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MedKoo Cat#: 533245 | Name: ML297
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

ML297 is a selective Kir3.1/3.2 (GIRK1/2) channel activator (IC50 values are 160, 887 and 914 nM for GIRK1/2, GIRK1/4 and GIRK1/3 respectively). ML297 exhibits no effect on GIRK2, GIRK2/3, Kir2.1 and Kv7.4 channels, and has minimal effect on a panel of other ion channels, receptors and transporters.

Chemical Structure

ML297
ML297
CAS#1443246-62-5

Theoretical Analysis

MedKoo Cat#: 533245

Name: ML297

CAS#: 1443246-62-5

Chemical Formula: C17H14F2N4O

Exact Mass: 328.1136

Molecular Weight: 328.32

Elemental Analysis: C, 62.19; H, 4.30; F, 11.57; N, 17.06; O, 4.87

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 3,850.00 2 Weeks
2g USD 5,850.00 2 Weeks
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Related CAS #
No Data
Synonym
ML297; ML 297; ML-297; Vu0456810; Vu-0456810; Vu 0456810;
IUPAC/Chemical Name
1-(3,4-difluorophenyl)-3-(5-methyl-2-phenylpyrazol-3-yl)urea
InChi Key
IEKSMUSSYJUQMY-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H14F2N4O/c1-11-9-16(23(22-11)13-5-3-2-4-6-13)21-17(24)20-12-7-8-14(18)15(19)10-12/h2-10H,1H3,(H2,20,21,24)
SMILES Code
O=C(NC1=CC(C)=NN1C2=CC=CC=C2)NC3=CC=C(F)C(F)=C3InChI=1S/C17H14F2N4O/c1-11-9-16(23(22-11)13-5-3-2-4-6-13)21-17(24)20-12-7-8-14(18)15(19)10-12/h2-10H,1H3,(H2,20,21,24)
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
ML 297 (VU 0456810) is a potent and selective GIRK1/2 activator, with an EC50 of 0.16 μM.
In vitro activity:
Modulation of hypocretin neurons by ML297 was evaluated using whole-cell current-clamp recordings of visually identified hypocretin neurons from orexin/EGFP transgenic hypothalamic brain slices. The bath-application of ML297 (10 µM) caused long-lasting hyperpolarization (−9 ± 1 mV, n = 4), decreased input resistance (43 ± 4% of control), and blocked spontaneous firing of action potentials in hypocretin neurons (Figure 1A). Reference: Sleep. 2019 Mar 1;42(3):zsy244. https://pubmed.ncbi.nlm.nih.gov/30535004/
In vivo activity:
ML297, a recently developed candidate hypnotic agent targeting a new mechanism (activating GIRK1/2-subunit containing G-protein coupled inwardly rectifying potassium [GIRK] channels), alters sleep architecture in mice over the first 6 hr following a single-trial learning event. Following contextual fear conditioning (CFC), ML297 reversed post-CFC reductions in NREM sleep spindle power and REM sleep amounts and architecture, renormalizing sleep features to what was observed at baseline, prior to CFC. Reference: Sleep. 2023 Mar 9;46(3):zsac301. https://pubmed.ncbi.nlm.nih.gov/36510822/
Solvent mg/mL mM comments
Solubility
DMF 30.0 91.37
DMSO 94.7 288.46
Ethanol 17.1 52.20
PBS (pH 7.2) 10.0 30.46
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 328.32 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Anderson A, Vo BN, Marron Fernandez de Velasco E, Hopkins CR, Weaver CD, Wickman K. Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein-Gated Inwardly Rectifying K+ Channels. Mol Pharmacol. 2021 Dec;100(6):540-547. doi: 10.1124/molpharm.121.000311. Epub 2021 Sep 9. PMID: 34503975; PMCID: PMC8626782. 2. Zou B, Cao WS, Guan Z, Xiao K, Pascual C, Xie J, Zhang J, Xie J, Kayser F, Lindsley CW, Weaver CD, Fang J, Xie XS. Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep. Sleep. 2019 Mar 1;42(3):zsy244. doi: 10.1093/sleep/zsy244. PMID: 30535004; PMCID: PMC6424090. 3. Martinez JD, Brancaleone WP, Peterson KG, Wilson LG, Aton SJ. Atypical hypnotic compound ML297 restores sleep architecture immediately following emotionally valenced learning, to promote memory consolidation and hippocampal network activation during recall. Sleep. 2023 Mar 9;46(3):zsac301. doi: 10.1093/sleep/zsac301. PMID: 36510822. 4. Nakao K, Singh M, Sapkota K, Fitzgerald A, Hablitz JJ, Nakazawa K. 5-HT2A receptor dysregulation in a schizophrenia relevant mouse model of NMDA receptor hypofunction. Transl Psychiatry. 2022 Apr 22;12(1):168. doi: 10.1038/s41398-022-01930-0. PMID: 35459266; PMCID: PMC9033804.
