Skip to main content

Table 1 Necroptosis-inducing anti-leukemia agents

From: Bypassing drug resistance by triggering necroptosis: recent advances in mechanisms and its therapeutic exploitation in leukemia

Disease

Agents

Targets

Mechanisms of necroptosis

Ref

AML

Birinapant+Emricasan

cIAPs, caspase-8

TNFR1 signaling; RIPK1/RIPK3/MLKL dependent

[123]

BV6+zVAD-fmk

cIAPs, pan-caspase

RIPK1/RIPK3/MLKL dependent; autocrine TNF-α

[124]

BV6+Cytarabine

cIAPs, DNA synthesis

RIPK1/RIPK3/MLKL dependent; autocrine TNF-α

[125]

BV6+Azacitidine or Decitabine

cIAPs, DNA methylation

RIPK1/RIPK3/MLKL dependent; autocrine TNF-α

[126]

BV6+MS275 or SAHA

cIAPs, Histone deacetylase

RIPK1/RIPK3/MLKL dependent; autocrine TNF-α

[127]

HXR9

HOX/PBX dimer

RIPK1 dependent

[133]

Diphtheria toxin GM-CSF

Protein synthesis

RIPK1 dependent

[137]

Erastin

Unknown

RIPK3 dependent; c-JNK and p38 dependent

[138]

ALL

BV6+Dexamethasone

cIAPs, Glucocorticoid receptor

RIPK1/RIPK3/MLKL activation; Bak activation and mitochondrial perturbation

[143]

BV6, LCL161, Birinapant

cIAPs

RIPK1/RIPK3/MLKL dependent; autocrine TNF-α; enhanced by hyperosmotic stress

[145]

BV6 + Azacytidine

cIAPs, DNA methylation

RIPK1/RIPK3/MLKL-dependent; autocrine TNF-α

[145]

Obatoclax

Bcl-2

Autophagy-dependent; mediated by RIPK1, CYLD

[149, 151]

MG132, Bortezomib

Proteasome

RIPK3/MLKL dependent; accumulation of polyubiquitinated RIPK3

[154]

CLL

Ethacrynic acid

LEF1

CYLD activation

[159, 160]

CML

LQFM018

Unknown

TNFR1 and CYLD upregulation; involvement of dopamine D4 receptor

[165]

Pig7

Lysosomal

MLKL activation; alteration of MMP and ROS levels

[167]