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Page 8 of 17 Stojkovska Docevska et al. Rare Dis Orphan Drugs J 2023;2:14 https://dx.doi.org/10.20517/rdodj.2023.09

Table 1. Selected synthetic inhibitors of human cathepsin C
Warhead /
Identifier Structure Potency
Type of inhibition
AZD5248 Nitrile/reversible pIC = 9.1 ± 0.1
50
(in vitro)
pIC = 8.1 ± 0.1
50
(cell-based assay)
AZD7986 Nitrile/reversible pIC = 8.4 ± 0.17
50
(in vitro)
pIC = 6.84 ± 0.33
50
(cell-based assay)
IcatC Nitrile/reversible IC = 15 ± 1 nM
50
GSK2793660 α,β-unsaturated amide/irreversible IC = 0.43-1 nM
50

[115]
Compound 54 in ref. Pyridine/reversible IC = 57.4 ± 0.7 nM
50

4
-1 -1
Compound 11 in ref. [117] Epoxide/irreversible k inact = (5.6 ± 1.7) × 10 M s

[121]
Compound 8 in ref. Semicarbazide/reversible IC = 31 ± 3 nM
50
K = 45 ± 2 nM
i

[122]
Compound 3c in ref. Phosphonate K = 23 ± 12 nM
i
(non-covalent)/reversible
[122]
Compound 4a in ref. Phosphonate K = 51 ± 16 nM
i
(non-covalent)/reversible
Canertinib Acrylamide/irreversible IC = 0.12 μM
50

[125]
Compound 22 in ref. Acrylamide/irreversible IC = 17.3 ± 0.9 nM
50
(in vitro)
IC = 1-5 nM
50
(cell-based assay)

neutrophil progenitor cells from human bone marrow with a pIC value of 6.84 ± 0.33 and had favorable
50
predicted plasma stability and clearance rate .
[103]