Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo. Sulfopin is selective and enables efficient cellular and in vivo target engagement and phenotypic Pin1 knockout, validated by two independent chemical proteomic approaches. In mouse and zebrafish models of MYCN-driven neuroblastoma and mouse models of pancreatic cancer, Sulfopin induces downregulation of c-Myc target genes, reducing tumor progression and conferring survival benefits. Sulfopin is a chemical probe suitable for assessing Pin1-dependent pharmacology in cells and in vivo, and Pin1 deserves further investigation as a potential cancer drug target.

Physicochemical Properties

Molecular Formula	C11H20CLNO3S
Molecular Weight	281.799401283264
Exact Mass	281.09
Elemental Analysis	C, 46.89; H, 7.15; Cl, 12.58; N, 4.97; O, 17.03; S, 11.38
CAS #	2451481-08-4
PubChem CID	155804394
Appearance	White to off-white solid powder
LogP	1.6
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	17
Complexity	381
Defined Atom Stereocenter Count	0
InChi Key	NMHVAHHYKGXBMY-UHFFFAOYSA-N
InChi Code	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
Chemical Name	2-chloro-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-neopentylacetamide
Synonyms	Sulfopin;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	The MDA-MB-468 cells responded to SuLfopin (1, 2.5 μM; 4–8 days) with the greatest body weight [1]. Myc is neatly packaged by SuLfopin (2 μM, HEK293 cells; 48 hours) [1]. 1, 2.5 μM; PATU-8988T cells; 4 days) revealed a commensurate rise in cells in the growth 1 (G1) phase and a minor but noteworthy reduction in the number of cells in the synthesis (S) phase [1].
ln Vivo	SuLfopin (40 mg/kg; po; QD/BID for 7 days) induces regression of neuroblastoma in mice [1]. SuLfopin (20-40 mg/kg; ip; daily for 27 days) induces regression of neuroblastoma in mice. SuLfopin (25-100 μM) induces neuroblastoma outbreak in zebrafish [1].
Cell Assay	Cell Proliferation Assay[1] Cell Types: Kuramochi, MDA-MB-468, NGP, NBL-S, MDA-MB-468 Cell Tested Concentrations: 1, 2.5 μM Incubation Duration: 4, 6, 8 days Experimental Results: Display of different cancer cells There were differences in the antiproliferative effects of the lines Kuramochi, MDA-MB-468, NGP and NBL-S, with the most pronounced sensitivity observed in MDA-MB-468 cells.
Animal Protocol	Animal/Disease Models: transgenic Th-MYCN mice [1] Doses: 40 mg/kg Route of Administration: one time/day (QD). ) or twice (two times) daily (BID) for 7 days. Experimental Results: The average survival time of Sulfopin-treated QD mice was Dramatically increased by 10 days, while the average survival time of Sulfopin-treated BID mice was Dramatically increased by 28 days.
References	[1]. Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo. Nat Chem Biol. 2021;17(9):954-963.
Additional Infomation	Sulfopin is a sulfone that is thiolane substituted by two oxo groups at position 1 and by a (chloroacetyl)(2,2-dimethylpropyl)amino group at position 3. It is a covalent inhibitor of Pin1 (Ki = 17 nM) that inhibits Myc-driven tumors in vivo. It has a role as an EC 5.2.* (cis-trans-isomerase) inhibitor and an antineoplastic agent. It is a member of tetrahydrothiophenes, a sulfone, an organochlorine compound and a tertiary carboxamide.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~354.86 mM) H2O : ~4.35 mg/mL (~15.44 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5486 mL	17.7431 mL	35.4862 mL
	5 mM	0.7097 mL	3.5486 mL	7.0972 mL
	10 mM	0.3549 mL	1.7743 mL	3.5486 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.