ICA069673
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MedKoo CAT#: 530943

CAS#: 582323-16-8

Description: ICA069673 is a heteromeric Kv7 channel activator. It is selective for Kv7.2/7.3 over Kv7.3/7.5 (EC50s = 0.69 and 14.3 μM, respectively). ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. . ICA-069673 decreased the global intracellular Ca(2+) concentration in DSM cells, an effect blocked by the L-type Ca(2+) channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991.


Chemical Structure

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ICA069673
CAS# 582323-16-8

Theoretical Analysis

MedKoo Cat#: 530943
Name: ICA069673
CAS#: 582323-16-8
Chemical Formula: C11H6ClF2N3O
Exact Mass: 269.02
Molecular Weight: 269.636
Elemental Analysis: C, 49.00; H, 2.24; Cl, 13.15; F, 14.09; N, 15.58; O, 5.93

Price and Availability

Size Price Availability Quantity
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2650 2 Weeks
1g USD 3650 2 Weeks
2g USD 5950 2 Weeks
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Synonym: ICA-069673; ICA 069673; ICA069673.

IUPAC/Chemical Name: N-(2-chloro-5-pyrimidinyl)-3,4-difluoro-benzamide

InChi Key: IIBSHMFXVWTQSJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C11H6ClF2N3O/c12-11-15-4-7(5-16-11)17-10(18)6-1-2-8(13)9(14)3-6/h1-5H,(H,17,18)

SMILES Code: O=C(NC1=CN=C(Cl)N=C1)C2=CC=C(F)C(F)=C2

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:
Biological target: ICA-069673 is a KCNQ2/Q3 potassium channel activator with an IC50 of 0.69 μM.
In vitro activity: These experiments reveal that KCNQ2 residues F168 and A181 in the S3 segment are essential determinants of ICA73 (ICA-069673) subtype specificity. Mutations at either position in KCNQ2 abolish the ICA73-mediated gating shift, but preserve RTG sensitivity. Interestingly, A181P mutant channels show little ICA73-mediated gating shift but retain current potentiation by the drug. Mutations (L198F and P211A), which introduce these critical KCNQ2 residues at corresponding positions in KCNQ3, transplant partial ICA73 sensitivity. These findings demonstrate that RTG and ICA73 act via distinct mechanisms, and also reveal specific residues that underlie subtype specificity of KCNQ channel openers. Reference: J Physiol. 2017 Feb 1;595(3):663-676. https://pubmed.ncbi.nlm.nih.gov/27506413/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DNF 30.0 111.26
DMSO 36.2 134.40
Ethanol 30.3 112.18

Preparing Stock Solutions

The following data is based on the product molecular weight 269.64 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. Wang AW, Yang R, Kurata HT. Sequence determinants of subtype-specific actions of KCNQ channel openers. J Physiol. 2017 Feb 1;595(3):663-676. doi: 10.1113/JP272762. Epub 2016 Sep 23. PMID: 27506413; PMCID: PMC5285613. 2. Provence A, Malysz J, Petkov GV. The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility. J Pharmacol Exp Ther. 2015 Sep;354(3):290-301. doi: 10.1124/jpet.115.225268. Epub 2015 Jun 18. PMID: 26087697; PMCID: PMC4538873.
In vitro protocol: 1. Wang AW, Yang R, Kurata HT. Sequence determinants of subtype-specific actions of KCNQ channel openers. J Physiol. 2017 Feb 1;595(3):663-676. doi: 10.1113/JP272762. Epub 2016 Sep 23. PMID: 27506413; PMCID: PMC5285613. 2. Provence A, Malysz J, Petkov GV. The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility. J Pharmacol Exp Ther. 2015 Sep;354(3):290-301. doi: 10.1124/jpet.115.225268. Epub 2015 Jun 18. PMID: 26087697; PMCID: PMC4538873.
In vivo protocol: TBD

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1: Provence A, Malysz J, Petkov GV. The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility. J Pharmacol Exp Ther. 2015 Sep;354(3):290-301. doi: 10.1124/jpet.115.225268. Epub 2015 Jun 18. PubMed PMID: 26087697; PubMed Central PMCID: PMC4538873.

2: Vicente-Baz J, Lopez-Garcia JA, Rivera-Arconada I. Effects of novel subtype selective M-current activators on spinal reflexes in vitro: Comparison with retigabine. Neuropharmacology. 2016 Oct;109:131-8. doi: 10.1016/j.neuropharm.2016.05.025. Epub 2016 Jun 2. PubMed PMID: 27263036.

3: Brueggemann LI, Haick JM, Cribbs LL, Byron KL. Differential activation of vascular smooth muscle Kv7.4, Kv7.5, and Kv7.4/7.5 channels by ML213 and ICA-069673. Mol Pharmacol. 2014 Sep;86(3):330-41. doi: 10.1124/mol.114.093799. Epub 2014 Jun 18. PubMed PMID: 24944189; PubMed Central PMCID: PMC4152906.

4: Wang AW, Yang R, Kurata HT. Sequence determinants of subtype-specific actions of KCNQ channel openers. J Physiol. 2017 Feb 1;595(3):663-676. doi: 10.1113/JP272762. Epub 2016 Sep 23. PubMed PMID: 27506413; PubMed Central PMCID: PMC5285613.

5: Amato G, Roeloffs R, Rigdon GC, Antonio B, Mersch T, McNaughton-Smith G, Wickenden AD, Fritch P, Suto MJ. N-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy. ACS Med Chem Lett. 2011 Mar 31;2(6):481-4. doi: 10.1021/ml200053x. eCollection 2011 Jun 9. PubMed PMID: 24900334; PubMed Central PMCID: PMC4018159.

6: Rivera-Arconada I, Vicente-Baz J, Lopez-Garcia JA. Targeting Kv7 channels in pain pathways. Oncotarget. 2017 Feb 21;8(8):12554-12555. doi: 10.18632/oncotarget.15261. PubMed PMID: 28199957; PubMed Central PMCID: PMC5355034.