(S)-Thalidomide

• CAT Number: R002607
• CAS Number: 841-67-8
• Molecular Formula: C13H10N2O4
• Molecular Weight: 258.23
• Purity: ≥95%
• Synonyms: 2-[(3S)-2,6-dioxopiperidin-3-yl]isoindole-1,3-dione
• InChI: InChI=1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)/t9-/m0/s1
• InChIKey: UEJJHQNACJXSKW-VIFPVBQESA-N
• SMILES: C1CC(=O)NC(=O)C1N2C(=O)C3=CC=CC=C3C2=O

(S)-Thalidomide ((S)-(-)-Thalidomide) is the S-enantiomer of Thalidomide. (S)-Thalidomide has immunomodulatory, anti-inflammatory, antiangiogenic and pro-apoptotic effects[1][2][3]. (S)-Thalidomide induces teratogenic effects by binding to cereblon (CRBN) [4].
(S)-Thalidomide treatment results in a reduction in cell viability in U266 cells with an IC50 of 362 μM[1].
(S)-Thalidomide treatment increased apoptosis in a dose-dependent manner in U266 cells[1].
There are changes in the expression profile of genes involved in angiogenesis and apoptosis, but the changes are most dramatic in the apoptotic genes. In particular, the expression of I-κB kinase is decreased by two-fold, which is associated with a four-fold decrease in NF-κB expression. (S)-Thalidomide increases the Bax:Bcl-2 ratio, also increases I-kB protein levels, and decreases NF-kB activity. A dramatic decrease in Bcl-2 expression with (S)-Thalidomide suggests a possible enhancement of cytotoxic effect if combined with other cytotoxic agents[1].
Thalidomide does cause limb reduction defects in chick embryos as long as the embryos are directly exposed to the drug. The most useful techniques are implanting Thalidomide-soaked beads into the embryo immediately adjacent to the limb territory or soaking presumptive chick limb territories in Thalidomide and then grafting the explants to a host embryo celom. Thalidomide affects the chick limb grafted to a host embryo in a dose response fashion. Furthermore, (S)-Thalidomide is more teratogenic than (R)-Thalidomide[1].

Reference

[1]. Liu WM, et al. s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line. Hematol J. 2004;5(3):247-54.
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[2]. Stephens TD. The effect of thalidomide in chicken embryos. Birth Defects Res A Clin Mol Teratol. 2009 Aug;85(8):725-31.
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[3]. Murphy S, et al. Enantioselectivity of thalidomide serum and tissue concentrations in a rat glioma model and effects of combination treatment with cisplatin and BCNU. J Pharm Pharmacol. 2007 Jan;59(1):105-14.
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[4]. Tokunaga E, et al. Understanding the Thalidomide Chirality in Biological Processes by the Self-disproportionation of Enantiomers. Sci Rep. 2018 Nov 20;8(1):17131.
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