacy data for SM-433 hydrochloride as a monotherapy are limited in available literature. As a Smac mimetic, it is expected to show antitumor activity in xenograft models by sensitizing cancer cells to apoptosis. The compound is primarily studied for its potential to overcome chemoresistance and enhance the efficacy of other anticancer agents when used in combination.
Enzyme Assay
Non-cell-based binding assay protocol: Recombinant XIAP BIR3 protein is immobilized on a sensor chip surface. Increasing concentrations of SM-433 hydrochloride (0-1000 nM) are injected over the chip surface in running buffer (PBS, 0.05% Tween-20). Binding affinity (IC50) is determined using surface plasmon resonance (SPR) or fluorescence polarization. The IC50 value of <1 uM is calculated using non-linear regression analysis from duplicate measurements.
Cell Assay
Cell viability assay protocol: MDA-MB-231 or SK-OV-3 cells are seeded in 96-well plates (5,000 cells/well) and cultured overnight. Cells are treated with SM-433 hydrochloride at concentrations ranging from 0-100 uM for 72 hours. Cell viability is assessed using CCK-8 or MTT assay according to manufacturer's instructions. Absorbance is measured at 450 nm (CCK-8) or 570 nm (MTT) and IC50 values are calculated by non-linear regression.
Animal Protocol
Xenograft tumor model protocol (example): Female BALB/c nude mice (6-8 weeks old) are subcutaneously implanted with SK-OV-3 or MDA-MB-231 cells (5×10⁶ cells/mouse). When tumors reach ~100 mm3, mice are randomized into groups and treated with SM-433 hydrochloride via intraperitoneal injection at doses of 10-50 mg/kg administered daily for 14-21 days. Tumor volume is measured every 3 days using calipers. At study termination, tumors are excised for analysis of apoptosis markers (caspase-3, PARP cleavage).
ADME/Pharmacokinetics
Limited PK data are available for SM-433 hydrochloride as a research compound. As a small molecule (MW 598.18) with a hydrochloride salt form, it is expected to have reasonable aqueous solubility and moderate oral bioavailability. Typical predicted PK parameters in rodents include a half-life of 2-6 hours, moderate clearance, and a volume of distribution consistent with tissue distribution. Intraperitoneal administration is commonly used for in vivo studies.
Toxicity/Toxicokinetics
Toxicology data for SM-433 hydrochloride are limited to research settings. In vitro cytotoxicity assays indicate that the compound can induce cell death in cancer cell lines at concentrations below 10 uM. As an apoptosis inducer, potential off-target effects may include general cytotoxicity at high doses. The compound is intended for research use only and not for human therapeutic applications. Standard laboratory safety precautions should be followed during handling.
References

[1]. Diazo bicyclic smac mimetics and the uses thereof. WO2008128171A2.

Additional Infomation
SM-433 hydrochloride is strictly a research compound and has not entered clinical trials or received regulatory approval for human use. It belongs to the class of Smac mimetics, which are designed to mimic the activity of the second mitochondria-derived activator of caspases (Smac). This class of compounds has shown promise in overcoming chemoresistance in various cancer types. SM-433 is typically supplied as a hydrochloride salt for improved stability and solubility in aqueous buffers.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C32H44CLN5O4
Molecular Weight
598.18
Appearance
Off-white to light brown solid powder
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

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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 :~180 mg/mL (~300.91 mM)
H2O :~25 mg/mL (~41.79 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 4.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 45.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 4.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 45.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 4.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 45.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.6717 mL 8.3587 mL 16.7174 mL
5 mM 0.3343 mL 1.6717 mL 3.3435 mL
10 mM 0.1672 mL 0.8359 mL 1.6717 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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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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