SIRT1 Inhibitor

SIRT1-IN-4 (Compound 8c) is a SIRT1 inhibitor, with an IC₅₀ of 10.04 μM. SIRT1-IN-4 can be used for the research of cancer.

(S)-Selisistat ((S)-EX-527) is a potent and selective SIRT1 inhibitor, with an IC₅₀ of 98 nM.

4'-Bromo-resveratrol (4′‐BR) is a dual SIRT1/SIRT3 inhibitor with an IC₅₀ of 0.2 mM for both targets. 4'-Bromo-resveratrol induces caspase-dependent apoptosis, induces G0/G1 cell cycle arrest, and inhiibits proliferation. 4'-Bromo-resveratrol reduces lactate production, glucose uptake, and NAD⁺/NADH ratio, and downregulates lactate dehydrogenase A and glucose transporter 1 (GLUT1). 4'-Bromo-resveratrol can be used for the research of melanoma.

SIRT-IN-1 is a potent inhibitor of SIRT1/2/3, with IC₅₀s of 15, 10, 33 nM, respectively.

SIRT6-IN-3 (compound 8a) is a selective inhibitor of SIRT6 (IC₅₀=7.49 μM). SIRT6-IN-3 inhibits pancreatic ductal adenocarcinoma (PDAC) cells proliferation and induces apoptosis. SIRT6-IN-3 increases the sensitivity of cancer cells to gemcitabine (HY-17026) via blocking the DNA damage repair pathway. SIRT6-IN-3 is used in pancreatic cancer research.

SIRT1-IN-2 (compound 3h) is a potent and selective SIRT1 (silent information regulator 1) inhibitor, with an IC₅₀ of 1.6 μM.

SIRT1-IN-3 (compound 3j) is a potent and selective SIRT1 inhibitor, with an IC₅₀ of 4.2 μM.

JGB1741 (ILS-JGB-1741) is a potent and specific SIRT1 activity inhibitor with an IC₅₀ of ∼15 μM. JGB1741 is a weak SIRT2 and SIRT3 inhibitor with an all IC₅₀>100 μM. JGB1741 increases the acetylated p53 levels leading to p53-mediated apoptosis with modulation of Bax/Bcl2 ratio, cytochrome c release and PARP cleavage. JGB1741 has the potential for breast cancer research.

Suramin is a reversible and competitive protein-tyrosine phosphatases (PTPases) inhibitor. Suramin is a potent inhibitor of sirtuins: SirT1 (IC₅₀=297 nM), SirT2 (IC₅₀=1.15 μM), and SirT5 (IC₅₀=22 μM). Suramin is a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC₅₀=5 μM). Suramin is a potent SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitor.Suramin efficiently inhibits IP5K and is an antiparasitic, anti-neoplastic and anti-angiogenic agent.

SIRT5 inhibitor 4 (compound 11) is a potent, selective SIRT5 inhibitor with IC₅₀ values of 26.4 and >400μM for SIRT5 and other SIRT subtype, respectively.

Sirtuin-1 inhibitor 1 (Compound 8) is an inhibitor of Sirtuin-1 that plays important roles in obesity-induced diabetes and aging-related diseases.

SIRT2-IN-11 (AEM1) is a selective SIRT2 inhibitor with an IC₅₀ value of 18.5 μM. SIRT2-IN-11 p53-dependently induces apoptosis, activates expression of CDKN1A, PUMA and NOXA, and increases acetylation of p53. SIRT2-IN-11 can be used for the research of p53-related cancers.

AC-93253 is a selective, potent SIRT2 inhibitor. AC93253 can inhibit SIRT2 with an IC₅₀ value of 6 μM. AC93253 can be used for the research of tumors.

SIRT2-IN-9 (compound 12) is a selective inhibitor of SRIT2 with an IC₅₀ value of 1.3 μM. SIRT2-IN-9 inhibits proliferative activity of MCF-7 breast cancer cells. SIRT2-IN-9 can be used for the research of cancer.

CHIC35, an analog of EX-527, is a potent and selective inhibitor of SIRT1 (IC₅₀=0.124 μM). CHIC35 shows potential selective inhibition against SIRT1 over SIRT2 (IC₅₀=2.8 μM) or SIRT3 (IC₅₀>100 μM). CHIC35 has anti-inflammatory effects and can be used for CHARGE syndrome research.

SIRT1/2/3-IN-2 (compound 9) is a potent SIRT inhibitor, with inhibition rates of 27%, 72%, and 71% targeting SIRT1, SIRT2, and SIRT3, respectively, at 200 μM. SIRT3 is a potential tumor suppressor or promoter, and its increased transcription may be associated with lymph node-positive breast cancer and oral squamous cell carcinoma.

SPC-180002 is a SIRT1/3 dual inhibitor, with IC₅₀ values of 1.13 and 5.41 μM, respectively. SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. SPC-180002 strongly inhibits cell cycle progression and cancer cell growth. SPC-180002 activates the Nrf2 signaling pathway.

NH4-6 is a SIRT2 inhibitor with an IC₅₀ of 0.032 μM against SIRT2 and an IC₅₀ of 3 μM against SIRT1. NH4-6 inhibits the deacetylase activity of SIRT1. As a cytotoxic agent, NH4-6 reduces cancer cell viability, suppresses anchorage-independent growth of cancer cells, induces acetylation of α-tubulin, and promotes acetylation of p53. NH4-6 can be used in the research of breast cancer.

Sirt1/2-IN-5 is a SIRT1/SIRT2 inhibitor with human SIRT1 IC₅₀ 0.3 μM and human SIRT2 IC₅₀ values 1.2 μM and pIC₅₀ 5.82. Sirt1/2-IN-5 inhibits NAD⁺-dependent deacetylase activity of SIRT1 and SIRT2. Sirt1/2-IN-5 can be used for the research of cancer, neurodegenerative disease.

Nicotinamide hydrochloride is a form of vitamin B3 or niacin. Nicotinamide hydrochloride inhibits SIRT2 activity (IC₅₀: 2 μM). Nicotinamide hydrochloride also inhibits SIRT1. Nicotinamide hydrochloride increases cellular NAD₊, ATP, ROS levels. Nicotinamide hydrochloride inhibits tumor growth and improves survival. Nicotinamide hydrochloride also has anti-HBV activity.