Cat. No.: HY-171705

KMS99220

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Based on 1 Customer Validation

KMS99220 is an orally active, blood-brain barrier-permeable activator of the Nrf2 inhibitory protein Keap-1. KMS99220 enhances the activity of AMPK, activates the Nrf2 signaling pathway, and reduces the phosphorylation of IκB, nuclear translocation of NFκB, as well as the phosphorylation levels of JNK, IKK and p38 MAPK via HO-1. KMS99220 binds to Keap1 to trigger the nuclear translocation of Nrf2, induces the expression of HO-1, NQO1, GCLC, GCLM and proteasome subunits; enhances proteasomal enzymatic activity; inhibits iNOS expression, nitric oxide production and IL-1β generation; attenuates microglial activation; reduces α-synuclein aggregation; and prevents dopaminergic neuron degeneration and motor dysfunction. KMS99220 prevents the degeneration of dopaminergic neurons in the substantia nigra, induces the expression of Nrf2 downstream target genes, and effectively ameliorates associated motor dysfunction in a mouse model of Parkinson's disease. KMS99220 is applicable to research related to Parkinson's disease.

For research use only. We do not sell to patients.

Purity: 99.48%
CAS No.: 1478585-60-2
Formula: C₂₃H₂₅ClF₃NO₃
Molecular Weight:455.90

Storage:

4°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

KMS99220 Chemical Structure

CAS No.: 1478585-60-2

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

All AMPK Isoforms :

All JNK Isoforms :

All IKK Isoforms :

All p38 MAPK Isoforms :

All NO Synthase Isoforms :

All α-synuclein Isoforms :

All Interleukin Related Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
U2OS	EC₅₀	1.36 μM Compound: 6a	Activation of NRF2 in human U2OS cells co-expressing Keap1 (unknown origin) assessed as induction of NRF2 translocation to nucleus incubated for 6 hrs by beta-galactosidase based chemiluminescent assay Activation of NRF2 in human U2OS cells co-expressing Keap1 (unknown origin) assessed as induction of NRF2 translocation to nucleus incubated for 6 hrs by beta-galactosidase based chemiluminescent assay	[PMID: 31670201]

In Vitro

KMS99220 (5-10 μM; 40 min) directly activates purified AMPK protein, increasing its enzymatic activity by 17% at a concentration of 10 μM^[1].
KMS99220 (1-10 μM; 15 min) dose-dependently enhances the phosphorylation level of AMPK in BV2 cells^[1].
KMS99220 (6-24 h, 0.5-10 μM) dose-dependently induces HO-1 mRNA and protein expression in BV2 mouse microglia^[1].
KMS99220 (10 μM; 1 h) inhibits LPS (HY-D1056)-induced nuclear translocation of NF-κB (p65), suppresses IκB phosphorylation, and maintains the total IκB protein level in BV2 mouse microglial cells^[1].
KMS99220 (6 h for iNOS mRNA detection, 24 h for iNOS protein and nitrite detection; 0.5-10 μM) inhibits LPS-induced iNOS expression and nitric oxide production in BV2 mouse microglia in a dose-dependent manner, and completely suppresses NO production at a concentration of 10 μM^[1].
KMS99220 (pre-incubated at 10 μM for 1 h) exerts Nrf2-independent early anti-inflammatory effects in BV2 mouse microglia, including induction of HO-1 expression in Nrf2-knockdown cells, inhibition of LPS-induced IκB phosphorylation, and suppression of LPS-induced iNOS expression^[1].
KMS99220 (5-100 μM) binds to purified Keap1 protein with high affinity, with a K_d value of 2.2 × 10^-8 M^[2].
KMS99220 (3-24 h, 0.5-3 μM) promotes nuclear translocation of Nrf2 (reaching 2.6-fold after treatment with 3 μM for 3 h) and total Nrf2 expression (reaching 1.9-fold after treatment with 3 μM for 24 h) in CATH.a dopaminergic cells without inducing cytotoxicity^[2].
KMS99220 (0.5-3 μM; 6 h-24 h) dose-dependently induces the mRNA and protein expression of Nrf2-dependent antioxidant enzymes (NQO1, HO-1, GCLC, GCLM) in CATH.a dopaminergic cells, with the effect peaking at 3 μM^[2].
KMS99220 (0.5-3 μM; 16-24 h) dose-dependently upregulates the mRNA and protein expression levels of proteasome subunits (PSMB5, PSMB8, PSMA1, PSMB7) in CATH.a dopaminergic cells, and enhances their chymotrypsin-like, trypsin-like and caspase-like proteasome activities, with the peak effect observed at 3 μM^[2].
KMS99220 (24 h, 3 μM) reduces the level of aggregated α-synuclein in CATH.a dopaminergic cells transfected with GFP-α-syn A53T^[2].
KMS99220 (0.5-10 μM; 6-24 h) inhibits LPS-induced production of IL-1β mRNA and protein in BV-2 microglia^[3].
KMS99220 (1.5 h, 0.5-10 μM) inhibits LPS-induced phosphorylation of IKK, JNK, p38 MAPK and ERK in BV-2 microglia via HO-1 mediation, with the strongest inhibitory effect observed at the concentration of 10 μM^[3].
KMS99220 (0.5-10 μM; 3-24 h) activates the Nrf2 pathway in BV-2 microglial cells with or without LPS stimulation by promoting the nuclear translocation of Nrf2, and induces the expression of Nrf2 target genes (HO-1, NQO1, GCLC, GCLM) and their corresponding proteins in a dose-dependent manner^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

