DPAP1 Inhibitor
BI-2051
BI-2051 is a very potent inhibitor of the P. falciparum protease, DPAP1 (IC50 = 0.3 nM). It is highly selective versus the homologous human proteases CatC, CatK and CatL, and shows a good in vitro PK profile with high solubility and good cellular permeability. This compound is suitable for in vitro experiments.
More information
Dipeptidyl aminopeptidase 1 (DPAP1) is a cysteine exopeptidase expressed in the food vacuoles of the parasite Plasmodium falciparum1.
P. falciparum uses the hemoglobin in the host erythrocytes as a source of amino acids and this catabolism is essential for the intraerythrocytic growth of the parasite. Hemoglobin is taken up by the cytostome and delivered into the food vacuole. In the food vacuole, hemoglobin is degraded by aspartic, cysteine and metalloproteases. DPAP1 catalyzes the final step, the release of small peptides or amino acids from globin-derived oligopeptides.1 DPAP1 is therefore a potential target to interfere with the growth of P. falciparum during the erythrocytic phase of its life cycle2.
DPAP1 shows significant sequence homology to the human protease Cathepsin C (CatC).
BI-2051, 3D conformation
BI-2051 displays an IC50 = 0.3 nM in a DPAP1 assay using recombinant protein.
Probe name / negative control | BI-2051 | BI-2054 |
| MW [Da]a | 324.4 | 324.4 |
| DPAP1 (IC50) [nM]b | 0.3 | 204.5 |
| Human CatC (IC50) [nM]b | 2.7 | >30,000 |
| Human CatK (IC50) [nM]b | 4.3 | n.a. |
| Human CatL (IC50) [nM]b | >100,000 | 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
bAssay conditions for the CatC assay are available in the patent WO2014140075. For DPAP1, CatK, and CatL the assay conditions are identical except for the enzyme nature, concentration, buffer and substrates. More detailed experimental conditions can always be obtained via the “Contact us” form.
- For DPAP1, the substrate is H-Pro-Arg-AMC
- For CatC, the substrate is Gly-Arg-AMC
- For CatL, the substrate is Z-Phe-Arg-AMC
- For CatK, the substrate is Z-Gly-Pro-Arg-AMC
BI-2051 is a highly soluble and permeable compound. It has good in vitro PK properties in rats, but displays a weaker microsomal stability in mice.
Probe name / negative control | BI-2051 | BI-2054 |
| logP @ pH 11 | 2.6 | 2.6 |
| Solubility @ pH 6.8 [µg/ml] | >70 | >103 |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 53.7 | 27 |
| Caco-2 efflux ratio | 0.45 | 1.3 |
| MDCK permeability Pappa-b/b-a @ 1µM [10-6 cm/s] | n.d. | n.a. |
| MDCK efflux ratio | n.d. | n.a. |
| Microsomal stability (human/mouse/rat) [% QH] | <23 / 40 / 29 | n.a. |
| Hepatocyte stability @ 5% plasma (human/mouse/rat) [% QH] | 25 / n.d. / n.d. | n.a. |
| hERG [inh. % @ 10 µM] | 59, 7 | n.a. |
| CYP 3A4 (IC50) [µM] | >50 | >50 |
| CYP 2C8 (IC50) [µM] | >50 | >50 |
| CYP 2C9 (IC50) [µM] | >50 | >50 |
| CYP 2C19 (IC50) [µM] | >50 | >50 |
| CYP 2D6 (IC50) [µM] | 44.4 | 24.5 |
BI-2054 can be used as a negative control. It is the distomer of active probe BI-2051.
BI-2054 serves as a negative control
BI-2051 is > 8000x selective for P. falciparum DPAP1 versus the homologous human enzymes CatC, CatK and CatL.
BI-2051 and its negative control BI-2054 were tested on 44 targets in a selectivity panel and showed ≥1,000-fold selectivity for all targets (≤ 50% inhibition @ 10 µM).
| SELECTIVITY DATA AVILABLE | BI-2051 | BI-2054 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
BI-2051_selectivityData_0.xlsx
BI-2054_selectivityData.xlsx
BI-2051 is a very potent and highly selective dipeptidyl aminopeptidase 1 (DPAP1) inhibitor. BI-2051 inhibits recombinant P. falciparum DPAP1 with an IC50 of 0.3 nM. BI-2051 is highly soluble at pH 2.2, 4.5, 7 and displays good in vitro PK properties in rats.
2 D structure formats available
When you plan a publication, please use the following acknowledgement:
BI-2051 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.