Verducatib 

Verducatib (BI 1291583) is an orally active inhibitor of cathepsin C (also known as DPP1). Verducatib restores the protease-inhibitor balance by inhibiting the activation of neutrophil serine proteases, thereby alleviating pulmonary inflammation and regulating infection responses. Verducatib significantly reduces the risk (including severe exacerbations) and frequency of acute exacerbations in bronchiectasis (BE). Verducatib also improves lung function and quality of life, and shortens the duration of antibiotic use. The overall incidence of adverse events of Verducatib is comparable to that of placebo, with only slightly more mild-to-moderate cutaneous adverse events observed in the high-dose group, demonstrating promising clinical application potential^[1][2].

Verducatib (BI 1291583) (0.08, 0.4, 2, 10, 50 nM, pH 4.5) binds to recombinant human cathepsin C (CatC) in a reversible covalent manner, with binding kinetic parameters of k_on 6.36×10⁶ M^-1s^-1, k_off 2.29×10^-3 s^-1, an equilibrium dissociation constant K_D of 0.43 nM, and a binding half-life t_1/2 of 5.19 min^[3].
Verducatib (0.064-1000 nM; 48 h) concentration-dependently inhibits the production of active neutrophil elastase (NE) in human neutrophil progenitor U937 cells, with an IC₅₀ of 0.7 nM. It shows no obvious cytotoxicity against U937 cells, with cell viability higher than 93% at all tested concentrations and an average cell viability of 98% at the highest concentration of 1000 nM^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Verducatib (BI 1291583) (0.005-5 mg/kg; p.o.; twice daily) dose-dependently inhibits the production of active neutrophil elastase (NE) and cathepsin G (CatG) in neutrophils within bronchoalveolar lavage fluid (BALF) in a lipopolysaccharide (LPS)-induced pulmonary neutrophil infiltration model of female Crl:NMRI mice, with maximum inhibition rates reaching 97% and 99%, respectively. The ED₉₉ for NE inhibition is 1.5 mg/kg^[3].
Verducatib (single dose; p.o.) exhibits rapid distribution to the target tissue bone marrow and slow clearance in the pharmacokinetic models of healthy mice and rats. Even at low doses, it achieves a distribution profile where bone marrow exposure is significantly higher than plasma exposure, and this property shows no obvious interspecies difference between the two species^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

530.63

C₃₁H₃₅FN₄O₃

1887236-33-0

Solid

White to off-white

FC1=C(C[C@@H](C#N)NC([C@@H]2[C@]3([H])C[C@](CC3)([H])N2)=O)C=CC(C4=CC=C5COC6(CCN(C7COC7)CC6)C5=C4)=C1

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Chalmers J D, et al. Study design of a Phase III study (AIRTIVITY) of the novel dipeptidyl peptidase 1 (cathepsin C) inhibitor verducatib in people with bronchiectasis[J]. Pneumologie, 2026, 80(S 01): P 2026-464.

  [2]. Kreideweiss S, et al. BI 1291583: a novel selective inhibitor of cathepsin C with superior in vivo profile for the treatment of bronchiectasis[J]. Inflammation Research, 2023, 72(8): 1709-1717.

  [3]. Chalmers J D, et al. AIRLEAF®–a study of verducatib as a new kind of treatment for bronchiectasis: a plain language summary[J]. Future Rare Diseases, 2025, 5(1): 2580913.