Table 2.

Compounds targeting MPQC players in cancer.

Type of Compounds	Drug Name	Target	Mechanisms of Action	Cancer Types	Stage of Drug Development	References
Inhibitors of cytosolic chaperones	DMAG	HSP90	Inhibits HSP90 by competing for ATP binding site and prevents chaperone role	Leukemia, melanoma, breast and ovarian cancers, medulloblastoma, cervical cancer, multiple myeloma, lung cancer	Clinical trials completed	[271,272]
	PES	HSP70	Inhibits HSP70 by acting on its C terminal binding domain, prevents substrate binding, and induces ROS	Lymphoma	Preclinic studies	[273,274]
	Gamitrinibs	HSP90	Binds HSP90 that accumulates at mitochondria and allows for cytochrome c release	Prostate	Completed	[275]
	Nab-paclitaxel	Microtubules	Binds to and stabilizes microtubules, preventing their depolymerization thus inhibiting cellular motility, mitosis, and replication	Non-small lung cell carcinoma	Active, not recruiting, phase 2	[276]
Inhibitors of mitochondrial proteins	Carboplatin	HSP40, DNA	Possible connection with HSP40; used in combinations with other drugs; induces intra-strand and inter-strand DNA cross-links, as well as DNA-protein cross-links. These carboplatin-induced DNA and protein effects result in apoptosis and cell growth inhibition	Non-small lung cell carcinoma, esophageal adenocarcinoma	Active, not recruiting, phase 2	[277,278,279,280,281] NCT02716038; NCT02998268
	ONC201/ONC212 (derivative of ONC201)	CLPP	Hyperactivates CLPP, which leads to protein synthesis inhibition and growth inhibition, or apoptosis via tumor-necrosis-factor-alpha-related apoptosis ligand	AML, gliomas, cervical, breast, endometrial, myeloma, lymphoma, endocrine, solid tumors	Completed (solid tumors), ongoing testing in phase 1 to phase 3	[204,282]
	AppCCl2P (metabolite of clodronate)	ANT	Inhibits ANT (adenine nucleotide transporter), mitochondrial oxygen consumption, and depolarizes mitochondrial membrane, all leading to apoptosis	Breast, bone, prostate, neoplasm	Phase 3, completed	[283,284,285]
	Chlorambucil	mtDNA	Chlorambucil with cisplatin attacks cisplatin-resistant cancer cells, alkylates mtDNA, induces apoptosis through mtDNA damage and mitochondrial metabolic pathways by reducing dependency on glucose, depolarizes mitochondrial membrane, and mtDNA alkylation-induced ROS	Prostate, breast	Completed	[286,287,288]
Targeting mitophagy	LCL-461, liensinine, chloroquine, and hydroxychloroquine, mito-metformin, mito-carboxyl-proxyl-nitroxide		Prevents fusion of autophagosomes with lysosomes and incurs damage to promote apoptosis	Glioma, multiple myeloma, melanoma, lung, pancreatic cancer, sarcoma	Completed	[270,289]
Mitochondria-targeting molecules	Derivatives of TPP	N/A *	Functions as a mitochondrial targeting signal	N/A	N/A	[277]
	Szeto–Schiller peptides—dimethyltyrosine	N/A	Targets molecules to IMM and reduces ROS via its residues	N/A	N/A	[281,283,290]
	Pyridinium-substituted tetraphenylethylene	N/A	Targets IMM, increases ROS, and disrupts membrane potential	N/A	N/A	[286,287,288]
	Indolinium-based compounds	N/A	Increases ROS and depolarizes membrane potential	N/A	N/A	[289,291]

* N/A, not applicable.