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Chemical Structure| 1222781-70-5 Chemical Structure| 1222781-70-5

Structure of ML133 HCl
CAS No.: 1222781-70-5

Chemical Structure| 1222781-70-5

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ML133 HCl selectively inhibit Kir2.1 with IC50 of 1.8 μM at pH7.4 and 290 nM at pH8.5 and has no effect on Kir1.1 and weak activity for Kir4.1 and Kir7.1.

Synonyms: ML-133 (hydrochloride); ML133 hydrochloride

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Product Details of ML133 HCl

CAS No. :1222781-70-5
Formula : C19H20ClNO
M.W : 313.82
SMILES Code : COC1=CC=C(C=C1)CNCC2=C3C=CC=CC3=CC=C2.[H]Cl
Synonyms :
ML-133 (hydrochloride); ML133 hydrochloride
MDL No. :MFCD20921521
InChI Key :NGQIBUUFXDPHKT-UHFFFAOYSA-N
Pubchem ID :44247466

Safety of ML133 HCl

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H315-H318-H335-H400
Precautionary Statements:P261-P273-P280-P305+P351+P338
Class:9
UN#:3077
Packing Group:

Isoform Comparison

Biological Activity

Target
  • Potassium Channel

    Kir2.1, IC50:290 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Endothelial cells 20 μM Inhibition of Kir2.1 channel currents J Physiol. 2016 Jun 15;594(12):3271-85.
Rat microglia 20 μM 5 minutes ML133 significantly reduced CRAC-mediated Ca2+ influx Front Cell Neurosci. 2015 May 12;9:185.
Spinal dorsal horn lamina IIi neurons 100 μmol/L ML133 significantly increased the frequency of glycinergic spontaneous inhibitory postsynaptic currents (gly-sIPSCs) but did not affect their amplitude. Neurosci Bull. 2019 Apr;35(2):301-314.
Human pulmonary artery smooth muscle cells (HPASMCs) 20 µM 24 hours ML133 reversed PDGF-BB-induced proliferation and migration of HPASMCs, inhibited the expression of OPN and PCNA, and suppressed the TGF-β1/SMAD2/3 signaling pathway. Int J Mol Med. 2022 Sep;50(3):119.
Murine colonic smooth muscle cells (SMC) 10 μM To investigate the effect of ML133 on inward currents in SMC, results showed that ML133 did not significantly inhibit the inward currents J Physiol. 2018 Feb 1;596(3):379-391.
Murine colonic ICC 10 μM To investigate the inhibitory effect of ML133 on inward rectifier K+ currents in ICC, results showed that ML133 significantly inhibited the inward current activated by elevated [K+]o J Physiol. 2018 Feb 1;596(3):379-391.
Layer III pyramidal neurons 30 μM ML133 is a specific antagonist for the Kir2 subfamily, used to study the hyperpolarization induced by NOP via Kir channels. Results showed that ML133 significantly inhibited Kir channel currents at negative potentials but had no significant effect on NOP-induced hyperpolarization at resting membrane potentials. Neuropharmacology. 2019 Jun;151:144-158.
BV-2 microglial cells 20 μM 24 hours To investigate the effect of ML133 on IFNγ-induced priming of microglial ROS production. Results showed that ML133 significantly inhibited the IFNγ-induced enhancement of ROS production. PLoS One. 2016 Sep 6;11(9):e0162497.
Spino-PB neurons 100 µM ML133 inhibits Kir2 channels, increases spontaneous activity, depolarizes RMP, reduces rheobase and AP amplitude Neuroscience. 2016 Dec 17;339:502-510.
HEK293 cells 10 μM To identify modulators of K ir2.1 function, ML133 was found as a potent inhibitor ACS Chem Biol. 2011 Aug 19;6(8):845-56.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6J mice Spared nerve injury (SNI) model Intrathecal administration 3 nmol, 10 nmol, 30 nmol Pretreatment 30 min before SNI surgery or once daily from days 5 to 7 post-surgery ML133 pretreatment dose-dependently inhibited SNI-induced dynamic mechanical allodynia but had no effect on punctate allodynia. Acute ML133 perfusion enhanced glycinergic transmission in spinal dorsal horn lamina IIi neurons. Neurosci Bull. 2019 Apr;35(2):301-314.
Mice Murine colonic muscle strips 10 μM and 30 μM To investigate the effect of ML133 on resting membrane potential in intact colonic muscles, results showed that ML133 caused depolarization of cells J Physiol. 2018 Feb 1;596(3):379-391.
Mice EC-specific Kir2.1 channel knockdown (EC- Kir2.1−/−) mice 20 μM Inhibition of Kir2.1 channel function, reducing vasodilatory responses J Physiol. 2016 Jun 15;594(12):3271-85.
Wistar rats Mesenteric artery In vitro experiment 20 μmol/L ML133 attenuated S-1 or ML213-mediated vasorelaxation by inhibiting K IR2 channels Front Physiol. 2020 Dec 7;11:598779

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.19mL

0.64mL

0.32mL

15.93mL

3.19mL

1.59mL

31.87mL

6.37mL

3.19mL

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

References

 

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