Table 3 Summary of the drug development status for the activation of MiT members

Rapamycin

Inhibitor of mTOR; autophagy activation; mitochondrial quality; control MiT activation

PD

Preclinical (in vitro and in vivo)

[186, 222]

Everolimus

Inhibitor of mTOR; immunosuppressant; inhibition of T-cell and B-cell proliferation

Immuno-suppression in heart transplant recipients

Clinical (pilot study)

[225]

Sirolimus and RTB101 (alone or in combination)

Inhibitors of mTOR; autophagy activation

PD; MSA

Clinical trial

anzctr.org.au (trial ID: ACTRN12619000372189), phase 1/2, trial information not updated; clinicaltrials.gov (trial ID: NCT03589976), phase 2, trial stopped

Dynasore

GTPase inhibitor targeting dynamin; TFE3 and TFEB activation

HD; PD

Preclinical (in vitro)

[227,228,229]

Trehalose

Naturally occurring sugar; TFEB activation

Tauopathy; PD

Preclinical (in vitro and in vivo)

[222, 230,231,232]

2-Hydroxypropyl-β-cyclodextrin (HPβCD)

Drug delivery vehicle; TFEB activation

cholesterol storage disorder (NPC)

Preclinical (in vitro); clinical trial

[235, 236]; clinicaltrials.gov (trial ID: NCT03893071), phase 1/2; clinicaltrials.gov (trial ID: NCT03893071), phase 2/3

Curcumin and its derivatives C1, C4

mTOR-independent TFEB activators

AD; PD

Preclinical (in vitro and in vivo)

[237, 239,240,241]

Celecoxib

Cyclooxygenase 2 inhibitor; TFEB activation

PD

Preclinical (in vitro)

[243]

Ibudilast

Anti-inflammatory phosphodiesterase inhibitor; TFEB activation

Preclinical (in vitro)

[244]

PP242

mTORC1 inhibitor; TFEB activation

PD

Preclinical (in vitro)

[245]

Ambroxol

GCase chaperone; TFEB activation

PD

Preclinical (in vivo); clinical trial

[246, 248, 249]; clinicaltrials.gov (trial ID: NCT02941822), phase 2 completed; clinicaltrials.gov (trial ID: NCT02914366), phase 2

Veliparib

PARP1 inhibitor; TFEB activation

PD

Preclinical (in vivo)

[220]

Trifluoperazine

Calmodulin and Dopamine receptor blockade; TFEB activation

PD

Preclinical (in vivo)

[210]