| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Sonlicromanol targets reactive oxygen species (ROS), which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. The active parent compound and its in vivo active metabolite, KH176m, act as potent ROS-redox modulators. KH176m also selectively inhibits LPS or IL-1β-induced microsomal prostaglandin E synthase-1 (mPGES-1) expression.
|
|---|---|
| ln Vitro |
In vitro, sonlicromanol effectively reduces increased cellular ROS levels and protects OXPHOS-deficient primary cells against redox perturbation. Its active metabolite KH176m inhibits mPGES-1-mediated PGE2 biosynthesis and inhibits ferroptosis.
|
| ln Vivo |
Ndufs4−/− mice's brains retain microstructural coherence when sonlicromanol (KH176) hydrochloride is administered[1].
In vivo, sonlicromanol is being evaluated in clinical trials for mitochondrial diseases, including the mitochondrial DNA 3243A>G variant. It has also been studied for reducing fatigue in patients with long COVID. The compound is currently in phase IIb development. |
| Enzyme Assay |
Cell-free assays for sonlicromanol are not well defined, as its mechanism is based on cellular redox modulation. The compound's ability to scavenge ROS can be measured in cell-free systems using chemical ROS generators and fluorescent probes.
|
| Cell Assay |
In vitro cellular assays involve treating OXPHOS-deficient cells with sonlicromanol and measuring ROS levels using fluorescent probes, such as DCFH-DA. Cell viability and protection against redox perturbation are also assessed.
|
| Animal Protocol |
Animal/Disease Models: Ndufs4−/− mice (Leigh Disease model)[1].
Doses: 10 mg/kg. Route of Administration: IP, daily (PD14-PD45, 32 days). Experimental Results: Dramatically improve rotarod and gait performance and decreased the degeneration of retinal ganglion cells. Resulted in statistically Dramatically higher FA values in the external capsule and a similar trend was found in the cerebral peduncle. In vivo animal studies for sonlicromanol have been conducted in models of mitochondrial disease. The compound is administered orally, and its effects on mitochondrial function, ROS levels, and disease symptoms are measured. |
| ADME/Pharmacokinetics |
Sonlicromanol is orally bioavailable. It is metabolized to an active metabolite, KH176m, which contributes to its pharmacological effects. The compound is being studied in clinical trials, and its pharmacokinetic properties are being characterized.
|
| Toxicity/Toxicokinetics |
Sonlicromanol is generally well-tolerated in clinical trials. Common adverse effects are not well documented but are expected to be manageable. The compound's safety profile is being evaluated in ongoing studies.
|
| References | |
| Additional Infomation |
Sonlicromanol (KH176) is an investigational drug being developed by Khondrion for the treatment of mitochondrial diseases. It is currently in phase IIb clinical development. The compound has also been studied for long COVID-related fatigue. Its mechanism involves ROS-redox modulation and inhibition of mPGES-1.
|
| Molecular Formula |
C19H29CLN2O3
|
|---|---|
| Molecular Weight |
368.898164510727
|
| Exact Mass |
368.186
|
| CAS # |
2162149-24-6
|
| Related CAS # |
Sonlicromanol;1541170-75-5
|
| PubChem CID |
72710874
|
| Appearance |
White to yellow solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
25
|
| Complexity |
472
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
Cl.O1C2C(C)=C(C)C(=C(C)C=2CC[C@@]1(C)C(N[C@H]1CNCCC1)=O)O
|
| InChi Key |
HVFWCHDZDIRYBZ-MQZJHDQISA-N
|
| InChi Code |
InChI=1S/C19H28N2O3.ClH/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);1H/t14-,19+;/m1./s1
|
| Chemical Name |
(2S)-6-hydroxy-2,5,7,8-tetramethyl-N-[(3R)-piperidin-3-yl]-3,4-dihydrochromene-2-carboxamide;hydrochloride
|
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 170 mg/mL (460.83 mM)
H2O: ≥ 100 mg/mL (271.08 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.55 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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 4.25 mg/mL (11.52 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 42.5 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. View More
Solubility in Formulation 3: ≥ 4.25 mg/mL (11.52 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7108 mL | 13.5538 mL | 27.1076 mL | |
| 5 mM | 0.5422 mL | 2.7108 mL | 5.4215 mL | |
| 10 mM | 0.2711 mL | 1.3554 mL | 2.7108 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.
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