BV2 cells
Concentration:

0, 1, 5, 10 μM (15 min incubation); 10 μM (15, 30, 60, 180 min incubation)
Incubation Time:

15 min (dose-dependent analysis); 15, 30, 60, 180 min (time-course analysis)
Result:

Induced p-AMPK levels in a dose-dependent manner: 2.6-fold at 1 μM, 3.4-fold at 5 μM, 5.1-fold at 10 μM relative to untreated control after 15 min incubation.
Reached peak p-AMPK levels of 2.3-fold relative to control at 15 min with 10 μM treatment, then decreased over time.
Caused nuclear accumulation of p-AMPK between 15 and 60 min with 10 μM treatment.

RT-PCR^[1]

Cell Line:

BV2 cells
Concentration:

0, 0.5, 1, 5, 10 μM
Incubation Time:

6 h
Result:

Dramatically and dose-dependently elevated the mRNA
levels of HO-1.

Western Blot Analysis^[1]

Cell Line:

LPS-challenged BV2 mouse microglial cells
Concentration:

10 μM (pre-incubation)
Incubation Time:

1 h pre-incubation prior to 1 h LPS challenge
Result:

Reduced LPS-induced nuclear NFκB (p65) levels to 0.5-fold relative to LPS-treated control.

Western Blot Analysis^[1]

Cell Line:

LPS-challenged BV2 mouse microglial cells
Concentration:

10 μM (pre-incubation)
Incubation Time:

1 h pre-incubation prior to 0.5 h LPS challenge
Result:

Reduced LPS-induced p-IκB levels to 0.7-fold relative to LPS-treated control.
Prevented the LPS-induced decrease in total IκB protein levels, maintaining IκB at 2.5-fold relative to LPS-treated control.

Parmacokinetics

Species	Dose	Route	C_max	AUC_all	F	CL	V_z	T_1/2
Mice^[2]	5 mg/kg	i.v.	/	165.3 ng·h	/	30.2 L/h/kg	58.9 L/kg	1.4 h
Mice^[2]	30 mg/kg	p.o.	224.4 ng/mL	718.7 ng·h	72.5 %	/	/	/

In Vivo

KMS99220 (10-30 mg/kg; p.o.; once every 24 hours; for 3 consecutive days) prevents MPTP (HY-15608)-induced nigrostriatal dopaminergic neuron degeneration, activates Nrf2 target genes, completely reverses associated motor deficits in male C57BL/6 mice, fully abrogates MPTP-induced microglial activation in mice, reduces iNOS levels, and normalizes IL-1β levels^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6 (male, 23-25 g, MPTP-induced Parkinson's disease model)^[2]
Dosage:

10 mg/kg; 30 mg/kg
Administration:

p.o.; every 24 h; 3 consecutive days
Result:

Attenuated loss of tyrosine hydroxylase (TH)-immunopositive nigral dopaminergic neurons to 78% of vehicle-treated control at 10 mg/kg.
Attenuated loss of TH-immunopositive striatal fibers to 76% of vehicle-treated control at 10 mg/kg.
Reversed MPTP-induced hindlimb movement deficits at 10 mg/kg.
Restored rotarod latency to 289 seconds at 10 mg/kg.
Normalized vertical grid test parameters to near vehicle-control levels at 10 mg/kg.
Attenuated loss of TH-immunopositive nigral dopaminergic neurons to 84% of vehicle-treated control at 30 mg/kg.
Fully preserved TH-immunopositive striatal fibers to 98% of vehicle-treated control at 30 mg/kg.
Reversed MPTP-induced hindlimb movement deficits at 30 mg/kg.
Restored rotarod latency to 292 seconds at 30 mg/kg.
Normalized vertical grid test parameters to near vehicle-control levels at 30 mg/kg.
Increased striatal protein levels of Nrf2 to 4.0-fold of vehicle-treated control, NQO1 to 1.4-fold, HO-1 to 2.2-fold, GCLM to 4.0-fold, and GCLC to 1.6-fold at 30 mg/kg.
Increased HO-1 (2.3-fold) and GCLM (7.0-fold) staining in surviving TH-positive nigral dopaminergic neurons at 30 mg/kg.
Completely abrogated MPTP-induced increases in Iba-1 immunoreactivity (microglial activation) to levels not significantly different from vehicle-treated controls at both 10 mg/kg and 30 mg/kg doses.
Suppressed MPTP-induced increases in striatal inducible nitric oxide synthase (iNOS) protein levels by 70% at 30 mg/kg dose.
Completely nullified MPTP-induced increases in nigral interleukin 1 beta (IL-1β) levels, returning IL-1β to levels not significantly different from vehicle-treated controls at 30 mg/kg dose.

