Table 1.
Drug candidates targeting HMGB1 or its upstream/downstream molecules for prevention of CIPN.
| Chemicals (Alternative Name) | Structure | Mechanisms of Action | Ref. | Prevention of CIPN (Administration Route; Animal; Anticancer Drug) |
Ref. |
|---|---|---|---|---|---|
| HMGB1-nAb | IgG (MW 150,000) | Binding to and inactivation of HMGB1 | [21,22] | Yes (i.p.; rat; PCT, VCR) Yes (i.p.; mouse; PCT) Yes (i.p.; mouse; OHP) |
[8] [9] [10] |
| TMα | Protein (MW 64,000) | Binding to HMGB1 and promotion of degradation of HMGB1 by thrombin | [18,35,36,89] | Yes (i.p.; rat; PCT, VCR) Yes (i.p.; mouse; PCT) Yes (i.p., mouse; OHP) Yes (i.v.; rat; OHP) Yes (i.v.; human; OHP) |
[8] [9] [10] [101] [37] |
| Glycyrrhizin (glycyrrhizic acid) | Small molecule (MW 822.9) |
Binding to both box A and box B of HMGB1 | [104] | N.D. | |
| Methotrexate | Small molecule (MW 454.44) |
Binding to HMGB1 and inhibition of HMGB1/RAGE interaction | [111] | N.D. | |
| Metformin | Small molecule (MW 129.16) |
Binding to the C-terminal acidic tail of HMGB1 | [112] | Yes (i.p.; rat; OHP) Yes (i.p.; mouse; CDDP) |
[116] [115] |
| EGCG | A green tea component, small molecule (MW 458.37) | Binding to HMGB1 and induction of aggregation of HMGB1 | [119] | N.D. | |
| Salicylic acid | Aspirin metabolite, small molecule (MW 138.12) |
Bonding to box A and box B of HMGB1 | [120] | N.D. | |
| FPS-ZM1 | Small molecule (MW 327.8) |
Blockade of RAGE | [67,121] | Yes (i.p.; mouse; PCT) Yes (i.p.; mouse; OHP) |
[9] [10] |
| LMWH (parnaparin) | (MW 4500~6500) | Blockade of RAGE | [122,123] | Yes (i.p.; mouse; PCT) Yes (i.p.; mouse; OHP) |
[9] [10] |
| Azeliragon (PF-04494700 or TTP488) | Small molecule (MW 532.1) |
Blockade of RAGE | [67,124,125,126] | N.D. | |
| LPS-RS | LPS from the photosynthetic bacterium Rhodobacter sphaeroides | Blockade of TLR4 | [127,139] | Yes (i.t.; rat; PCT) No (i.p.; mouse; PCT) Yes (i.p.; mouse; OHP) |
[95] [9] [10] |
| Eritoran (E5564) | Synthetic lipid A analogue (MW 1313.7) | Blockade of TLR4 | [127,131] | N.D. | |
| FP7 | Synthetic monosaccharide lipid A mimetic with about half MW of eritoran | Blockade of TLR4 | [132,133] | N.D. | |
| TAK-242 (CLI-095) |
Small molecule (MW 361.82) |
Blockade of TLR4 | [134,135] | Yes (i.v.; rat; PCT) Yes (i.p.; mouse *; PCT) No (i.p.; mouse **; PCT) Yes (i.p.; mouse, OHP) |
[94] [9] [9] [10] |
| AMD3100 (plerixafor) | Small bicyclam molecule (MW 129.16) | Blockade of CXCR4 | [136] | Yes (i.p.; mouse; PCT) Yes (i.p.; mouse; OHP) |
[9] [10] |
| Ethyl pyruvate | Stable lipophilic pyruvate derivative, small molecule (MW 116.11) |
Inhibition of HMGB1 secretion from macrophage | [137] | Yes (i.p.; mouse; PCT) No (i.p.; mouse; OHP) |
[9] [10] |
| Minocycline | Small molecule (MW 457.48) |
Inhibition of macrophage/microglia | [138] | Yes (i.p.; mouse; PCT) No (i.p.; mouse; OHP) |
[9] [10] |
| NAC | Small molecule (MW 163.20) |
Anti-oxidation, suppression of HMGB1 release | [9,55] | Yes (i.p.; mouse; PCT) | [9] |
Ref., References; *, C57BL/6 strain; **, ddY strain; N.D., not determined; PCT, paclitaxel; VCR, vincristine; OHP, oxaliplatin; CDDP, cisplatin; HMGB1-nAb, anti-HMGB1-neutralizing antibody; EGCG, (-)-epigalocatechin-3-gallate; LMWH, low molecular weight heparin; LPS-RS, lipopolysaccharide from Rhodobacter sphaeroides; NAC, N-acetylcysteine.