KH-176 (Sonlicromanol) is a novel, potent small molecule ROS-redox modulator with the potential for the treatment of mitochondrial diseases. KH-176 targets the reactive oxygen species which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. KH-176 effectively reduces increased cellular ROS levels and protects OXPHOS deficient primary cells against redox perturbation by targeting the Thioredoxin/Peroxiredoxin system.

Physicochemical Properties

Molecular Formula	C19H28N2O3
Molecular Weight	332.437225341797
Exact Mass	332.209
CAS #	1541170-75-5
Related CAS #	Sonlicromanol hydrochloride;2162149-24-6
PubChem CID	72710875
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	570.8±50.0 °C at 760 mmHg
Flash Point	299.0±30.1 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.583
LogP	2.39
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	24
Complexity	472
Defined Atom Stereocenter Count	2
SMILES	CC1=C(C2=C(CC[C@@](O2)(C)C(=O)N[C@@H]3CCCNC3)C(=C1O)C)C
InChi Key	LZYWLEPSQNXESC-KUHUBIRLSA-N
InChi Code	InChI=1S/C19H28N2O3/c1-11-12(2)17-15(13(3)16(11)22)7-8-19(4,24-17)18(23)21-14-6-5-9-20-10-14/h14,20,22H,5-10H2,1-4H3,(H,21,23)/t14-,19+/m1/s1
Chemical Name	(S)-6-hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidin-3-yl)chromane-2-carboxamide
Synonyms	Sonlicromanol KH-176 KH 176 KH176
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

ln Vivo	The pharmacotherapy of mitochondrial illnesses linked with CI deficiency may benefit from the use of sonlicromanol (KH176, 10 mg/kg, intraperitoneally, twice daily), as long as it is used independently and without additive effects [3].
Animal Protocol	Animal/Disease Models: Ndufs4−/− mice [3]. Doses: 10 mg/kg. Route of Administration: intraperitoneal (ip) injection twice (two times) daily. Experimental Results: Ndufs4−/− mice experienced increased lifespan, similar to KH176 and clofibrate monotherapy.
References	[1]. X Jiang, et al. Mechanism of action and potential applications of selective inhibition of microsomal prostaglandin E synthase-1-mediated PGE 2 biosynthesis by sonlicromanol's metabolite KH176m. Sci Rep. 2021 Jan 13;11(1):880. [2]. Zikai Feng, et al. Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones. Pharmaceuticals (Basel). 2020 Aug 7;13(8):184. [3]. Sanne J C M Frambach, et al. Effects of clofibrate and KH176 on life span and motor function in mitochondrial complex I-deficient mice. Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165727.
Additional Infomation	Sonlicromanol is under investigation in clinical trial NCT04165239 (The KHENERGYZE Study).

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.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0081 mL	15.0403 mL	30.0806 mL
	5 mM	0.6016 mL	3.0081 mL	6.0161 mL
	10 mM	0.3008 mL	1.5040 mL	3.0081 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.