M109S is a novel small molecule that protects cells from mitochondria-dependent apoptosis both in vitro and in vivo. M109S may be used to become a research tool to study the mechanisms of cell death and develop treatments targeting mitochondria-dependent cell death pathways. M109S has good brain permeability.

Physicochemical Properties

CAS #	2578300-07-7
Appearance	White to off-white 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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	caspase-3 23.4 nM (EC50) Caspase 3 23.4 nM (EC50)
ln Vitro	M109S (0.1-10000 nM, 24-48 h) prevents apoptosis mediated by Bak and Bax [1]. Staurosporine (HY-15141 STS)-induced apoptosis in MEF cells is inhibited by M109S (0-10 μM, 4 h). In Neuro2a cells, Etoposide (HY-13629)-induced apoptosis is inhibited by M109S (0-10μM, 24 h) [1]. M109S (500 nM, 24 h) prevents the apoptosis that Obatoclax (HY-10969A) causes in ARPE19 cells [1]. Bax's conformational shift (N-terminal exposure) and mitochondrial translocation are inhibited by M109S (500 nM, 48 h) [1]. M109S (1.0 μM, 4 h) decreases reactive oxygen species and mitochondrial oxygen consumption, but M109S (0.1–1 nM, 4 h) boosts glycolysis[1].
ln Vivo	M109S (10 mg/kg, gavaged three times in a 48-hour period) guards against intense light-induced photoreceptor loss in the retina [1]. Orally administered bioactive cell death agent M109S can be injected intraperitoneally at a dose of 1 mg/kg, intravenous at a dose of 5 mg/kg, orally at a dose of 10 mg/kg. It has the ability to cross the blood-brain/retina barrier. inhibitors [1].
Cell Assay	Apoptosis Analysis[1] Cell Types: MEF(Wt, Bax only, Bak only) Tested Concentrations: 0.1 nM, 1 nM, 10 nM, 100 nM, 10000 nM Incubation Duration: 24 h((WT and Bax-only), 48 h (Bak-only) Experimental Results: demonstrated a dose-dependent suppression of caspase activation in all three types of MEFs. Apoptosis Analysis [1] Cell Types: MEF Tested Concentrations: 0 nM, 1.6 nM, 8 nM, 40 nM, 200 nM, 10000 nM Incubation Duration: 4 h Experimental Results: Suppressed STS-induced caspase activation in a dose-dependent manner. Apoptosis Analysis[1] Cell Types: Neuro2a Tested Concentrations: 0 nM, 40 nM, 200 nM, 10000 nM Incubation Duration: 24 h Experimental Results: Suppressed Etoposide-induced caspase activation in a dose-dependent manner. Western Blot Analysis[1] Cell Types: ARPE19 Tested Concentrations: 500 nM Incubation Duration: 24 h Experimental Results: Dramatically inhibited Obatoclax-induced apoptosis in ARPE19 cells comparing to control. Western Blot Analysis[1] Cell Types: iBax cells Tested Concentrations: 500 nM Incubation Duration: 48 h Experimental Results: Dramatically suppressed the amount of immunoprecipitated Bax w
Animal Protocol	Animal/Disease Models: Abca4-/-Rdh8-/- mice Doses: 10 mg/kg Route of Administration: po (oral gavage) Experimental Results: Comparing to mice with M109S, the number of AF spots was similar to that detected in the dark-adapted mice. Animal/Disease Models: Mice and Rat Doses: intraperitoneal (ip)injection (ip, 1 mg/kg), intravenous (iv)injection (iv, 5 mg/kg), or po (oral gavage) (po, 10 mg/kg) Route of Administration: intraperitoneal (ip)injection, intravenous (iv)injection, or po (oral gavage). Experimental Results: demonstrated plasma concentration reached 1.0 mg/mL (2.6 mM) within 30 min from po in mice , and it remained at 596± 134 ng/mL (1.6±0.36 mM) after 24 h, the same as in rat. Plasmic M109S was 565.3±188.3 nM in rats, and 171.0±52.0 nM in retina, 222.7±74.7 nM in brain, respectively.
References	[1]. Development of novel cytoprotective small compounds inhibiting mitochondria-dependent cell death. Science 26, 107916, October 20, 2023.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)