Sulfopin

• CAS: 2451481-08-4
• Catalog Number: ACM2451481084
• Category: Inhibitors
• Molecular Weight: 281.80
• Molecular Formula: C11H20ClNO3S
• Description: Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo. Sulfopin is highly selective, as validated by two independent chemoproteomics methods, achieves potent cellular and in vivo target engagement and phenocopies Pin1 genetic knockout. Sulfopin induced downregulation of c-Myc target genes, reduced tumor progression and conferred survival benefit in murine and zebrafish models of MYCN-driven neuroblastoma, and in a murine model of pancreatic cancer. Sulfopin is a chemical probe suitable for assessment of Pin1-dependent pharmacology in cells and in vivo, and that Pin1 warrants further investigation as a potential cancer drug target.
• IUPAC Name: 2-chloro-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-neopentylacetamide
• Canonical SMILES: O=C(N(CC(C)(C)C)C(CC1)CS1(=O)=O)CCl
• InChI: InChI=1S/C11H20ClNO3S/c1-11(2,3)8-13(10(14)6-12)9-4-5-17(15,16)7-9/h9H,4-8H2,1-3H3
• InChI Key: NMHVAHHYKGXBMY-UHFFFAOYSA-N
• Solubility: To be determined
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: Sulfopin (PIN1-3) is a highly selective covalent inhibitor of Pin1 with an apparent Ki of 17 nM.
• Drug Formulation: To be determined
• Elemental Analysis: C, 46.89; H, 7.15; Cl, 12.58; N, 4.97; O, 17.03; S, 11.38
• Exact Mass: 281.0852
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To test whether Sulfopin affects Myc transcriptional output, Mino B cells were treated with either Sulfopin (1 μM, 6 h, in triplicate) or DMSO and performed a global RNA-seq analysis to detect differentially expressed genes: 206 genes were found to be significantly downregulated. Enrichr analysis of these transcripts, to identify transcription factors coordinating this response41, identified Myc target genes as the first and third most enriched sets in K562 and HeLa-S3 cells (adjusted P = 1.99 × 10-16 and 2.00 × 10-13, respectively), suggesting that Sulfopin downregulates Myc's transcriptional signature. This finding matches the reported transcriptional effects of BJP-06-005-3 in PATU-8988T cells27. To further validate the effect of Sulfopin on Myc transcriptional activity, HEK293 cells were cotransfected with a Myc reporter construct (4× E-box luciferase) and Pin1. As expected, Pin1 expression increased Myc transcriptional activity while treatment with 2 μM Sulfopin for 48 h resulted in a significant reduction in relative luciferase activity. These results suggest that treatment with Sulfopin downregulates Myc target genes, making Myc-driven cancers natural candidates for its therapeutic application.; Reference: Nat Chem Biol. 2021 Sep;17(9):954-963. https://pubmed.ncbi.nlm.nih.gov/33972797/
• In Vivo Activity: The effects of Sulfopin were assessed in a murine model of neuroblastoma, Th-MYCN genetically engineered mice, in which human MYCN is expressed under the tyrosine hydroxylase promoter. Once tumors had become palpable, mice were randomly assigned to treatment groups and treated once (QD) or twice (BID) per day with either vehicle or 40 mg kg-1 Sulfopin. Tumor sizes were monitored over 7 days of treatment via magnetic resonance imaging (MRI). With the exception of one mouse, all tumors treated BID showed significant reduction in size, two of which showed near complete response. Sulfopin-treated QD mice showed a significant (P = 0.0127) average increase in survival of 10 days, while Sulfopin-treated BID mice showed an even more pronounced (P = 0.0049) average increase of 28 days. It is noted that mice in the BID arm received only 56 doses of compound (dose license limit).; Reference: Nat Chem Biol. 2021 Sep;17(9):954-963. https://pubmed.ncbi.nlm.nih.gov/33972797/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).