1. Cell Cycle/DNA Damage Epigenetics Autophagy
  2. Sirtuin Autophagy
  3. SKLB-11A

SKLB-11A is a selective, orally active and allosteric SIRT3 (sirtuin 3) agonist with a Kd value of 4.7 μM. SKLB-11A is highly selective for other members of the SIRT family. SKLB-11A activates autophagy-related signaling pathways, prevents mitochondrial dysfunction, improves cardiac function in Doxorubicin (HY-15142A)-induced cardiotoxicity and myocardial ischemia/reperfusion models.

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SKLB-11A

SKLB-11A Chemical Structure

CAS No. : 433953-86-7

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10 mM * 1 mL in DMSO
ready for reconstitution
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Description

SKLB-11A is a selective, orally active and allosteric SIRT3 (sirtuin 3) agonist with a Kd value of 4.7 μM. SKLB-11A is highly selective for other members of the SIRT family. SKLB-11A activates autophagy-related signaling pathways, prevents mitochondrial dysfunction, improves cardiac function in Doxorubicin (HY-15142A)-induced cardiotoxicity and myocardial ischemia/reperfusion models[1].

IC50 & Target

SIRT3

4.7 μM (Kd)

In Vitro

SKLB-11A enhances SIRT3 deacetylation activity with an EC50 of 21.95 μM[1].
SKLB-11A (0.625-5 μM; 24 h) does not alter SIRT3 protein levels but significantly enhances SIRT3 activity in H9c2 cells[1].
SKLB-11A binds to SIRT3 with high affinity and enhances its interaction with the p53-Ac substrate[1].
SKLB-11A (5-20 μM; 24 h) ameliorates Doxorubicin-induced mitochondrial damage and promotes SIRT3-mediated autophagy in H9c2 cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: H9c2 cells
Concentration: 0.625 μM, 1.25 μM, 2.5 μM, 5 μM
Incubation Time: 24 h
Result: Induced deacetylation at K122 and K68, resulting in enhanced MnSOD enzymatic activity.
Activated endogenous SIRT3 deacetylation in H9c2 cells.

Western Blot Analysis[1]

Cell Line: H9c2 cells
Concentration: 5 μM, 10 μM, 20 μM
Incubation Time: 24 h
Result: Increased LC3-II expression and reduced p62 levels, indicating enhanced autophagic flux.
Increased the expression of PINK1 and Parkin, and promoted colocalization of mitochondria with Parkin and LC3-II.
In Vivo

SKLB-11A (10-20 mg/kg; oral gavage; daily; for 7 days) pretreatment can repress Doxorubicin-induced cardiac dysfunction in mice[1].
SKLB-11A (20 mg/kg; oral gavage; daily; for 7 days) treatment alleviated ischemia/reperfusion (I/R)-induced myocardial injury in mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male C57BL/6J mice (8 weeks, ~23 g)[1]
Dosage: 10 and 20 mg/kg/day
Administration: Oral gavage; daily; for 7 days; then injected Doxorubicin intraperitoneally for 2 weeks
Result: Significantly restored left ventricular ejection fraction (EF) and fractional shortening (FS) in a dose-dependent manner.
Partially reversed Doxorubicin-induced weight loss and reduced serum markers of myocardial injury, including LDH, CK-MB, and BNP.
Preserved myocardial structure and alleviated pathological damage.
Demonstrated no apparent toxicity at effective doses, as evidenced by preserved organ histology in the heart, liver, spleen, lungs, and kidneys.
Animal Model: Male C57BL/6J mice (8-12 weeks old) was induced myocardial ischemia-reperfusion (I/R) injury[1].
Dosage: 20 mg/kg
Administration: Oral gavage; daily; for 7 days
Result: Restored cardiac function impaired by I/R injury.
Partially reversed I/R-induced elevations in serum myocardial injury markers, including LDH, CK-MB, and BNP.
Markedly reduced I/R-induced cardiac fibrosis.
Molecular Weight

350.35

Formula

C19H15FN4O2

CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

COC(C1=C(N)N(CC2=CC=C(F)C=C2)C3=NC4=CC=CC=C4N=C31)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 7.78 mg/mL (22.21 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.8543 mL 14.2714 mL 28.5429 mL
5 mM 0.5709 mL 2.8543 mL 5.7086 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.8543 mL 14.2714 mL 28.5429 mL 71.3572 mL
5 mM 0.5709 mL 2.8543 mL 5.7086 mL 14.2714 mL
10 mM 0.2854 mL 1.4271 mL 2.8543 mL 7.1357 mL
15 mM 0.1903 mL 0.9514 mL 1.9029 mL 4.7571 mL
20 mM 0.1427 mL 0.7136 mL 1.4271 mL 3.5679 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
SKLB-11A
Cat. No.:
HY-173572
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