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