In vitro protocol:
1. Anderson A, Vo BN, Marron Fernandez de Velasco E, Hopkins CR, Weaver CD, Wickman K. Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein-Gated Inwardly Rectifying K+ Channels. Mol Pharmacol. 2021 Dec;100(6):540-547. doi: 10.1124/molpharm.121.000311. Epub 2021 Sep 9. PMID: 34503975; PMCID: PMC8626782. 2. Zou B, Cao WS, Guan Z, Xiao K, Pascual C, Xie J, Zhang J, Xie J, Kayser F, Lindsley CW, Weaver CD, Fang J, Xie XS. Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep. Sleep. 2019 Mar 1;42(3):zsy244. doi: 10.1093/sleep/zsy244. PMID: 30535004; PMCID: PMC6424090.
In vivo protocol:
1. Martinez JD, Brancaleone WP, Peterson KG, Wilson LG, Aton SJ. Atypical hypnotic compound ML297 restores sleep architecture immediately following emotionally valenced learning, to promote memory consolidation and hippocampal network activation during recall. Sleep. 2023 Mar 9;46(3):zsac301. doi: 10.1093/sleep/zsac301. PMID: 36510822. 2. Nakao K, Singh M, Sapkota K, Fitzgerald A, Hablitz JJ, Nakazawa K. 5-HT2A receptor dysregulation in a schizophrenia relevant mouse model of NMDA receptor hypofunction. Transl Psychiatry. 2022 Apr 22;12(1):168. doi: 10.1038/s41398-022-01930-0. PMID: 35459266; PMCID: PMC9033804.
1: Nimitvilai S, Lopez MF, Mulholland PJ, Woodward JJ. Ethanol Dependence Abolishes Monoamine and GIRK (Kir3) Channel Inhibition of Orbitofrontal Cortex Excitability. Neuropsychopharmacology. 2017 Mar 15. doi: 10.1038/npp.2017.22. [Epub ahead of print] PubMed PMID: 28139680. 2: Psichas A, Glass LL, Sharp SJ, Reimann F, Gribble FM. Galanin inhibits GLP-1 and GIP secretion via the GAL1 receptor in enteroendocrine L and K cells. Br J Pharmacol. 2016 Mar;173(5):888-98. doi: 10.1111/bph.13407. PubMed PMID: 26661062; PubMed Central PMCID: PMC4761093. 3: Wen W, Wu W, Weaver CD, Lindsley CW. Discovery of potent and selective GIRK1/2 modulators via 'molecular switches' within a series of 1-(3-cyclopropyl-1-phenyl-1H-pyrazol-5-yl)ureas. Bioorg Med Chem Lett. 2014 Nov 1;24(21):5102-6. doi: 10.1016/j.bmcl.2014.08.061. PubMed PMID: 25264075. 4: Wydeven N, Marron Fernandez de Velasco E, Du Y, Benneyworth MA, Hearing MC, Fischer RA, Thomas MJ, Weaver CD, Wickman K. Mechanisms underlying the activation of G-protein-gated inwardly rectifying K+ (GIRK) channels by the novel anxiolytic drug, ML297. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10755-60. doi: 10.1073/pnas.1405190111. PubMed PMID: 25002517; PubMed Central PMCID: PMC4115558. 5: Days E, Kaufmann K, Romaine I, Niswender C, Lewis M, Utley T, Du Y, Sliwoski G, Morrison R, Dawson ES, Engers JL, Denton J, Daniels JS, Sulikowski GA, Lindsley CW, Weaver CD. Discovery and Characterization of a Selective Activator of the G-Protein Activated Inward-Rectifying Potassium (GIRK) Channel. 2012 Apr 6 [updated 2013 Mar 14]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK143539/ PubMed PMID: 23762945. 6: Kaufmann K, Romaine I, Days E, Pascual C, Malik A, Yang L, Zou B, Du Y, Sliwoski G, Morrison RD, Denton J, Niswender CM, Daniels JS, Sulikowski GA, Xie XS, Lindsley CW, Weaver CD. ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice. ACS Chem Neurosci. 2013 Sep 18;4(9):1278-86. doi: 10.1021/cn400062a. PubMed PMID: 23730969; PubMed Central PMCID: PMC3778424. 7: Uchihata Y, Ando N, Ikeda Y, Kondo S, Hamada M, Umezawa K. Isolation of a novel cyclic hexadepsipeptide pipalamycin from Streptomyces as an apoptosis-inducing agent. J Antibiot (Tokyo). 2002 Jan;55(1):1-5. PubMed PMID: 11918058.