TABLE 1.

Small-molecule compounds for inhibiting autophagy in cancer therapy.

Target	Compound	Mechanism	Cancer	Biological activity	Ref.
ULK1/2 inhibitor	SBI-0206965	Inhibiting cytoprotective autophagy and promote apoptosis by destabilizing the pro-survival proteins Bcl-2/Bcl-xl	Lung cancer/triple-negative breast cancer	ULK1 IC50 = 108 nM	Xiang et al. (2020)
				ULK2 IC50 = 711 nM
	MRT67307	Blocking ATG through targeting ULK1	Cancer	ULK1 IC50 = 45 nM	Chan, (2009)
				ULK2 IC50 = 38 nM
	MRT68921	Inhibiting autophagy by reducing the transformation of LC3-I to LC3-II	High-grade serous ovarian cancer	ULK1 IC50 = 2.9 nM	Ren et al. (2020)
				ULK2 IC50 = 1.1 nM
	SBP-7455	Inhibiting autophagy by targeting ULK1	Triple-negative breast cancer	IC50 = 13 nM	Tang et al. (2017)
	ULK-101	Inhibiting autophagy by targeting ULK1	Lung cancer	ULK1 IC50 = 8.3 nM	Petherick et al. (2015)
				ULK2 IC50 = 30 nM
				EC = 390 nM
	ULK-100	Inhibiting autophagy by targeting ULK1	Lung cancer	ULK1 IC50 = 1.6 nM	Petherick et al. (2015)
				ULK2 IC50 = 2.6 nM
				EC = 83 nM
	SR-17398	Inhibiting autophagy by targeting ULK1	Lung cancer	IC50 = 22.4 μM	Singha et al. (2020)
Non-selective PI3K Inhibitor	Wortmannin	Inhibiting autophagy by targeting PI3K	Colon cancer	IC50 = 20 nM	Zhang et al. (2020)
	3-Methyladenine	Inhibiting hypoxia-induced autophagy and increasing hypoxia-induced cell apoptosis	Cancer	IC50 = 60 μM	Ihle et al. (2004)
	LY294002	Inhibiting autophagy, inducing apoptosis and cell cycle arrest	Pancreatic cancer	IC50 = 0.5 μM	Wu et al. (2010), Wong et al. (2017), Dai et al. (2019), Andreidesz et al. (2021)
VPS34 inhibitor	SAR-405	Impeding autophagy through preventing autophagy vesicle trafficking	Renal tumor	IC50 = 1.2 nM	Yang and Klionsky (2010), Ohashi et al. (2019)
				KD = 1.5 nM
	Compound 31	Inhibiting autophagy by targeting VPS34	Solid tumors	VPS34 IC50 = 2 nM	Pasquier, (2015)
				PI3Kα, β, δ, γ IC50 > 2 µM mTOR IC50 > 10 µM
	VPS34-IN1	Impairing vesicular trafficking and mTORC1 signaling/inhibiting STAT5 phosphorylation downstream of FLT3-ITD signaling by targeting VPS34	Acute myeloid leukemia	IC50 = 1.2 Nm	Ronan et al. (2014), Pasquier et al. (2015)
				KD = 1.5 nM
	Spautin-1	Activating GSK3β-induced apoptosis via inactivating PI3K/AKT pathway/suppressing melanoma growth via ROS-mediated DNA damage	Chronic myeloid leukemia/melanoma	IC50 = 0.45–1.03 μM	Bago et al. (2014), Shao et al. (2014), Meunier et al. (2020)
	PIK-III	Enhancing VPS34-dependence in cancer cells by impairing iron mobilization via the VPS34–RAB7A axis	Chronic myeloid leukemia	VPS34 IC50 = 18 nM mTOR IC50 > 9.1 μM	Liu et al. (2011), Guo et al. (2020)
	SB02024	Potentiating cytotoxicity of Sunitinib and Erlotinib in breast cancer cell/inducing an infiltration of NK, CD8+, and CD4+ T cells in melanoma and colorectal cancer	Breast cancer/colorectal cancer/melanoma	Kd = 4.5 μM	Dowdle et al. (2014), Kobylarz et al. (2020)
	Autophinib	Suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway	Cancer	IC50 = 19 nM	Dyczynski et al. (2018)
ATG4B inhibitor	S130	Attenuating the delipidation of LC3 through targeting ATG4B to inhibit autophagy via PI3K/mTOR pathway	Colorectal cancer	IC50 = 3.24 µM	Nakatogawa et al. 2012)
				Kd = 4.0 µM
	NSC185058	Attenuating the delipidation of LC3 through targeting ATG4B to inhibit autophagy	Osteosarcoma/breast cancer	IC50 = 51 µM	Bortnik et al. (2020)
	FMK-9a	Regulating cell autophagy through PI3K activation	Cervical cancer/glioblastoma	IC50 = 260 nM	Akin et al. (2014), Fu et al. (2019)
				Kd = 3.89 µM
	UAMC-2526	Slowing down tumor growth and potentiating the effect of classical chemotherapy	Colorectal cancer	Plasma half-life = 126 min 70% metabolization after 30 min	Kurdi et al. (2017), Chu et al. (2018)
	Tioconazole	Suppressing autophagy and sensitizing cancer cells to chemotherapy	Breast cancer	ATG4A IC50 = 1.3 µM	Tanc et al. (2019)
				ATG4B IC50 = 1.8 µM