Synonym
ACT-709478; ACT709478; ACT 709478; apinocaltamide
IUPAC/Chemical Name
N-(1-((5-Cyanopyridin-2-yl)methyl)-1H-pyrazol-3-yl)-2-(4-(1-(trifluoromethyl)cyclopropyl)-phenyl)acetamide
InChi Key
LSYANGLAZUZYFX-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H18F3N5O/c23-22(24,25)21(8-9-21)17-4-1-15(2-5-17)11-20(31)28-19-7-10-30(29-19)14-18-6-3-16(12-26)13-27-18/h1-7,10,13H,8-9,11,14H2,(H,28,29,31)
SMILES Code
O=C(NC1=NN(CC2=NC=C(C#N)C=C2)C=C1)CC3=CC=C(C4(C(F)(F)F)CC4)C=C3
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:
ACT-709478 is a potent, selective, orally active, and brain penetrating T-type calcium channel blocker.
In vivo activity:
In WAG/Rij rats, 10 mg/kg po of 66b (ACT-709478), 66d, or 66e significantly decreased the cumulative duration of absence-like seizures over the next 12 h period by 93, 35, and 79%, respectively, compared to a matched vehicle group (p < 0.001 for 66b and 66e and p < 0.01 for 66d, paired t test, Figure 5a,c,e). Compounds 66b and 66e completely suppressed the absence-type seizures over the first 6 h following administration (Figure 5a,e).
Reference: J Med Chem. 2017 Dec 14;60(23):9769-9789. https://pubmed.ncbi.nlm.nih.gov/29116786/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
125.0 |
293.83 |
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
425.42
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. Bezençon O, Heidmann B, Siegrist R, Stamm S, Richard S, Pozzi D, Corminboeuf O, Roch C, Kessler M, Ertel EA, Reymond I, Pfeifer T, de Kanter R, Toeroek-Schafroth M, Moccia LG, Mawet J, Moon R, Rey M, Capeleto B, Fournier E. Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies. J Med Chem. 2017 Dec 14;60(23):9769-9789. doi: 10.1021/acs.jmedchem.7b01236. Epub 2017 Nov 20. PMID: 29116786.
In vivo protocol:
1. Bezençon O, Heidmann B, Siegrist R, Stamm S, Richard S, Pozzi D, Corminboeuf O, Roch C, Kessler M, Ertel EA, Reymond I, Pfeifer T, de Kanter R, Toeroek-Schafroth M, Moccia LG, Mawet J, Moon R, Rey M, Capeleto B, Fournier E. Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies. J Med Chem. 2017 Dec 14;60(23):9769-9789. doi: 10.1021/acs.jmedchem.7b01236. Epub 2017 Nov 20. PMID: 29116786.
1: Richard M, Kaufmann P, Kornberger R, Dingemanse J. First-in-man study of ACT-709478, a novel selective triple T-type calcium channel blocker. Epilepsia. 2019 May;60(5):968-978. doi: 10.1111/epi.14732. Epub 2019 Apr 20. PMID: 31004346.
2: Richard M, Kaufmann P, Ort M, Kornberger R, Dingemanse J. Multiple-Ascending Dose Study in Healthy Subjects to Assess the Pharmacokinetics, Tolerability, and CYP3A4 Interaction Potential of the T-Type Calcium Channel Blocker ACT-709478, A Potential New Antiepileptic Drug. CNS Drugs. 2020 Mar;34(3):311-323. doi: 10.1007/s40263-019-00697-1. PMID: 31994022.
3: Nam G. T-type calcium channel blockers: a patent review (2012-2018). Expert Opin Ther Pat. 2018 Dec;28(12):883-901. doi: 10.1080/13543776.2018.1541982. Epub 2018 Nov 11. PMID: 30372652.
4: Bezençon O, Heidmann B, Siegrist R, Stamm S, Richard S, Pozzi D, Corminboeuf O, Roch C, Kessler M, Ertel EA, Reymond I, Pfeifer T, de Kanter R, Toeroek- Schafroth M, Moccia LG, Mawet J, Moon R, Rey M, Capeleto B, Fournier E. Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies. J Med Chem. 2017 Dec 14;60(23):9769-9789. doi: 10.1021/acs.jmedchem.7b01236. Epub 2017 Nov 20. PMID: 29116786.
