| Hazard Information | Back Directory | [Uses]
ML204 hydrochloride is a novel, potent, selective TRPC4/TRPC5 channel inhibitor, with at least 19-fold selectivity against TRPC6 and no appreciable effect on all other TRP channels, nor on voltage-gated sodium, potassium, or Ca2+ channels[1][2]. | [Biological Activity]
ML204 is a potent and selective inhibitor of TRPC4/TRPC5 channels with 20-fold selectivity over TRPC6, without affecting other TRP channels and voltage-gated sodium, potassium or Ca2+ channels. | [in vitro]
ML204 inhibits TRPC4β-mediated intracellular Ca 2+ rise with an IC 50 value of 0.96 μM (HEK293 cells) and exhibits 19-fold selectivity against muscarinic receptor-coupled TRPC6 channel activation.
It blocks TRPC4β activity induced through either G i/o stimulation by μ-opioid, 5HT 1A serotonin, and M 2 muscarinic receptors or G q/11 stimulation by the endogenous M 3 -like muscarinic receptors.
It blocks LPS-induced TRPC5 channel activity.
| [in vivo]
ML204 (1 mg/kg; sc; twice a day; for 5 days) causes mortality associated with exacerbated hypothermia and decreases peritoneal leukocyte numbers and cytokines in LPS-injected mice.
| Animal Model: | Nonfasted male C57BL/6 (2-3 months) | | Dosage: | 1 mg/kg | | Administration: | < td class="col2"> Subcutaneous injection, twice a day, for 5 days (prior to LPS injection) | Result: | < td class="col2"> Induces mortality associated with increased hypothermia in mice with LPS-induced systemic inflammatory response. | [target]
| TRPC4 | TRPC5 | [IC 50]
TRPC4; TRPC5 | [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. DOI:10.1074/jbc.M111.274167
[2] Miller MR, et al. Novel Chemical Inhibitor of TRPC4 Channels. Probe Reports from the NIH Molecular Libraries Program. PMID:22049577
[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. DOI:10.1172/JCI71165
[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. DOI:10.1155/2018/4904696 |
|
| Company Name: |
ChemeGen 中国
|
| Tel: |
18818260767 |
| Website: |
https://www.chemegen.com |
| Company Name: |
InvivoChem
|
| Tel: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
| Company Name: |
ABBIOCHEM
|
| Tel: |
18964309092 18964309092 |
| Website: |
http://www.abbiochemical.com |
| Company Name: |
MedChemExpress
|
| Tel: |
021-58955995 |
| Website: |
www.medchemexpress.com |
|
|
Tags:2070015-10-8
Related Product Information
|
|
1550008-55-3
1919853-46-5
1883510-31-3
381168-77-0
489402-47-3
1360705-96-9
1928763-08-9
1417700-13-0
1443246-62-5
1991986-30-1
19992-50-8
1401242-74-7
878978-76-8
1422269-30-4
1417699-67-2
1357171-62-0
877636-42-5
100872-83-1
|
|