SIRT3 Inhibitor

3-TYP is an inhibitor of SIRT3 (IC₅₀of 38 μM) and an inhibitor of Methionine Adenosyltransferase (MAT) 2 and Indoleamine 2,3-Dioxygenase (IDO). There may be many off-target sites for 3-TYP that need to be examined, such as NAD-dependent enzymes, including dehydrogenases.

AGK2 is a selective SIRT2 inhibitor with an IC₅₀ of 3.5 μM. AGK2 inhibits SIRT1 and SIRT3 with IC₅₀s of 30 and 91 μM, respectively.

OXPHOS-IN-3 is a mitochondria-targeted dual OXPHOS/glycolysis inhibitor. OXPHOS-IN-3 exhibits potent antiproliferative activity against pancreatic cancer cells. OXPHOS-IN-3 induces mitochondrial dysfunction, ferroptosis, and immunogenic cell death (ICD). OXPHOS-IN-3 shows potent antitumor activity in pancreatic ductal adenocarcinoma (PDAC) models.

Tenovin-6, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC₅₀s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH).

SIRT-IN-2 is a potent inhibitor of SIRT1/2/3, with IC₅₀s of 4, 4, 7 nM, respectively.

SIRT1-IN-1 is a selective SIRT1 inhibitor with an IC₅₀ of 0.205 μM. SIRT1-IN-1 inhibits SIRT2 with an IC₅₀ of 11.5 μM. SIRT1-IN-1, a indole, is a cytomegalovirus (CMV) inhibitors and has antiviral activity.

SIRT6-IN-6 (compound 6d) is a potent and selective SIRT6 inhibitor with an IC₅₀ of 4.93 μM and a K_i of ~10 μM. SIRT6-IN-6 shows selectivity against other members of the HDAC family (SIRT1-3 and HDAC1-11). SIRT6-IN-6 significantly increases the level of glucose transporter GLUT-1, thereby reducing blood glucose in a mouse model of type 2 diabetes. SIRT6-IN-6 can be used for type 2 diabetes research.

Tenovin-6 Hydrochloride, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 Hydrochloride inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC₅₀s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 Hydrochloride also inhibits dihydroorotate dehydrogenase (DHODH).

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.

SIRT3-IN-1 (compound 17f) is a SIRT3 inhibitor, with IC₅₀ of 0.043 μM. SIRT3-IN-1 can be used in the research of acute leukemia (AML).

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

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.

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.

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.

hsa62 is a dual inhibitor for SIRT1 and SIRT2, with IC₅₀ of 1.3 and 5.5 μM, respectively.

C1A is a class I/II HDACs and sirtuin inhibitor with an IC₅₀ of 479 nM for HDAC6. C1A induces sustained acetylation of HDAC6 substrates, α-tubulin and HSP90. C1A shows srtong anticancer effcts, and induces apoptosis in cancer cells.