Table 1.
List of small molecules together with representative IDs of clinical trials and used in in vitro screening.
| Host Protein | Compound Targeting the Host Protein | Mechanism of Action of the Compound with Relevant Reference | Examples of Clinical Trials | TNFa Production Inhibition 4/24 h Post-LPS Treatment in RAW 264.7 Cell Line (IC50 Values µM) |
|---|---|---|---|---|
| MEK1/2 | AZD6244 | non-ATP-competitive MEK1/2 kinase inhibitor [22] | NCT01635023 | 0.44/0.33 |
| ERK1/2 | SCH772984 | selective and ATP competitive inhibitor of ERK1/2 [23] | NCT01358331 | 0.92/0.44 |
| HDAC1/3 | MS-275 | Inhibitor of histone deacetylases (HDACs); induces autophagy and apoptosis in cancer cell lines [24] | NCT01594398 | NA/1.54 |
| SIRT1 | EX-527 | Potently inhibitory effect against SIRT1 HDAC activity [25] | NCT04184323 | NA/NA |
| DOTL1 | EPZ5676 | an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L [26] | NCT02141828 | NA/NA |
| EZH2 | EPZ6438 | a potent, and selective of protein methyltransferase EZH2 inhibitor [27] | NCT02860286 | NA/NA |
| KDM1A | ORY-1001 | an orally active and selective lysine-specific demethylase KDM1A inhibitor [28] | 2018-000482-36 | NA/NA |
| BRD2 | RVX-208 | a potent BET bromodomain inhibitor for BD2, with 170-fold selectivity over BD1 [29] | NCT01423188 | NA/1.56 |
| BRD2/3/4 | OTX015 | a potent BET bromodomain inhibitor targeting BRD2, BRD3, and BRD4 proteins. Inhibits the expression of nuclear receptor binding SET domain protein 3 (NSD3) target genes [30] | NCT01713582 | 0.33/0.31 |
| BRD4 | (+)-JQ1 | a BET bromodomain inhibitor, targeting BRD4(1/2), binding to all bromodomains of the BET family, but not to bromodomains outside the BET family [31] | Not in trials; stability issues in vivo | 0.07/0.08 |
NA—not available.