SGI-110

Research use only, not for human use.

A novel DNA hypomethylating dinucleotide that inhibits DNA methyltransferase (DNMT).

A novel DNA hypomethylating dinucleotide that inhibits DNA methyltransferase (DNMT); induces/up-regulates the expression of investigated cancer/testis antigens in broad cancer cell lines, both at mRNA and at protein levels; reduces the stem-like properties of ALDH(+) ovarian cancer stem-like cells, including their tumor-initiating capacity, resensitizes these OCSCs to platinum; induces hypomethylation and CTA gene expression in a dose dependent manner both in vitro and in vivo.Blood Cancer Phase 3 Clinical.

Exposure to Guadecitabine induces the expression of investigated cancer/testis antigens (CTA) in CTA-negative cancer cells.Results show that Guadecitabine induces and/or strongly up-regulates the constitutive levels of MAGE-A3- and NY-ESO-1-specific mRNA expression in neoplastic cells of all histotypes investigated. Exposure to Guadecitabine significantly (p<0.05) up-regulates the constitutive levels of expression of HLA class I antigens, HLA-A2 allospecificity, and of the co-stimulatory molecule ICAM-1, on Mel 275 melanoma cells.Results show that treatment with Guadecitabine induces a significant (p<0.01) reduction in the constitutive methylation levels of CTA promoters in investigated cancer cells. Mean values of the percentage of demethylation induced by Guadecitabine in MAGE-A1 and NY-ESO-1 promoters are 57 and 30 %, in Mel 195, and 22 and 33 % in MZ-1257 RCC cells, respectively.

Guadecitabine (S110) is effective at retarding tumor growth. While the tumors do not shrink in size with Guadecitabine treatment, they experience very minimal growth while the tumors treated with PBS only show substantial growth. In addition, Guadecitabine induces much less toxicity as determined by mouse weight changes when given subcutaneously (SQ) compare to that with IP injections.

SGI 110 | SGI110 | Guadecitabine

Chromatin/Epigenetic

DNMT

DNMT

Cancer

Blood cancer

929901-49-5

557.41

C18H24N9O10P

>98% (HPLC)

H2O

O=P(OC[C@@H]1O[C@@H](N2C=NC3=C2N=C(N)NC3=O)C[C@H]1O)(O[C@@H]4[C@@H](CO)O[C@@H](N5C(N=C(N)N=C5)=O)C4)O

(2R,3S,5R)-5-(4-amino-2-oxo-1,3,5-triazin-1(2H)-yl)-2-(hydroxymethyl)tetrahydrofuran-3-yl (((2S,3R,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl) hydrogen phosphate

(-20℃)

With Ice Pack

≥ 2 years