TABLE 2

Summary of NLRP3 inhibition efficacy by MCC950 in nonclinical models of disease

By Organ/TypePathologyModelMCC950 DosingReference
BrainParkinson6-OHDAPO, 20 mg/kgGordon et al. (2018)
PFF α-synucleinDrinking water, 0.3 ml mg/mlGordon et al. (2018)
MitoparkPO, 20 mg/kgGordon et al. (2018)
AlzheimerAAP/PS1i.p., 10 mg/kgDempsey et al. (2017)
AβO infusion modelInfusion pump, 1 mgFekete et al. (2018)
McGill-R-Thy1-APP TG rat model of amyloidosisi.p., 15 mg/mgQi et al. (2018)
Sporadic Alzheimer disease modeli.p., 50 mg/kgHe et al. (2020)
SAMP8 modeli.p., 10 mg/kgLi et al. (2020b)
Tau seedingInfusion pump, 0.5 µMStancu et al. (2019)
Age-related cognitive impairmentLPS challenge of aged micei.p., 10 µg/gBeyer et al. (2020)
Frontotemporal dementiaTau knock-in (PLB2TAU) modeli.p., 20 mg/kgHull et al. (2020)
Traumatic brain injuryCCI mouse model of TBIi.p., 50 mg/kgIsmael et al. (2018a); Xu et al., (2018d)
Mechanical trauma by steel weighti.p., 10 mg/kgChen et al. (2019c)
Diffuse axonal injury in ratsi.p., 10 mg/kgZhao et al. (2020)
Intracerebral hemorrhageInjection of autologous blood modeli.p., 10 mg/kgRen et al. (2018)
Collagenase modeli.p., 10 mg/kgRen et al. (2018)
Sepsis-associated encephalopathyCecal ligation puncture modeli.p., 10 mg/kgFu et al. (2018)
Cerebral ischemiaTransient middle cerebral artery occlusioni.p., 50 mg/kgFranke et al. (2020); Ismael et al. (2018a); Wang et al. (2019b)
Photothrombotic ischemiai.p., 50 mg/kgYe et al. (2017a)
Type 2 diabetes with a middle cerebral artery occlusioni.p., 50 mg/kgHong et al. (2018)
Subarachnoid hemorrhageEndovascular perforation processi.p., 10 mg/kgLi et al. (2020a); Luo et al. (2019)
EpilepsyPentylenetetrazole kindling modeli.p., 10 mg/kgShen et al. (2018)
Status epilepticus modeli.p., 50 mg/kgYue et al. (2020)
Acrylamide poisoningAcrylamide exposurei.p., 5 mg/kgSui et al. (2020b)
Opioid-induced neuroinflammationMorphine and fentanyl treatmenti.p., 5 mg/kgCarranza-Aguilar et al. (2020)
Chronic migraineRecurrent nitroglycerin stimulationi.p., 10 mg/kgHe et al. (2019)
Perioperative neurocognitive disordersLaparotomy under isoflurane anesthesiai.p., 10 mg/kgFu et al. (2020)
Isoflurane-exposed aged micei.p., 10 mg/kgFan et al. (2018)
Poststroke cognitive impairmentMurine model of photothrombotic strokei.p., 50 mg/kgLi et al. (2020e)
Post–cardiac arrest cognitive impairmentCardiac arrest and cardiopulmonary resuscitationi.p., 10 mg/kgChang et al. (2020); Jiang et al. (2020)
Social isolation–induced cognitive impairmentChronic social isolationi.p., 5 mg/kgNiu et al. (2020)
Anxiety and post-traumatic stress disorderMurine electric foot shocksi.p., 1 mg/kgDong et al. (2020)
LungSteroid-resistant asthmaChlamydia and Haemophilus respiratory infection–mediated, ovalbumin-induced, severe, steroid-resistant allergic airway disease modeli.p., 10 mg/kgKim et al. (2017)
HDM/Complete Freund's Adjuvant severe asthmai.p., <200 mg/kgPrimiano et al. (2016); Rossios et al. (2018)
Aspergillus fumigatus (Af)- and Alternaria alternata (Aa)-induced asthman/aJeong et al. (2018)
AsthmaToluene dissocynate modeli.p., 200 mg/kgChen et al. (2019a)
OVA-induced murine modeli.p., 20 mg/kgLv et al. (2018); Wang et al. (2018b)
IR lung injuryMicrovascular clampi.p., 50 mg/kgXu et al. (2018b)
ARDS/COPDLPS-induced lung inflammationi.p., 50 mg/kgWang et al. (2021)
Particulate matter–induced lung injuryPM2.5 inhalationi.v., 2 mg/kgJia et al. (2021)
