SM-102 是一种可电离的氨基脂质，可用于形成脂质纳米颗粒 (LNP)。
货号:ajcx23940
CAS:2089251-47-6
分子式:C44H87NO5
分子量：710.2
溶解度:Ethanol : ≥ 100 mg/mL (140.81 mM) DMSO ;100 mg/mL (140.81 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

SM-102 is a synthetic ionizable amino lipid that has been widely used to combine with other lipids to form lipid nanoparticles^[1,2]. Administration of luciferase mRNA in SM-102-containing lipid nanoparticles can induce hepatic luciferase expression in mice^[3]. The formulation containing sm-102 has been significantly used to develop lipid nanoparticles for delivery of mRNA based vaccines^[4.5], as this efficient transfection method based on compressed lipopolysamine coated plasmids has been developed^[6].

SM-102 addition was effective at blocking IK(erg) in a concentration-dependent fashion with a half-maximal concentration (IC₅₀) of 108 μM, a value which is similar to the KD value (i.e., 134 μM) required for its accentuation of deactivation time constant of the current. The hysteretic strength of IK(erg) in response to the long-lasting isosceles-triangular ramp pulse was effectively decreased in the presence of SM-102.

SM-102 (100 μM) diminished the current magnitude further. In MA-10 Leydig cells, the IK(erg) was also blocked by the presence of SM-102. The IC₅₀value for SM-102-induced inhibition of IK(erg) in MA-10 cells was 98 μM^[7]. In BV2 microglial cells, the amplitude of the inwardly rectifying K+ current was inhibited by SM-102. The presence of SM-102 concentration-dependently inhibited IK(erg) in endocrine cells (e.g., GH3 or MA-10 cells).

SM-102 has been implicated in the development of myocarditis following covid-19 vaccination^[8,9]. However, the need remains unmet whether sm-102 exerts any perturbation on the magnitude of transmembrane ionic currents. Since the sizes of IK (IR) and IK (ERG) are widely expressed in cardiac cells^[10], the inhibitory effect of sm-102 in altering IK (IR) and / or IK (ERG) may potentially participate in the functional activity of cardiac function. These polycationic molecules enter the KIR or kerg channel pore from the intracellular side and block the movement of K + ions through the channel at depolarized potentials, thereby ensuring a longer plateau phase of the cardiac action potential^[11]. However, to what extent SM-102-mediated perturbations of membrane ionic currents confer their effectiveness against adverse effects of mRNA based vaccines remains to be further delineated.

参考文献:
[1].Sabnis S, Kumarasinghe E S, Salerno T, et al. A novel amino lipid series for mRNA delivery: improved endosomal escape and sustained pharmacology and safety in non-human primates[J]. Molecular Therapy, 2018, 26(6): 1509-1519.
[2].Hassett K J, Benenato K E, Jacquinet E, et al. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines[J]. Molecular Therapy-Nucleic Acids, 2019, 15: 1-11.
[3].Tao W, Davide J P, Cai M, et al. Noninvasive Imaging of Lipid Nanoparticle-Mediated Systemic [4].Delivery of Small-Interfering RNA to the Liver[J]. Molecular Therapy, 2010, 18(9): 1657-1666.
[4]Reichmuth A M, Oberli M A, Jaklenec A, et al. mRNA vaccine delivery using lipid nanoparticles[J]. Therapeutic delivery, 2016, 7(5): 319-334.
[5]Tenchov R, Bird R, Curtze A E, et al. Lipid Nanoparticles─ From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement[J]. ACS nano, 2021, 15(11): 16982-17015.
[6]Behr J P, Demeneix B, Loeffler J P, et al. Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA[J]. Proceedings of the National Academy of Sciences, 1989, 86(18): 6982-6986.
[7].Cho H Y, Chuang T H, Wu S N. Effective Perturbations on the Amplitude and Hysteresis of Erg-Mediated Potassium Current Caused by 1-Octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6 (undecyloxy) hexyl] amino]-octanoate (SM-102), a Cationic Lipid[J]. Biomedicines, 2021, 9(10): 1367.
[8]Vidula M K, Ambrose M, Glassberg H, et al. Myocarditis and other cardiovascular complications of the mRNA-based COVID-19 vaccines[J]. Cureus, 2021, 13(6).
[9]Williams C B, Choi J, Hosseini F, et al. Acute myocarditis following mRNA-1273 SARS-CoV-2 vaccination[J]. CJC open, 2021, 3(11): 1410-1412.
[10]Martinson A S, Van Rossum D B, Diatta F H, et al. Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr[J]. Proceedings of the National Academy of Sciences, 2014, 111(15): 5712-5717.
[11]Sung R J, Wu S N, Wu J S, et al. Electrophysiological mechanisms of ventricular arrhythmias in relation to Andersen-Tawil syndrome under conditions of reduced I K1: a simulation study[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2006, 291(6): H2597-H2605.

Protocol:

Cell experiment [1]:
Cell lines	GH3 pituitary tumor cells
Preparation Method	The electrophysiological measurements and whole cell current recording tests were performed 5 or 6 days after cells were subcultured (60-80% confluence). GH3 cells were exposed to SM-102 at concentrations of 100 or 300μM.
Reaction Conditions	100μM /300μM 1min
Applications	The peak or sustained component of the inactivating IK (ERG) evoked by a long hyperpolarizing pulses -10 to -90 mV gradually decreased 1 min after GH3 cells were exposed to SM-102 at concentrations of 100 or 300μM. As the rectangular voltage step from -10 to -90 mV with a duration of 1 s was delivered to the examined cell to activate IK(erg), the application of 300 μM SM-102 was noticed to result in a conceivable reduction in the peak or sustained amplitude of IK(erg) to 119 ± 34 or 22 ± 4 pA from control values of 174 ± 43 or 46 ± 7 pA respectively. After a washout of SM-102, the initial IK(erg) was reversed to 169 ± 39 pA. The application of 100 μM SM-102 to cells led to a reduction in IK(erg) amplitude during the upsloping or downsloping limb of the triangular ramp pulse by about 18% or 28%, respectively. The IC50 value required for the SM-102-mediated inhibition of IK(erg) observed in MA-10 cells was estimated to be 98 μM.
参考文献: [1]. Cho H Y, Chuang T H, Wu S N. Effective Perturbations on the Amplitude and Hysteresis of Erg-Mediated Potassium Current Caused by 1-Octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6 (undecyloxy) hexyl] amino]-octanoate (SM-102), a Cationic Lipid[J]. Biomedicines, 2021, 9(10): 1367.