CMS-121 (CMS121) is a novel and potent fisetin-based quinolone derivative acting as an orally active acetyl-CoA carboxylase 1 (ACC1) inhibitor with anti-aging, neuroprotective, anti-inflammatory, antioxidative, and renoprotective activities. It is currently in the animal toxicology studies required for FDA approval to start clinical trials for AD treatment.

Physicochemical Properties

Molecular Formula	C20H19NO3
Molecular Weight	321.369765520096
Exact Mass	321.136
CAS #	1353224-53-9
PubChem CID	135741221
Appearance	Light yellow to yellow solid powder
LogP	4.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	24
Complexity	412
Defined Atom Stereocenter Count	0
SMILES	O(C1C=C(C2C=CC(=C(C=2)O)O)N=C2C=CC=CC=12)C1CCCC1
InChi Key	OMHNVUCFPJJLKD-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H19NO3/c22-18-10-9-13(11-19(18)23)17-12-20(24-14-5-1-2-6-14)15-7-3-4-8-16(15)21-17/h3-4,7-12,14,22-23H,1-2,5-6H2
Chemical Name	4-(4-(cyclopentyloxy)quinolin-2-yl)benzene-1,2-diol
Synonyms	CMS-121, CMS 121, CMS121
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	Acetyl-CoA carboxylase 1 (ACC1)[1]
ln Vitro	ACC1 is phosphorylated at serine 79 more when treated with CMS-121 (1 µM; 4 hours; HT22 cells). Elevating acetyl-CoA in cells is possible with CMS-121 [1].
ln Vivo	When given to rapidly aging SAMP8 mice, CMS-121 (~20 mg/kg; oral dose; daily; for 4 months; female SAMP8 mice) lowers both cognitive decline and metabolic and transcriptional indicators of aging in the brain. Through controlling the metabolism of acetyl-coenzyme A (acetyl-CoA), CMS-121 maintains mitochondrial homeostasis[1].
Cell Assay	Western Blot Analysis[1] Cell Types: HT22 cells Tested Concentrations: 1 µM Incubation Duration: 4 hrs (hours) Experimental Results: Increases the phosphorylation of ACC1 at serine 79.
Animal Protocol	Animal/Disease Models: Female SAMP8 mice (9 months old)[1] Doses: ~20 mg/kg/day Route of Administration: Oral administration; daily; for 4 months Experimental Results: decreased cognitive decline as well as metabolic and transcriptional markers of aging in the brain.
References	[1]. Elevating acetyl-CoA levels reduces aspects of brain aging. Elife. 2019 Nov 19;8. pii: e47866. [2]. Chemical modification of the multitarget neuroprotective compound fisetin. J Med Chem. 2012 Jan 12;55(1):378-89. [3]. Back to the future with phenotypic screening. ACS Chem Neurosci. 2014 Jul 16;5(7):503-13.
Additional Infomation	CMS-121 is a quinolone derivative and an orally active acetyl-CoA carboxylase 1 (ACC1) inhibitor. CMS-121 protects HT22 cells against ischemia and oxidative damage. CMS-121 has strong neuroprotective, anti-inflammatory, antioxidative and renoprotective activities.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~155.58 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.47 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 20.8 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: ≥ 2.08 mg/mL (6.47 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 20.8 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1117 mL	15.5584 mL	31.1168 mL
	5 mM	0.6223 mL	3.1117 mL	6.2234 mL
	10 mM	0.3112 mL	1.5558 mL	3.1117 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.