SGI-1027, DNMT Inhibitor

SGI-1027 is a potent DNMT inhibitor, which reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Treatment of different cancer cell lines with SGI-1027 resulted in selective degradation of DNMT1 with minimal or no effects on DNMT3A and DNMT3B. At a concentration of 2.5 to 5 micromol/L (similar to that of decitabine), complete degradation of DNMT1 protein was achieved within 24 h without significantly affecting its mRNA level. SGI-1027 may have the potential for use in epigenetic cancer therapy.

Product information

CAS Number: 1020149-73-8

Molecular Weight: 461.52

Formula: C27H23N7O

Chemical Name: N-(4-((2-amino-6-methylpyrimidin-4-yl)amino)phenyl)-4-(quinolin-4-ylamino)benzamide

Smiles: CC1=CC(NC2C=CC(=CC=2)NC(=O)C2C=CC(=CC=2)NC2=CC=NC3=CC=CC=C23)=NC(N)=N1

InChiKey: QSYLKMKIVWJAAK-UHFFFAOYSA-N

InChi: InChI=1S/C27H23N7O/c1-17-16-25(34-27(28)30-17)32-20-10-12-21(13-11-20)33-26(35)18-6-8-19(9-7-18)31-24-14-15-29-23-5-3-2-4-22(23)24/h2-16H,1H3,(H,29,31)(H,33,35)(H3,28,30,32,34)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

SGI-1027 was used at 10-300 µM final concentration in various in vitro assays.

References:

1. Datta J, et al. A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. (2009) Cancer Res. 69(10):4277-85.
2. García-Domínguez P, et al. Synthetic approaches to DNMT inhibitor SGI-1027 and effects on the U937 leukemia cell line. (2013) Bioorg Med Chem Lett. 23(6):1631-5.
3. Yoo J, et al. Molecular modeling studies of the novel inhibitors of DNA methyltransferases SGI-1027 and CBC12: implications for the mechanism of inhibition of DNMTs. (2013) PLoS One. 8(4):e62152.
4. Gamage SA, et al. Structure-activity relationships for 4-anilinoquinoline derivatives as inhibitors of the DNA methyltransferase enzyme DNMT1. (2013) Bioorg Med Chem. 21(11):3147-53.

Products are for research use only. Not for human use.