SGI-1027
SGI-1027 is an inhibitor of DNMT with IC50 values of 12.5μM, 8μM and 7.5μM, respectively for DNMT1, DNMT3A and DNMT3B [1].
SGI-1027 shows inhibition with mammalian DNMTs and bacterial M. SssI in vitro. Both the endogenous and recombinant DNMTs can be inhibited by SGI-1027. The mechanism of this inhibition is that SGI-1027 competes with Ado-Met but not the substrate DNA within the cofactor binding site of the enzyme. SGI-1027 inhibits DNA methylation through directly inhibiting DNMTs [1].
In cancer cells, many TSGs are silenced due to hypermethylation of CpG islands in their promoters. SGI-1027 can demethylates these CpG islands and reactivate the silenced TSGs. In RKO cells, prolonged treatment of SGI-1027 induces reexpression of P16 and TIMP3 genes. Moreover, SGI-1027 is found to cause selective degradation of DNMT1 via proteasomal pathway [1].
References:
[1] Datta J, Ghoshal K, Denny WA, Gamage SA, Brooke DG, Phiasivongsa P, Redkar S, Jacob ST. A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Cancer Res. 2009 May 15;69(10):4277-85.
- 1. Schwartz, Hannah, et al. "In vitro Methods to Better Evaluate Drug Responses in Cancer." UMass Chan Medical School. September 8, 2022.
- 2. Ryan Richards, Megan E. Honeywell, et al. "FLICK: an optimized plate reader-based assay to infer cell death kinetics." STAR Protoc. 2021 Feb 3;2(1):100327. PMID: 33659903
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 461.52 |
| Cas No. | 1020149-73-8 |
| Formula | C27H23N7O |
| Solubility | ≥22.25 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH |
| Chemical Name | N-[4-[(2-amino-6-methylpyrimidin-4-yl)amino]phenyl]-4-(quinolin-4-ylamino)benzamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC(=NC(=N1)N)NC2=CC=C(C=C2)NC(=O)C3=CC=C(C=C3)NC4=CC=NC5=CC=CC=C54 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Description | SGI-1027 is an inhibitor of DNMT with IC50 values of 6, 8, 7.5 μM for DNMT1, DNMT3A, and DNMT3B, respectively | |||||
| Targets | DNMT1 | DNMT3B | DNMT3A | |||
| IC50 | 6 μM | 7.5 μM | 8 μM | |||
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