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Chemical Structure| 217094-32-1 Chemical Structure| 217094-32-1

Structure of K-604 2HCl
CAS No.: 217094-32-1

Chemical Structure| 217094-32-1

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K-604 is a potent and selective acyl-CoA:cholesterol acyltransferase 1 (ACAT-1) inhibitor. K-604 inhibits against acyl-coenzyme A (acyl-CoA):cholesterol O-acyltransferase-1 (ACAT1, SOAT1) activitiy in a selective (IC50 = 450 nM vs. 102.85 μ M against human ACAT1 and ACAT2, respectively) and acyl-CoA-competitive (Ki = 378 nM against oleoyl-coA) manner.

Synonyms: K-604 dihydrochloride

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Product Details of K-604 2HCl

CAS No. :217094-32-1
Formula : C23H32Cl2N6OS3
M.W : 575.64
SMILES Code : O=C(NC1=C(SC)C=C(C)N=C1SC)CN2CCN(CCSC3=NC4=CC=CC=C4N3)CC2.[H]Cl.[H]Cl
Synonyms :
K-604 dihydrochloride
MDL No. :MFCD30738203
InChI Key :DEKWEGUBUYKTAV-UHFFFAOYSA-N
Pubchem ID :22272715

Safety of K-604 2HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HMC3 cells 0.5 µM 4 hours Measure ACAT activity and observe cholesterol accumulation around ACAT1/SOAT1 after K-604 treatment Int J Mol Sci. 2023 Mar 14;24(6):5525
CHO cells 0.5 µM 4 hours Measure ACAT activity and observe cholesterol accumulation around ACAT1/SOAT1 after K-604 treatment Int J Mol Sci. 2023 Mar 14;24(6):5525
SHSY5Y cells 0.5 µM 4 hours Measure ACAT activity and observe cholesterol accumulation around ACAT1/SOAT1 after K-604 treatment Int J Mol Sci. 2023 Mar 14;24(6):5525
N9 cells 0.5 µM 4 hours Measure ACAT activity and observe cholesterol accumulation around ACAT1/SOAT1 after K-604 treatment Int J Mol Sci. 2023 Mar 14;24(6):5525
rat brain capillary endothelial cells 1 μM 30 minutes Evaluate the BBB permeability of K-604. Results showed that the apparent permeability coefficient (Papp) of K-604 (21.9 × 10−6 cm/s) was lower than that of carbamazepine (47.8 × 10−6 cm/s). ACS Omega. 2019 Oct 2;4(16):16943-16955
N9 microglial cells 0.5 µM 4 hours K-604 significantly reduced LPS-induced pro-inflammatory gene expressions and increased TLR4 endocytosis, thereby enhancing TLR4 trafficking to lysosomes for degradation. Int J Mol Sci. 2023 Mar 15;24(6):5616
Primary cortical neurons 0.5 µM 24 hours K604 reduced P301L-tau protein levels and increased LC3-II levels, indicating enhanced autophagosome formation. Neurobiol Aging. 2015 Jul;36(7):2248-2259
Mouse neuroblastoma cell line N2a 0.1 to 1 µM 24 hours K604 at 0.1 to 1 µM inhibited ACAT activity by 60-80% and increased the LC3-II/LC3-I ratio, indicating enhanced autophagosome formation. Neurobiol Aging. 2015 Jul;36(7):2248-2259

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
ICR female mice Oral and intranasal administration 6 mg/kg (oral), 32.4 μg/10 μL (intranasal), 108 μg/10 μL (intranasal) Single dose or once daily for 7 days Evaluate the efficiency of K-604 delivery to the brain via intranasal administration. Results showed that the brain AUC after intranasal administration was 133-fold higher than that after oral administration, and the level of cholesteryl esters in the brain significantly decreased after 7 days of administration. ACS Omega. 2019 Oct 2;4(16):16943-16955
C57BL6/J mice Intratracheal bleomycin-induced acute lung injury model Intratracheal administration 10 mg/kg Administered on day 0 and day 3, sacrificed on day 7 K-604 reduced bleomycin-induced alveolar thickening, decreased inflammatory response and macrophage activation, and improved surfactant composition. J Pharmacol Exp Ther. 2022 Sep;382(3):356-365

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.74mL

0.35mL

0.17mL

8.69mL

1.74mL

0.87mL

17.37mL

3.47mL

1.74mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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