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Chemical Structure| 1561178-17-3 Chemical Structure| 1561178-17-3

Structure of SGC0946
CAS No.: 1561178-17-3

Chemical Structure| 1561178-17-3

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SGC0946 is a selective inhibitor of DOT1L methyltransferase with IC50 of 0.3 nM and can kill mixed lineage leukaemia cells.

4.5 *For Research Use Only !

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Product Citations

Product Citations

Zhou, Jujun ; Deng, Youchao ; Iyamu, Iredia D. ; Horton, John R. ; Yu, Dan ; Hajian, Taraneh , et al.

Abstract: S-Adenosyl-L-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-Et moiety at the sulfur atom off the ribose ring. Compound 11a (IC50 = 0.15 μM) is 10x and 5x more potent against CamA than 6e and 7, resp. The structure of the CamA-DNA-inhibitor complex revealed that 11a adopts a U-shaped conformation, with the two branches folded toward each other, and the aliphatic and aromatic rings at the two ends interacting with one another. 11a occupies the entire hydrophobic surface (apparently unique to CamA) next to the adenosine binding site. Our work presents a hybrid knowledge-based and fragment-based approach to generating CamA inhibitors that would be chem. agents to examine the mechanism(s) of action and therapeutic potentials of CamA in C. difficile infection.

Alternative Products

Product Details of SGC0946

CAS No. :1561178-17-3
Formula : C28H40BrN7O4
M.W : 618.57
SMILES Code : NC1=NC=NC2=C1C(Br)=CN2[C@H]3[C@H](O)[C@H](O)[C@@H](CN(CCCNC(NC4=CC=C(C(C)(C)C)C=C4)=O)C(C)C)O3
MDL No. :MFCD26523136
InChI Key :IQCKJUKAQJINMK-HUBRGWSESA-N
Pubchem ID :56962337

Safety of SGC0946

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301
Precautionary Statements:P301+P310
Class:6.1
UN#:2811
Packing Group:

Related Pathways of SGC0946

epigenetics

Isoform Comparison

Biological Activity

Description
SGC0946 is a selective DOT1LH3K79 methyltransferase) inhibitor, with an IC50 of 0.3 nM. SGC0946 results in G1 arrest, inhibit potential of cell self-renewal and metastatic, and also induces cell differentiation. SGC0946 can be used in studies of leukemia and solid tumors and also serve as a probe to further investigate the cellular mechanism of DOT1L in both normal and diseased cells[1].[2].[3].
Target
  • Histone Methyltransferase

    DOT1L, IC50:0.3 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
A549 cells 5 μM 48 hours SGC0946 in combination with TGF-β1 did not reverse TGF-β1-induced gene expression but reduced PD-L1 protein levels in H358 cells. PMC5549304
H358 cells 5 μM 48 hours SGC0946 in combination with TGF-β1 did not reverse TGF-β1-induced gene expression but reduced PD-L1 protein levels in H358 cells. PMC5549304
786-O cells 0 µM, 1 µM, 2 µM, 5 µM, 10 µM 48 hours SGC0946 drastically reduced the survival of renal cancer cells and increased the apoptosis rate. PMC9906067
A498 cells 0 µM, 1 µM, 2 µM, 5 µM, 10 µM 48 hours SGC0946 drastically reduced the survival of renal cancer cells and increased the apoptosis rate. PMC9906067

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Ornithodoros moubata Larvae Immersion 0.1 μM, 1 μM, 10 μM Single dose, 15 minutes To evaluate the effect of SGC0946 on larval molting, results showed that high concentrations of SGC0946 significantly increased larval molting mortality. PMC7349889
Mice CDX model intraperitoneal administration 20 mg/kg five times per week To evaluate the antitumor effect of SGC0946 in the CDX model. The results showed that SGC0946 had a weaker inhibitory effect on tumors expressing the R231Q mutation. PMC10413674

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.62mL

0.32mL

0.16mL

8.08mL

1.62mL

0.81mL

16.17mL

3.23mL

1.62mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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