TNKS1/PARP5A Inhibitor

Olaparib (AZD2281; KU0059436) is a potent and orally active PARP inhibitor with IC₅₀s of 5 and 1 nM for PARP1 and PARP2, respectively. Olaparib is an autophagy and mitophagy activator. Olaparib cannot cross the intact blood-brain barrier (BBB).

XAV-939 is a Tankyrase inhibitor. XAV-939 has inhibitory activity for TNKS1 and TNKS2 with IC₅₀ values of 5 nM and 2 nM, respectively. XAV-939 also is an enhancer of osteoblastic differentiation of hMSCs. XAV-939 can be used for the research of conditions associated with activated Wnt signaling, such as cancer, fibrotic diseases and conditions associated with low bone formation.

Niraparib (MK-4827) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with IC₅₀s of 3.8 and 2.1 nM, respectively. Niraparib leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity.

Niraparib hydrochloride (MK-4827 hydrochloride) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with IC₅₀s of 3.8 and 2.1 nM, respectively. Niraparib hydrochloride leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity.

G007-LK is a potent and selective inhibitor of TNKS1 and TNKS2, with IC₅₀s of 46 nM and 25 nM, respectively.

Nesuparib (JPI-547) hydrochloride is the orally active inhibitor for PARP 1/2 and Tankyrase 1/2 that inhibits tankyrases 1, tankyrases 2, and PARP 1 with IC₅₀s of 5, 1 and 2 nM, respectively. Nesuparib hydrochloride exhibits antitumor activity and can be used in research of advanced solid tumor.

TNKS-IN-1 is a selective and potent tankyrase (TNKS1/TNKS2) inhibitor with IC₅₀ values of 7.9 nM and 8.7 nM. TNKS-IN-1 induces axin2 accumulation with an EC₅₀ of 1500 nM. TNKS-IN-1 can antagonize the Wnt signal transduction pathway by stabilizing axin proteins and promoting β-catenin degradation. TNKS-IN-1 can be used for the research of colorectal cancer.

PP-048 is a selective dual inhibitor of Polθ/PARP1, with IC₅₀ values of 4.9 nM and 6.8 nM for the Polθ helicase/ATPase domain and PARP1, respectively. PP-048 impairs the compensatory DNA repair capacity of homologous recombination-deficient cells by simultaneously inhibiting the DNA repair functions associated with Polθ and PARP1, thereby exacerbating DNA double-strand damage and inducing apoptosis. PP-048 exhibits more potent selective antiproliferative activity against HR-deficient cancer cells. PP-048 can be used in studies related to Polθ/PARP1 dual-target inhibition, synthetic lethality, DNA damage repair, and HR-deficient triple-negative breast cancer.

Niraparib tosylate (MK-4827 tosylate) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with an IC₅₀ of 3.8 and 2.1 nM, respectively. Niraparib tosylate leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity.

Stenoparib (E7449) is a potent PARP1 and PARP2 inhibitor and also inhibits TNKS1 and TNKS2, with IC₅₀s of 2.0, 1.0, ～50 and ～50 nM for PARP1, PARP2, TNKS1 and TNKS2, respectively, using ³²P-NAD⁺ as substrate.

OUL232 is a potent inhibitor of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15. OUL232 is the most potent PARP10 inhibitor described to date (IC₅₀=7.8 nM), as well as the first PARP12 inhibitor ever reported.

JW 55 is a potent and selective β-catenin signaling pathway inhibitor, which functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2). JW 55 decreases auto-PARsylation of TNKS1/2 in vitro with IC₅₀s of 1.9 μM and 830 nM respectively.

OM-153 is a potent and orally active tankyrase inhibitor with IC₅₀s of 13 nM and 2 nM for tankyrase 1 and tankyrase 2 (TNKS1/2), respectively. OM-153 inhibits luciferase-based Wnt/β-catenin signaling reporter activity with an IC₅₀ value of 0.63 nM. OM-153 shows inhibition of Wnt/β-catenin signaling and proliferation in COLO 320DM.

RK-287107 is a potent and specific tankyrase inhibitor with IC₅₀s of 14.3 and 10.6 nM for tankyrase-1 and tankyrase-2, respectively. RK-287107 blocks colorectal cancer cell growth.

ME0328 is a potent and selective ARTD3/PARP3 inhibitor with an IC₅₀ of 0.89±0.28 μM.

AZ6102 is a potent dual TNKS1 and TNKS2 inhibitor, with IC₅₀s of 3 nM and 1 nM, respectively, and alao has 100-fold selectivity against other PARP family enzymes, with IC₅₀s of 2.0 μM, 0.5 μM, and >3 μM, for PARP1, PARP2, and PARP6, respectively.

Niraparib (MK-4827) tosylate hydrate is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with IC₅₀s of 3.8 and 2.1 nM, respectively. Niraparib tosylate hydrate leads to inhibition of repair of DNA damage, activates apoptosis and shows anti-tumor activity.

Nesuparib (JPI-547) is the orally active inhibitor for PARP 1/2 and Tankyrase 1/2 that inhibits tankyrases 1, tankyrases 2, and PARP 1 with IC₅₀s of 5, 1 and 2 nM, respectively. Nesuparib exhibits antitumor activity and can be used in research of advanced solid tumor.

MN-64 is a potent tankyrase 1 inhibitor, with IC₅₀s of 6 nM, 72 nM, 19.1 μM, and 39.4 μM for TNKS1, TNKS2, ARTD1 and ARTD2, respectively.

K-756 is a direct and selective tankyrase (TNKS) inhibitor, which inhibits the ADP-ribosylation activity of TNKS1 and TNKS2 with IC₅₀s of 31 and 36 nM, respectively.