parp-1-in-1

PARP-1-IN-1 is a highly selective and orally active inhibitor of the enzyme PARP-1 with an IC50 of 0.96 nM, exhibiting excellent tolerance and significant activity in a single dose in the MDA-MB-436 xenotransplantation model [1].

Compound B6, also known as TOPOI/PARP-1-IN-1, is a dual inhibitor targeting TOPOI and PARP, exhibiting low cytotoxicity and oral activity with a PARP1 IC 50 of 0.09 μM. This compound effectively inhibits cancer cell proliferation and migration, induces cell cycle arrest at the G0/G1 phase, and triggers apoptosis. In murine models, TOPOI/PARP-1-IN-1 demonstrated a tumor growth inhibition rate (TGI) of 75.4% [1].

PARP-1-IN-13 (Compound 19c) is a potent PARP-1 inhibitor with an IC50 of 26 nM, hindering DNA single-strand break repair and exacerbating double-strand breaks, leading to apoptosis in cancer cells via the mitochondrial pathway [1].

PARP1-IN-17 is an inhibitor that targets PARP-1 (IC50=19.24 nM ) with a slightly reduced affinity for PARP-2 (IC50=32.58 nM ) and induces apoptosis. It exhibits robust anti-proliferative activity [1].

ATR/PARP1-IN-1 is a dual inhibitor of ATR/PARP1, exhibiting an IC50 of 17.3 nM for ATR and 0.38 nM for PARP1. It effectively reduces cell viability, induces apoptosis, and causes DNA damage. In triple-negative breast cancer (TNBC) models, ATR/PARP1-IN-1 significantly inhibits colony formation, migration, and invasion. Additionally, in MDA-MB-468 xenograft mouse models, it suppresses tumor growth without significant changes in body weight.

PARP1-IN-11 (compound 49) is a potent PARP1 inhibitor with an IC50 value of 0.082 μM, demonstrating complete inhibition of PARP1 and substantial inhibition of PARP3, TNKS1, and TNKS2 [1].

PARP1-IN-10 (compound 12c) is a highly potent and non-cytotoxic PARP1 inhibitor with an in vitro IC50 value of 50.62 nM, effectively inducing cell cycle arrest at the G2/M phase and apoptosis, while significantly augmenting the cytotoxic effects of temozolomide (TMZ) [1].

PARP1-IN-12, a potent inhibitor of PARP1, demonstrates an IC50 value of 2.99 nM. It exhibits antiproliferative effects, induces apoptosis, and causes cell cycle arrest in the G2/M phase. Additionally, PARP1-IN-12 induces DNA double-strand breaks (DSBs) in BRCA-deficient cells.

PARP1-IN-15 (Compound 6) is a PARP1 inhibitor that also inhibits tankyrase (TNKS) and promotes DNA double-strand breaks, leading to tumor cell apoptosis. It exhibits anti-cancer activity in triple-negative breast cancer (TNBC) cells and patient-derived organoids, making it useful for TNBC research, including cases with or without BRCA1 mutations [1].

PARP1-IN-14 (compound 19k) is a potent PARP1 inhibitor with an IC50 of 0.6 ± 0.1 nM, displaying antiproliferative effects on MDA-MB-436 (BRCA1 −/−) and Capan-1 (BRCA2 −/−) cells, with IC50 values below 0.3 nM [1].

PARP1-IN-16 (compound 12a) is a potent PARP1 inhibitor with an IC50 value of 1.89 nM, capable of halting the cell cycle at the S phase and inducing apoptosis in HCT-116 cells [1].

PARP1-IN-18 (compound 25), a potent PARP1 inhibitor, exhibits an IC 50 of 2.7 nM and has demonstrated anticancer effects [1].

PARP1-IN-19, a PARP1 inhibitor, exhibits antitumor effects (CN107955001A; Embodiment 3) [1].

1. Dehydrocorydaline (13-Methylpalmatine) exerts anti-metastatic potential via suppression of MMPs and Bcl-2 signaling in NSC-LC cells. 2. Dehydrocorydaline stimulates p38 MAPK activation, which can enhance heterodimerization of MyoD and E proteins, thus resulting in MyoD activation and myoblast differentiation. 3. Dehydrocorydaline shows antiplatelet effects, it inhibits thrombin-induced platelet aggregation in a low dose ( IC50= 34.914 ug/mL). 4. Dehydrocorydaline has anti-inflammatory and antinociceptive effects. 5. Dehydrocorydaline inhibits MCF-7 cell proliferation by inducing apoptosis mediated by regulating Bax/Bcl-2, activating caspases as well as cleaving PARP.

CSRM617 hydrochloride is a selective small-molecule inhibitor of the transcription factor ONECUT2 (OC2, a master regulator of androgen receptor), with a Kd of 7.43 µM in SPR assays, directly binding to the OC2-HOX domain. CSRM617 hydrochloride induces apoptosis through the appearance of cleaved Caspase-3 and PARP and is well tolerated in the mouse model of prostate cancer [1].

PARP1/2/TNKS1/2-IN-1 is a multi-target inhibitor of PARP-1, PARP-2, TNKS1, and TNKS2, with potential anti-tumor activity that induces apoptosis.

3-Aminobenzamide (PARP-IN-1) is a potent PARP inhibitor (IC50 < 50 nM in CHO cells) and mediates oxidant-induced myocyte dysfunction during reperfusion.

PARP-1-IN-2 is a potent PARP1 inhibitor that crosses the blood-brain barrier (IC50: 149 nM).PARP-1-IN-2 showed significant antiproliferative activity against the human lung adenocarcinoma epithelial cell line A549 in cellular assays.PARP-1-IN-2 induced apoptosis in A549 cells.

TNKS-2-IN-1 is a TNKS-2 inhibitor.TNKS-2-IN-1 inhibits TNKS-1 and TNKS-2 with IC50s of 259 nM and 1100 nM, respectively.TNKS-2-IN-1 has antimicrobial activity against E. coli and S. aureus.TNKS-2-IN-1 inhibits the release of IL-1β from the NLRP3 inflammasome (IC50: 5 μM) by inhibiting IL-1β release from ATP-stimulated J1A.774 cells.

PARP1-IN-8 (N-(3-chlorophenyl)-3-(1-oxo-4-phenylphthalazin-2(1H)-yl)propanamide) is an effective inhibito of PARP1 (IC50 = 97 nM).

PARP-2-IN-1 is a potent and selective inhibitor of PARP-2 (IC50 of 11.5 nM).

PARP/PI3K-IN-1 is a novel dual poly (ADP-ribose) polymerase (PARP) and phosphatidylinositol 3-kinase (PI3K) dual inhibitor with anticancer, antitumour and antiproliferative activities for the study of breast, pancreatic and lung cancers.

NMS-P515 is an effective, orally active, and stereospecific PARP-1 inhibitor (Kd: 16 nM and an IC50: 27 nM (in Hela cells)). It has anti-tumor activity.

Tubulin polymerization-IN-68 (compound 32) serves as a tubulin inhibitor, disrupting cellular microtubule networks by hindering tubulin polymerization. It also upregulates PARP-1 and caspase-3 expression, thereby inducing apoptosis and exhibiting anticancer properties. Notably, Tubulin polymerization-IN-68 effectively suppresses HepG2 cells with an IC50 of 93 nM and markedly reduces the growth of HepG2 xenograft tumors in nude mice through oral administration.