Radiation pneumonitisIrradiationi.p., 10 mg/kgLi et al. (2020c)
Pulmonary hypertensionMonocrotaline-induced pulmonary hypertensioni.p., 10 mg/kgSun et al. (2021)
SarcoidosisTrehalose-6,6-dimycolate– granuloma mouse modeli.p., 10 mg/kgHuppertz et al. (2020)
Cystic fibrosisB6.129P2(CF/3)-Cftr TgH(neoim)Hgu micei.p., 50 mg/kgMcElvaney et al. (2019)
Allergic rhinitisOVA-induced murine modelIntranasal, 200/400 µgZhang et al. (2020)
HeartAtherosclerosisWestern-type diet-fed apoE−/− mice with atherosclerotic plaquesi.p., 10 mg/kgvan der Heijden et al. (2017)
TET2-deficient modelInfusion pump, 5g/kgFuster et al. (2017)
Heart failureTET2-deficient model of permanent ligation of the left anterior descending arteryInfusion pump, 5g/kgSano et al. (2018)
TET2-deficient model TAC modelInfusion pump, 5g/kgSano et al. (2018)
HypertensionAngiotension II–induced hypertensioni.p., 10 mg/kgGan et al. (2018)
Stress-induced hypertensionInfusion pump, 0.5 µmol/l finalHu et al. (2020)
Myocardial infarctionCoronary artery ligationi.p., 10 mg/kgGao et al. (2019); Li et al. (2020d)
Cardiac ischemia reperfusioni.p., 6 mg/kgvan Hout et al. (2017)
Atrial fibrillationCM-KI micei.p., 10 mg/kgYao et al. (2018)
Cardiac injury induced by metabolic dysfunctionHigh sugar and fat diet–induced obesityi.p., 20 mg/kgPavillard et al. (2017)
Heart failureGPER KOi.p., 10 mg/kgWang et al. (2019a)
Endothelial dysfunctionCigarette smoke exposure in ratn/aWang et al. (2019d)
Visfatin/eNampt-inducedi.p., 10 mg/kgRomacho et al. (2020)
GastrointestinalColitisMurine DSS-induced acute colitisi.p., 50 mg/kgWu et al. (2018); Umiker et al. (2019)
Rat DSS-induced acute colitisi.p., 10 mg/kgSaber and El-Kader (2020)
miR-223–deficient DSS colitis micei.p., 20 mg/kgNeudecker et al. (2017)
Winnie modeli.p., 40 mg/kgPerera et al. (2018)
LiverAcute liver failureD-GalN–induced ALFi.p., 50 mg/kgWang et al. (2018a)
Circadian regulation of immunityLPS/D-GalN hepatic-injury mouse modeli.p., dose n/aPourcet et al. (2018)
NASHfoz/foz Mice (overnutrition model)PO, 20 mg/kgMridha et al. (2017)
Methionine- and choline-deficient diet modelPO, 10 mg/kgMridha et al. (2017)
Cognitive dysfunction in diabetesMCAO-induced stroke in diabetic rati.v., 3 mg/kgWard et al. (2019)
IR liver injuryPig transplantation modeli.v., 3 mg/kgYu et al. (2018)
Idiosyncratic drug-induced liver injuryIcaraside II–induced liver injuryi.p., 50 mg/kgWang et al. (2020b)
Liver fibrosisS. japonicum cercariae infection through the abdominal skini.p., 10 mg/kgZhang et al. (2019c)
BDL modeli.p., 10 mg/kgFrissen et al. (2020); Qu et al. (2019)
Pancreas/kidneyDiabetic encephalopathyObese and type 2 diabetic db/db micei.p., 10 mg/kgZhai et al. (2018)
Diabetes-associated atherosclerosisStreptozotocin-induced diabetic apolipoprotein knockout (ApoE−/−) mouse modeli.p., 10 mg/kgSharma et al. (2021)
Insulin resistanceMaternal HFD-induced insulin resistancei.p., 10 mg/kgWada et al. (2020)
Islet transplantation rejectionIslet transplantation modeli.p., 25 mg/kgMatsuoka et al. (2020)
Chronic crystal nephropathyOxalate crystal-induced kidney fibrosisi.p., 200 mg/kgLudwig-Portugall et al. (2016)
Renal fibrosisMultiple-cisplatin-induced murine modeli.p., 20 mg/kgLi et al. (2019)
I/R kidney injuryKidney transplanti.p., 5 mg/kgZou et al. (2020)
Obesity-associated renal diseaseObesity-related glomerulopathy mouse modeli.p., 10 mg/kgZhao et al. (2019)
