sEH inhibitor
BI-1935
BI-1935 is a potent small molecule inhibitor of soluble epoxide hydrolase (sEH) (IC50 = 7 nM). It showed good selectivity against hCYP epoxygenases 2J2/2C9/2C19 and IL-2. In Dahl salt-sensitive rats, BI-1935 showed a dose-dependent effect on mean arterial pressure. This compound is suitable for both in vitro and in vivo experiments.
More information
The enzyme sEH is involved in the metabolism of chemical mediators originated from arachidonic acid2,3. sEH catalyzes the hydrolysis of epoxyeicosatrienoic acids (EETs) which is derived from oxidation of arachidonic acid by CYP2J & CYP2C to the corresponding dihydroxyeicosatrienoic acids (DHETs). Inhibition of sEH is expected to increase EETs levels and thereby potentiating in vivo pharmacological effects which include anti-inflammatory and vasodilatory properties. Selective inhibition of Soluble epoxide hydrolase has been invoked to account for the antihypertensive effect of dicyclohexyl urea in the spontaneously hypertensive rat4,5. EETs elicit a vasodilatory response by acting as an endothelium derived hyperpolarizing factor that mediates vasodilatation through the stimulation of calcium-activated potassium channels in smooth muscle cells6,7,8. Selective sEH inhibitors have also shown beneficial effects in an angiotensin II-dependent model of hypertension in the Sprague–Dawley rat9, and protective action in models of hypertension induced renal damage and failure10. An sEH inhibitor significantly decreased the total bronchoalveolar lavage cell number in tobacco smoke-exposed rats, with significant reductions noted in neutrophils, alveolar macrophages, and lymphocytes in a rat model of airway inflammation11. These reports suggest that inhibition of sEH represents a potential method for the treatment of inflammatory and cardiovascular diseases1.
Human sEH in complex with a pyrazole agonist (PDB code: 3OTQ).
Probe name / negative control | BI-1935 | BI-2049 |
| MW [Da, free base]a | 498.5 | 503.5 |
| h-sEH (IC50) [nM]b | 7 | >100,000 |
| r-sEH (IC50) [nM]c | 7 | - |
| sEH_HepG2 [nM]d | <1 | - |
| sEH_RAT FPDR [nM] | 7.4 | - |
| CIL-2 [µM] | - | - |
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
bHuman and rat soluble epoxide hydrolase inhibition
cRat soluble epoxide hydrolase inhibition
dCellular assay for inhibition of sEH in human Hep G2 Cells, ELISA readout
| Probe name | BI-1935 | BI-2049 |
| logD @ pH 11 | 3 | 5.5 |
| Solubility @ pH 7 [µg/mL] | 32 | Not fully soluble |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 32 | n.d. |
| Caco-2 efflux ratio | 1 | n.d. |
| Microsomal stability (human/mouse/rat) [%QH] | 48 / 50 / 45 | 34 / - / 33 |
| Hepatocyte stability (human/mouse/rat) [%QH] | 28 / 95 / 84 | n.d. |
| Plasma Protein Binding (human/rat) [%] | 97.7 / 99.1 | >99 / n.d. |
| CYP 2J2 [µM] | 3 | n.d. |
| CYP 2C9 [µM] | 4.1 | n.d. |
| CYP 3A4 [µM] | >50 | n.d. |
| CYP 2D6 | >50 | n.d. |
| BI-1935 | RAT |
| Clearence [mL/min/kg]a | 4.1 |
| Mean residence time after i.v. dose [h]a | 3 |
| tmax [h]b | 2.7 |
| Cmax [µM]b | 10670 |
| F [%] | 100 |
| Vss [l/kg]a | 0.5 |
a i.v. dose: 0.6 mg/kg
b p.o. dose: fasted 1.5 mg/kg
The molecule BI-2049 can be used as in vitro negative control (IC50 h-sEH > 3 µM)
BI-2049, negative control
Until 21.03.2018, the compound BI-64BS was offered on opnMe.com as in vitro negative control (IC50 h-sEH ≥ 100 µM) which was replaced by BI-2049 which is structurally more similar to BI-1935.
Structure of BI-64BS
A Boehringer Ingelheim in-house screen of BI-1935 against hCYP epoxygenases 2J2/2C9/2C19 and IL-2 showed > 100-fold selectivity (> 1µM for all).
Eurofins Safety Panel 44™ was measured against 67 targets (please refer to supplementary data). 61/67 < 20% Inhibition @ 10 µM, 5/67 < 80% Inhibition @ 10 µM, Thromboxane Synthase 96% inhibition @ 10 µM (IC50 = 0.132 µM). 5LO (5-Lipoxygenase) 66% inhibition @ 10 µM (IC50 = 5.92 µM).
| SELECTIVITY DATA AVILABLE | BI-1935 | BI-2049 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| PDSP13 | Yes | Yes |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
BI-1935_selectivityData.xlsx
BI-2049_selectivityData.xlsx
For a review on sEH inhibitors please refer to reference 12
BI-1935 is a potent and selective small molecule inhibitor of the enzyme Soluble epoxide hydrolase (sEH) and can be used as in vitro or in vivo tool compound.
Epoxyeicosatrienoic and dihydroxyeicosatrienoic acids dilate human coronary arterioles via BK(Ca) channels: implications for soluble epoxide hydrolase inhibition
Larsen B. T., Miura H., Hatoum O. A., Campbell W. B., Hammock B. D., Zeldin D. C., Falck J. R., Gutterman D. D.
Am. J. Physiol. Heart Circ. Physiol. 2006, 290, H491-499.
When you plan a publication, please use the following acknowledgement:
BI-1935 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.