p53 is the guardian of the genome, mutated in almost every cancer, but p53 has been difficult to target. Alternative splicing of the TP53 gene and p53 isoforms provide a mechanism to rescue p53. Levels of an isoform of p53 called p53β can be directly increased by inhibiting SRSF3, a splicing factor. SFI003 is a small molecule tool compound that inhibits SRSF3 and has been shown to cause differentiation and suppression of the cancer phenotype in skin, colon, kidney, and the blood. We have synthesized three novel small molecules similar in efficacy to SFI003 (provisional composition of matter patent, October 2025); we have also crystallized SRSF3, determined the binding pocket, and have three other lead compound candidates. Blavatnik funds will be used to further test and validate these 6 compounds, comparing their effects with SFI003 on SRSF3, p53β, keratinocyte differentiation, and growth inhibition of cancer in vitro and in vivo.