SIRT6 activator 12q

• CAT Number: I041984
• CAS Number: 2601734-99-8
• Molecular Formula: C31H22N2O2
• Molecular Weight: 454.52
• Purity: ≥95%
• Synonyms: N-benzhydryl-2-(1-benzofuran-2-yl)quinoline-4-carboxamide
• InChI: InChI=1S/C31H22N2O2/c34-31(33-30(21-11-3-1-4-12-21)22-13-5-2-6-14-22)25-20-27(32-26-17-9-8-16-24(25)26)29-19-23-15-7-10-18-28(23)35-29/h1-20,30H,(H,33,34)
• InChIKey: JNULQPRWYHVXHT-UHFFFAOYSA-N
• SMILES: C1=CC=C(C=C1)C(C2=CC=CC=C2)NC(=O)C3=CC(=NC4=CC=CC=C43)C5=CC6=CC=CC=C6O5

SIRT6 activator 12q is potent, selective and orally active SIRT6 activator with IC50 values of 171.20, >200, >200, >200, 0.58 μM for SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, respectively. SIRT6 activator 12q inhibits cell growth and migration. SIRT6 activator 12q induces Apoptosis and cell cycle arrest at G2 phase. SIRT6 activator 12q shows anticancer activity[1].
SIRT6 activator 12q (compound12q) (2.5, 5, 10 µM; 14, 18 days) inhibits the colony formation of PANC-1, BXPC-3, MIAPaCa-2, and AsPC-1 cells in a dose-dependent manner[1].
SIRT6 activator 12q (10, 25, 50 µM; 48 h) induces apoptosis and cell cycle arrest at G2 phase in a dose-dependent manner[1].
SIRT6 activator 12q (12.5, 25, 50 µM; 48 h) decreases the protein expression of H3K9ac, H3K18ac, and H3K56ac in PANC-1 and BXPC-3 cells in a dose-dependent manner[1].
SIRT6 activator 12q (100, 150 mg/kg; p.o.; daily for 30 days) inhibites the tumer growth in a dose-dependent manner in mouse[1].
Pharmacokinetic Parameters of SIRT6 activator 12q in Male Sprague-Dawley rats[1].

PK parameter
10 mg/kg p.o.
2 mg/kg i.v.

CL (L/h/kg)

0.6 ± 0.08

Vss (L/kg)

1112.8 ± 322.84

T1/2 (h)
7.52 ± 1.44
9.06 ± 0.21

Tmax (h)
2.00 ± 0.00
0.08 ± 0.00

Cmax (ng/mL)
98.45 ± 3.62
5123.70 ± 905.5

AUC(0-t)(h·ng/mL)
704.67 ± 80.47
3326.13 ± 476.4

AUC(0-∞)(h·ng/mL)
755.57 ± 80.74
3381.49 ± 468.48

F (%)
4.24 ± 0.48

Male Sprague-Dawley rats, 2 mg/kg iv; 10 mg/kg po[1]

Reference

[1]. Chen X, et al. Discovery of Potent Small-Molecule SIRT6 Activators: Structure-Activity Relationship and Anti-Pancreatic Ductal Adenocarcinoma Activity. J Med Chem. 2020 Sep 24;63(18):10474-10495.
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