Table 3 Identified drug candidates in preclinical development with targets in the kallikrein-kinin system
From: Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system
Drug candidate | Class | Intended indication | Year of latest publication | Refs. |
|---|---|---|---|---|
Prolylcarboxypeptidase | ||||
UM8190 | Small molecule inhibitor | Thromboprophylaxis, obesity | 2012 | [51] |
Coagulation factor XII | ||||
3F7 | Recombinant antibody (fully human) | Thromboprophylaxis | 2022 | [26] |
ALN-F12 | siRNA | Hereditary angioedema (prophylaxis) | 2019 | [38] |
Thromboprophylaxis | 2020 | [37] | ||
ARC-F12 | siRNA | Hereditary angioedema (prophylaxis) | (2016) | [39] |
Thromboprophylaxis | (2016) | [39] | ||
COU254 | Small molecule inhibitor | Acute ischemic stroke | 2010 | [42] |
FXII900 | Peptide inhibitor | Thromboprophylaxis | 2021 | |
KV998086 | Small molecule inhibitor | Hereditary angioedema (on-demand) | (2022) | |
rHA-Infestin-4 | Inhibitor, protein | Acute ischemic stroke | 2016 | |
DX-4012 | Monoclonal antibody (fully human) | Thromboprophylaxis | (2015) | [36] |
Sylvestin | Peptide inhibitor | Acute ischemic stroke | 2022 | [47] |
Plasma (P) and tissue (T) kallikrein | ||||
CU-2010 (P) | Small molecule inhibitor | Prevention of blood loss in cardiac surgery | 2009 | [99] |
Ecallantide/DX-88 (P) | Inhibitor, protein | Cerebral ischemia | 2006 | [85] |
KV998052 (P) | Small molecule inhibitor | Acute respiratory distress syndrome | (2021) | [79] |
Retinal edema | (2022) | [80] | ||
KV998054 (P) | Small molecule inhibitor | Retinal edema | (2019) | [80] |
VA999272 (P) | Small molecule inhibitor | Retinal edema | 2016 | [81] |
VE-3539 (P) | Small molecule inhibitor | Diabetic retinopathy | (2018) | [83] |
VE-4840 (P) | Small molecule inhibitor | Retinal edema | (2019) | [82] |
DX-2300 (T) | Monoclonal antibody (fully human) | Airway diseases | 2009 | [86] |
Bradykinin B2 receptor | ||||
Bradyzide | Small molecule inhibitor | Inflammatory hyperalgesia | 2009 | [133] |
FR173657 | Small molecule inhibitor | Skin inflammatory diseases | 2009 | |
LF 18-1505T | Small molecule inhibitor | Closed head trauma | 2006 | [131] |
FR-190997 | Small molecule partial agonist | Ocular hypertension | 2014 | [139] |
NG291 | Peptide agonist | Disruption of blood brain barrier | 2021 | |
R523 | Peptide agonist | Glioma | 2010 | [138] |
Bradykinin B1 receptor | ||||
B 9430 | Peptide antagonist | Cerebral ischemia | 2000 | [156] |
B 9858 | Peptide antagonist | Inflammatory hyperalgesia | 2002 | [151] |
BI 113823 | Small molecule antagonist | Chronic liver fibrosis | 2022 | [155] |
ELN441958 | Small molecule antagonist | Inflammatory hyperalgesia | 2007 | [152] |
MK-0686 | Small molecule antagonist | Chronic pain | 2007 | [149] |
NVP-SAA164 | Small molecule antagonist | Inflammatory hyperalgesia | 2005 | [150] |
R-715 | Peptide antagonist | Skin inflammatory diseases | 2009 | [153] |
R-954 | Peptide antagonist | Diabetic retinopathy | 2018 | [148] |
SSR240612 | Small molecule antagonist | Skin inflammatory diseases | 2009 | |
NG29 | Peptide agonist | Glioma | 2016 | |