Table 2 The effects of various HMGB1 inhibitors

HMGB1-neutralizing antibody

In vitro

Inhibits HMGB1-induced autophagy and increases the sensitivity of leukemia cells to chemotherapy

[175]

mAb (2G7)

In vivo

Improves arthritis, LN and drug-induced liver injury

[176,177,178]

s-RAGE

In vivo

Blocks the HMGB1-RAGE signaling pathway

[179]

HMGB1 A-box

In vitro

Inhibits the proinflammatory actions of the B-box

[5]

TAT-HMGB1A

In vitro

Reduces secretion of endogenous HMGB1 protein

[180]

GL

In vitro, in vivo

Suppresses HMGB1 phosphorylation and secretion via PKC/CaMKIV

[181]

EP

In vitro, in vivo

Inhibits HMGB1 secretion by inducing HO-1 via PI3k/Akt and Nrf2 pathways; reverses the HMGB1-induced senescent phenotype of BM-MSCs; reduces RAGE expression and NF-κB/STAT3 pathway activation

[93, 184, 185]

quercetin

In vitro

Promotes apoptosis by attenuating the expression of HMGB1 and RAGE and suppressing the activation of NF-κB

[186]

ICM

In vitro

Inhibits HMGB1 nucleoplasmic translocation and autophagy by enhancing the interaction between Beclin-1 and E3 ubiquitin ligase RNF216

[187]

sLPC

In vivo

Suppresses HMGB1 phosphorylation and extracellular release

[188]

P5779

In vitro, in vivo

Interrupts disulfide-HMGB1/MD-2 binding; suppresses HMGB1-induced TNF release

[189]

rTM

In vitro, in vivo

Decreases serum HMGB1 levels and improves SIRS in hematological malignancies; improves DIC in AML; inhibits HMGB1 protein secretion and inhibits I-κB phosphorylation

[190,191,192]