Nav1.2 channel blocker
BIII 890CL
BII 890CL is a highly potent, use- and voltage-dependent Nav1.2 sodium channel blocker. It has high selectivity for site 2 of the sodium channel and preferentially binds to its inactive state (IC50 = 77 nM), which makes it an excellent tool to discriminate between highly activated neurons and neurons with physiological membrane potentials. This compound is suitable for both in vitro and in vivo experiments.
More information
The voltage-gated sodium (Nav) channels are responsible for the rapid rising phase of an action potential, and thus play an essential role in membrane excitability and electrical signalling. Three distinct functional states are known: resting, active, and inactivated and all play a key role in neuronal activation. They are highly selective for the transport of sodium ions across cell membranes and become activated by a change in transmembrane voltage which is initially negatively charged. The activation results in a sodium influx and further depolarization of the neuron as the cause for an action potential. At the peak of the action potential, the sodium channels inactivate themselves by closing their inactivation gate. The neuron has to repolarize to its resting potential to bring the sodium channel back into the resting state1,2,4.
Sodium channels play a major role in signal propagation within the PNS and CNS but also in cardiac myocytes. Mutations that interfere with Na+ channel inactivation can contribute to cardiovascular diseases or epileptic seizures by over-excitation of muscle or nerve cells1,2,4.
Based on patch clamp evaluations, BII 890CL preferentially binds to the inactivated state of the sodium channel (IC50 = 77 nM). In contrast, the binding at the resting state is only 18 µM. This exceptional selectivity of more than 230-fold for the different states of the sodium channel makes this compound unique compared with other sodium channel blockers1-4.
Cryo-EM structure of Nav1.2 in complex with cynotoxin KIIIA (X. Pan et al.)5
| Probe name / negative control | BIII 890CL | BI-55CL |
| MW [Da, free base]a | 379.5 | 303.4 |
| Displacement of [3H]BTX Ki [nM] BTX: batrachotoxinb | 43 | >10.000 |
| Inhibition of veratridine induced glutamate release in rat brain slices IC50 [nM]b | 322 | n.a. |
a For the salt form you will get, please refer to the label on the vial and for the molecular weight of the salt, please refer to the FAQs
b for detailed assay conditions see reference 3
| Probe name / negative control | BIII 890CL | BI-55CL |
| Melting point (°C) | 258 | n.d. |
| logD @ pH 11 | >6 | 4.9 |
| Solubility @ pH 4 / pH 6 / pH 7 [µg/mL] | 2,560 / 1,040 / 8 | n.a. / n.a. / >70 |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | n.a. | 44 |
| Caco-2 efflux ratio | n.a. | 0.7 |
| Microsomal stability (human/mouse/rat) [% QH] | 87 / n.a. / n.a. | 62 / >88 / >88 |
| Hepatocyte stability (human/mouse/rat) [% QH] | n.a. | n.a. |
| Plasma Protein Binding (rat) [%] | 99.2 | n.a. |
| hERG [inh. % @ 1 µM] | 54 | n.a. |
| CYP 3A4 (IC50) [µM] | 11.4 | >50 |
| CYP 1A2 (IC50) [µM] | 25.5 | n.a. |
| CYP 2C9 (IC50) [µM] | 6.9 | >50 |
| CYP 2C19 (IC50) [µM] | 2.3 | 3.6 |
| CYP 2D6 (IC50) [µM] | 0.03 | >50 |
| BIII 890CL | RATA |
| tmax [h] | 2.83 |
| Cmax [nM] | 11.9 |
| AUC [nM] | 24 |
a p.o. dose: 3 mg/kg
In animal studies such as the maximum electrical shock model it could be demonstrated that the compound supresses tonic seizures at doses which do not interfere with physiological functions of the sodium channel.
Maximum electroshock (MES) test in mice ID50 = 6.1 mg/kg3.
With BI-55CL we offer a structurally close analogue with more than 1000 fold lower potency for site 2 of the sodium channel (Ki ~ 10 µM; [3H]-BTX).
With BIII 890CL, we offer a structurally close analogue, BI-55CL, with more than 1,000-fold lower potency for site 2 of the sodium channel (Ki ~ 10 µM; [3H]-BTX). Although the selectivity between the two states of the sodium channel has not been fully determined, the compound can be used as a comparator compound in in vitro studies1-4.
BI-55CL which serves as a negative control
| SELECTIVITY DATA AVILABLE | BIII 890CL | BI-55CL |
SafetyScreen44™ with kind support of  | Yes | Yes |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
BIII890CL_selectivityData_0.xlsx
BI-355CL_selectivityData.xlsx
For a review on voltage-gated sodium channel blockers please see reference 6.
BIII 890CL (crobenetine) is a highly potent and selective Nav1.2 sodium channel blocker that can be used as tool compound to test biological hypotheses in vitro and in vivo.
Potent blockade of sodium channels and protection of brain tissue from ischemia by BIII 890CL
Carter A. J., Grauert M., Pschorn U., Bechtel W. D., Bartmann-Lindholm C., Qu Y., Scheuer T., Catterall W. A., Weiser T.
Proceedings of the National Academy of Sciences of the United States of America 2000, 97, 4944-4949.
When you plan a publication, please use the following acknowledgement:
BIII 890CL (crobenetine) was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.