Table 2.
Small molecule splicing modulators in cancer.
| Compound | Target of Inhibition | Mechanism(s) of Action | Reference | |
|---|---|---|---|---|
| Pladienolide: | SF3B complex | Interact with SF3B1 and promote conformational alteration | [10,116,117,118] | |
| Pladienolides A–G | Antitumor activities reported in human BSY-1, PC-3, OVCAR-3, DU-145, WiDr, HCT-116 cells, primary human colon cancer cells, xenograft mouse model, etc. | |||
| Pladienolide analog: | SF3B complex | Interacts with SF3B1 and promotes splicing alteration | [10,118,119,120] | |
| E7107 | Inhibition of tumor growth in human breast, ovary, non-small cell lung cancer, xenograft mouse model, etc. | |||
| Spliceostatin: | SF3B complex | Interface interaction of U2 snRNP with pre- | [10,118,121,122] | |
| FR901463 | ||||
| FR901464 | mRNA | |||
| FR901465 | ||||
| Meayamycin B | Antitumor activities reported in murine solid tumors (colon 38 and Meth A), human lung adenocarcinoma solid tumor (A549), human colorectal carcinoma (HCT-116), human prostate tumor (PC-3), human rhabdomyosarcoma (rh18), xenograft mouse model, etc. | |||
| Spliceostatin A | ||||
| Sudemycins | ||||
| Sufonamides: | RBM39 | Bind a receptor of the CRL4 E3 ubiquitin ligase complex (known as DCAF15), and direct ubiquitin-mediated degradation of RBM39 | [123,124,125] | |
| Indisulam | ||||
| Tasisulam | ||||
| E7820 | ||||
| SRPK inhibitor: | SRPK1 and SRPK2 | Competitively inhibit SRPK1 and SRPK2, subsequently affect SR protein phosphorylation | [126,127,128] | |
| SRPIN340 | ||||
| SRPKIN-1 | SRPIN340 is reported to block angiogenesis and related tumor growth in nude mice | |||
| SRPKIN-1 is reported to convert the proangiogenic VEGF isoform to the angiogenic isoform | ||||
| CLK inhibitor: | CLK1, CLK2, CLK4 | Competitively inhibit CLK1, CLK2, and CLK4, and subsequently affect SR protein phosphorylation | [10,129,130] | |
| T-025 | ||||
| TG003 | T-025 is reported to affect global alternative splicing, inducing cancer cell death, and inhibiting cancer cell growth | |||
| SRPK and CLK | SRPK1, SRPK2, CLK1, CLK2 | Inhibit SRPK1, SRPK2, CLK1, and CLK2, and subsequently affect SR protein phosphorylation | [10,118,131] | |
| inhibitor: | ||||
| Cpd-1 | ||||
| Cpd-2 | ||||
| Cpd-3 | ||||
| Topoisomerase I inhibitor: | Topoisomerase I | Inhibitory effect prior to step one of splicing | [132] | |
| NB-506 | Inhibits SRSF1 phosphorylation and splicing of Bcl-X, CD44, SRSF2, and Sty in P388 cultured cells | |||
| Amiloride | Unknown | Inhibits SRSF1 phosphorylation and splicing of Bcl-X, HIPK3, and RON/MISTR1 in Huh-7 cultured cells | [133] |