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Table 2 Small molecules and/or agents for inhibition of autophagy in the context of AML treatment

From: The dual role of autophagy in acute myeloid leukemia

Agents

Known for

Mechanism

Outcome/effects

Study model

Ref

Bafilomycin A1

Inhibitor of vacuolar H+-ATPase

Inhibition of autophagy accumulates the damaged mitochondria

Effective cytotoxicity in hypoxic condition

HL-60, MOLM-13, AML patients samples

[194]

Hydroxy-chloroquine

Anti-malarial drug

Inhibition of autophagy activates caspase 9 in Ara-C-resistant AML cells

Inducing intrinsic mitochondria apoptosis

U937, OCI-AMLM-2, AML patients samples

[192]

  

Inhibition of autophagy converted CD34( +)/ROSlow AML cells to CD34( +)/ROShigh AML cells

Increasing ROS production and inducing apoptosis

HL-60, K562, THP1, OCIM3, MOLM13, NB4, AML patients samples

[119]

SAR405

VPS34 inhibitor

SAR405 inhibits the autophagy process in FLT3-ITD AML cells

Inhibition of proliferation and Inducing apoptosis

MV4-11, MOLM-14, OCI-AML3, AML patients samples

[199]

   

Impairment of proliferation

MV4-11, MOLM-14, OCI-AML3, AML patients samples

[93]

THZ-P1-2

PI5P4K inhibitor

Lysosomal–autophagosomal defect and increased TFEB activation (mechanism studied in HeLa cells)

Anti-proliferative

THP1, OCI/AML-2, SKM1

[209]

VPS34-IN1

VPS34 inhibitor

Reduction of intracellular vesicle trafficking, inhibition of basal and L-asparaginase-induced autophagy, modulation of mTORC1 and FLT3-ITD signaling

Mitochondrial apoptotic cell death/Anti-leukemic

HL-60, MOLM-14, several AML cell lines

[211]

XRK3F2

Inhibitor of ZZ domain of p62

Inhibition the binding of p62 with defective mitochondria to block mitophagy

Inhibition of leukemia-initiating potential of leukemia cells

K562, HL-60, patient-derived tumor xenograft model

[212]

Chidamide

HDAC inhibitor

Inhibition of SIRT1 expression to inhibit the Ara-C or sorafenib-induced autophagy

Enhancement of cytotoxicity of chemotherapy drugs

THP-1, MV4-11

[214]

TAK-165

HER2 inhibitor

HER2-independet inhibition of autophagy, but induction of chaperone-mediated autophagy (CMA) during TAK-165/AC220 combinatorial treatment

Enhanced efficacy of AC220 to induce cancer cell death

HEL, ES-2, OCI-AML3

[215]

  1. Ara-C cytarabine, CD34 cluster of differentiation 34, ROS reactive oxygen species, VPS34 vacuolar protein sorting 34, FLT3-ITD fms-like tyrosine kinase 3-Internal tandem duplications, PI4P4K phosphatidylinositol 5-phosphate 4-kinases, TFEB transcriptional factor EB, HDAC histone deacetylases, HER2 human epidermal growth factor receptor 2, AC220 FLT3 receptor tyrosine kinase inhibitor