ML204

Alias: ML204; ML-204; ML 204
Cat No.:V4004 Purity: ≥98%
ML204 is a novel, potent, and selective TRPC4 (Transient receptor potential canonical) channel inhibitor identified from high throughput fluorescent screen of 305,000 compounds of the Molecular Libraries Small Molecule Repository for inhibitors that blocked intracellular Ca(2+) rise in response to stimulation of mouse TRPC4β by μ-opioid receptors.
ML204 Chemical Structure CAS No.: 5465-86-1
Product category: TRP Channel
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of ML204:

  • ML204 HCl
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

ML204 is a novel, potent, and selective TRPC4 (Transient receptor potential canonical) channel inhibitor identified from high throughput fluorescent screen of 305,000 compounds of the Molecular Libraries Small Molecule Repository for inhibitors that blocked intracellular Ca(2+) rise in response to stimulation of mouse TRPC4β by μ-opioid receptors. ML204 inhibited TRPC4β-mediated intracellular Ca(2+) rise with an IC(50) value of 0.96 μm and exhibited 19-fold selectivity against muscarinic receptor-coupled TRPC6 channel activation. In whole-cell patch clamp recordings, ML204 blocked TRPC4β currents activated through either μ-opioid receptor stimulation or intracellular dialysis of guanosine 5'-3-O-(thio)triphosphate (GTPγS), suggesting a direct interaction of ML204 with TRPC4 channels rather than any interference with the signal transduction pathways. Selectivity studies showed no appreciable block by 10-20 μm ML204 of TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and native voltage-gated sodium, potassium, and calcium channels in mouse dorsal root ganglion neurons. In isolated guinea pig ileal myocytes, ML204 blocked muscarinic cation currents activated by bath application of carbachol or intracellular infusion of GTPγS, demonstrating its effectiveness on native TRPC4 currents. Therefore, ML204 represents an excellent novel tool for investigation of TRPC4 channel function and may facilitate the development of therapeutics targeted to TRPC4.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
ML204 has a 19-fold coupling to muscarinic receptor-coupled TRPC6 channel activation and inhibits TRPC4β-mediated intracellular Ca2+ rise with an IC50 value of 0.96 μM (HEK293 cells) [1]. The activation of Gq/11 by the M2 muscarinic receptor or endogenous M3-like muscarinic receptor, u-opioid, 5HT1A hematin, Gi/o, and TRPC4β is blocked by ML204[1]. ML204 inhibits TRPC5 channel activity that is triggered by LPS [3].
ln Vivo
In LPS-injected mice, ML204 (1 mg/kg; subcutaneous injection; twice daily; for 5 days) produced activity linked to increased hypothermia and decreased quantities of peritoneal leukocytes and cytokines [4].
Animal Protocol
Animal/Disease Models: Non-fasted male C57BL/6 (2-3 months) [4]
Doses: 1 mg/kg
Route of Administration: subcutaneous injection twice (two times) daily for 5 days (before LPS injection)
Experimental Results: LPS-small Lower body temperature in mice induces systemic inflammatory responses associated with increased mortality.
References
[1]. Miller M, et al. Identification of ML204, a novel potent antagonist that selectively modulates native TRPC4/C5 ion channels. J Biol Chem. 2011 Sep 23;286(38):33436-46.
[2]. Miller MR, et al. Novel Chemical Inhibitor of TRPC4 Channels. Probe Reports from the NIH Molecular Libraries Program .
[3]. Thomas Schaldecker, et al. Inhibition of the TRPC5 ion channel protects the kidney filter. J Clin Invest. 2013 Dec 2; 123(12): 5298–5309.
[4]. Domingos M S Pereira, et al. Transient Receptor Potential Canonical Channels 4 and 5 Mediate Escherichia coli-Derived Thioredoxin Effects in Lipopolysaccharide-Injected Mice. Oxid Med Cell Longev. 2018 Jun 10;2018:4904696.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C15H18N2
Molecular Weight
226.32
CAS #
5465-86-1
SMILES
CC1=CC(N2CCCCC2)=NC3=CC=CC=C13
Chemical Name
4-Methyl-2-(1-piperidinyl)quinoline
Synonyms
ML204; ML-204; ML 204
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)
Solubility Data
Solubility (In Vitro)
DMSO:≥ 30mg/mL
Water:N/A
Ethanol:N/A
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 4.4185 mL 22.0926 mL 44.1852 mL
5 mM 0.8837 mL 4.4185 mL 8.8370 mL
10 mM 0.4419 mL 2.2093 mL 4.4185 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.

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g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.
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Biological Data
  • ML204

    Fluorescent assay for TRPC4β channels used to identify and characterize ML204.2011 Sep 23;286(38):33436-46.

  • ML204

    Activation of heterologously expressed TRPC4 channels and its inhibition by ML204.2011 Sep 23;286(38):33436-46.

  • ML204

    ML204 blocks TRPC4 current elicited by different activation mechanisms.

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