Renal hypertension1K/DOCA/salt-dependent hypertension in miceInfusion pump, 10 mg/kgKrishnan et al. (2016, 2018)
SkinPsoriasisImiquimod modelPO, <200 mg/kgPrimiano et al. (2016)
EyeRetinal neovascularisatonOxygen-induced ischemic retinopathyIntravitreal, 1 µl, < 1 mMSui et al. (2020a)
ReproductivePreterm birthLPS-induced intra-amniotic inflammationi.p., 50 mg/kgFaro et al. (2018)
SB100-induced amniotic inflammationi.p., 50 mg/kgGomez-Lopez et al. (2018)
Primary dysmenorrheaEstradiol- and oxytocin-induced murine modeli.p., 0.2 ml at 2 mg/mlTang et al. (2020)
ImmunityInnate immunityStem cell mobilization from bone-marrow modeli.p., 50 mg/kgLenkiewicz et al. (2019)
Innate to adaptive immunityHeat-induced sterile injury modeli.p., 20 mg/kgChakraborty et al. (2018)
Systemic lupus erythematosus–lupus nephritisLupus-prone micei.p., 10 mg/kgFu et al. (2017)
Multiple sclerosisMurine experimental autoimmune encephalomyelitisi.p., 20 mg/kgColl et al., (2015); Hou et al. (2020); Xu et al. (2020); Xu et al. (2018c)
InheritableMuckle-Wells syndromeMuckle-Wells mouse (NLRP3A350V)i.p., 20 mg/kgColl et al. (2015)
Rheumatoid arthritisCollagen-induced modeli.p., 10 mg/kgGuo et al. (2018)
Sickle cell diseaseHumanized sickle cell disease (SCD) micei.p., 50 mg/kgVogel et al. (2017)
VCP-associated diseaseVCPR155H/+ heterozygote micePO, 30 mg/kgNalbandian et al., (2017)
PainMultiple sclerosis–associated neuropathic painRelapsing-remitting experimental encephalomyelitisi.p., 50 mg/kgKhan et al. (2017)
Chronic prostatitis/chronic pelvic painExperimental autoimmune prostatitis (EAP) mouse modeli.p., 10 mg/kgZhang et al. (2019a)
Cancer-induced bone painWalker 256 cancer-induced bone pain rat modeli.p., 10 mg/kgChen et al. (2019b)
HyperalgesiaLPSi.p., 3 mg/kgDolunay et al. (2017)
CancerHuman squamous cell carcinoma of head and neck cancerTgfbr1/Pten 2cKO mousei.p., 10 mg/kgHuang et al. (2017)
Tgfbr1/Pten 2cKO mice (K14- Cretam; Tgfbr1flox/flox; Ptenflox/flox)i.p., 10 mg/kgChen et al. (2018c)
InfectionBacterialS. aureus infection modeli.p., 50 mg/kgCohen et al. (2018)
Influenza/MSSA superinfectionOropharyngeal aspiration, 5 mg/kgRobinson et al. (2018)
B. cereus infectioni.p., 50 mg/kgFox et al. (2020); Mathur et al. (2018)
Group A Streptococcusi.v., 20 mg/kgLaRock et al., (2016); Lin et al. (2019)
Murine cecal ligation and puncturei.p., 20 mg/kgKang et al. (2016); Luo et al. (2020)
Rat cecal ligation and puncturei.p., 50 mg/kgCornelius et al. (2020); Danielski et al. (2020)
ViralJuvenile mouse model of IAV infectioni.p., 10 mg/kgCoates et al. (2017)
IAV infectioni.p., 5 mg/kgTate et al. (2016)
IAV, lethal strain H7N9Intranasal, 5 mg/kgPinar et al. (2017)
Chikungunyai.p., 20 mg/kgChen et al. (2017c)
Ross river virusi.p., 20 mg/kgChen et al. (2017c)
ParasiticHelminth wormi.p., 20 mg/kgAlhallaf et al. (2018)
L. major and lymphocytic choriomeningitis virus Armstrong straini.p., 10 mg/kgNovais et al. (2017)
Experimental cerebral malariai.p., 50 mg/kgStrangward et al. (2018)
  • ALF, acute liver failure; HFD, high fat diet; I/R, ischemia reperfusion; McGill-R-Thy1-APP TG, transgenic rat expressing human APP751 with the Swedish and Indiana mutations Alzheimer model; MSSA, methicillin sensitive Staphylococcus aureus; n/a, not applicable; PFF, preformed fibral; PLB2TAU, PLB2TAU knock in; 1K/DOCA, uninephrectomized rat deoxycorticosterone model.