Chemical Information

CAS No. 1478585-60-2
Appearance Solid
Molecular Weight 455.90
Formula C₂₃H₂₅ClF₃NO₃
Color White to off-white
SMILES

O=C(C1=CC=C(C=C1)OCCCN2CCOCC2)/C=C/C3=C(C=CC=C3)C(F)(F)F.Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (219.35 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.1935 mL

10.9673 mL

21.9346 mL

5 mM

0.4387 mL

2.1935 mL

4.3869 mL

10 mM

0.2193 mL

1.0967 mL

2.1935 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 5 mg/mL (10.97 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 5 mg/mL (10.97 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 5 mg/mL (10.97 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (283 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Lee JA, et al. The Novel Neuroprotective Compound KMS99220 Has an Early Anti-neuroinflammatory Effect via AMPK and HO-1, Independent of Nrf2. Exp Neurobiol. 2018;27(5):408-418. [Content Brief]

[2]. Lee JA, et al. Activation of the Nrf2 signaling pathway and neuroprotection of nigral dopaminergic neurons by a novel synthetic compound KMS99220. Neurochem Int. 2018;112:96-107. [Content Brief]

[3]. Lee JA, et al. KMS99220 Exerts Anti-Inflammatory Effects, Activates the Nrf2 Signaling and Interferes with IKK, JNK and p38 MAPK via HO-1. Mol Cells. 2019;42(10):702-710. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.1935 mL	10.9673 mL	21.9346 mL	54.8366 mL
	5 mM	0.4387 mL	2.1935 mL	4.3869 mL	10.9673 mL
	10 mM	0.2193 mL	1.0967 mL	2.1935 mL	5.4837 mL
	15 mM	0.1462 mL	0.7312 mL	1.4623 mL	3.6558 mL
	20 mM	0.1097 mL	0.5484 mL	1.0967 mL	2.7418 mL
	25 mM	0.0877 mL	0.4387 mL	0.8774 mL	2.1935 mL
	30 mM	0.0731 mL	0.3656 mL	0.7312 mL	1.8279 mL
	40 mM	0.0548 mL	0.2742 mL	0.5484 mL	1.3709 mL
	50 mM	0.0439 mL	0.2193 mL	0.4387 mL	1.0967 mL
	60 mM	0.0366 mL	0.1828 mL	0.3656 mL	0.9139 mL
	80 mM	0.0274 mL	0.1371 mL	0.2742 mL	0.6855 mL
	100 mM	0.0219 mL	0.1097 mL	0.2193 mL	0.5484 mL

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KMS99220

Epigenetics Compound Library

Immunology/Inflammation Compound Library

Kinase Inhibitor Library

MAPK Compound Library

Neuronal Signaling Compound Library

NF-κB Signaling Compound Library

PI3K/Akt/mTOR Compound Library

Stem Cell Signaling Compound Library

CNS-Penetrant Compound Library

Anti-Aging Compound Library

Antioxidant Compound Library

Differentiation Inducing Compound Library

Reprogramming Compound Library

Oxygen Sensing Compound Library

Ferroptosis Compound Library

Glycolysis Compound Library

Pyroptosis Compound Library

Cytoskeleton Compound Library

Orally Active Compound Library

Neuroprotective Compound Library

Anti-Lung Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Anti-Obesity Compound Library

Angiogenesis-Related Compound Library

Transcription Factor-Targeted Library

Lipid Metabolism Compound Library

Glucose Metabolism Compound Library

Anti-Liver Cancer Compound Library

Antidepressant Compound Library

Anti-Prostate Cancer Compound Library

Anti-Pulmonary Fibrosis Compound Library

Pain-Related Compound Library

Mitochondrial Protection Compound Library

Metabolic Enzyme Compound Library

Membrane Protein-targeted Compound Library

Autoimmune Disease Compound Library

Cytokine Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Radioprotector Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Anti-Gastric Cancer Compound Library

Protein Kinase Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

Cell Proliferation Compound Library

Lactic Acid Metabolic Compound Library

High-Throughput Bioactive Compound Library

Anti-Rheumatic Arthritis Compound Library

Lactylation Compound Library

All AMPK Isoforms

All JNK Isoforms

All IKK Isoforms

All p38 MAPK Isoforms

All NO Synthase Isoforms

All α-synuclein Isoforms

All Interleukin Related Isoforms

Biological Activity

Chemical Information

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

KMS99220 Related Classifications

Cat. No.: HY-171705