DNA-PK-IN-3 is a highly potent inhibitor of DNA-PK. This compound exerts a synergistic effect when combined with radiotherapy and chemotherapy, resulting in enhanced therapeutic outcomes and significant inhibition of tumor growth. Furthermore, DNA-PK-IN-3 demonstrates remarkable efficacy in reducing damage to normal cells, effectively minimizing adverse side effects. Due to these compelling properties, DNA-PK-IN-3 holds great potential for cancer research applications[1].

DNA-PK-IN-1 is a potent inhibitor of DNA-PK. DNA-PK-IN-1 has potential for cancer disease research.

DNA-PK-IN-2 is a highly effective inhibitor of DNA-dependent protein kinase (DNA-PK), which is a complex enzyme composed of Ku70/Ku80 heterodimer and DNA-PK catalytic subunit (DNA-PKcs). With its potential applications in cancer research, DNA-PK-IN-2 demonstrates promise as a valuable tool for studying cancer diseases [1].

DNA-PK-IN-8 is a potent, selective, and orally active inhibitor of DNA-dependent protein kinase (DNA-PK), demonstrating an IC50 value of 0.8 nM. It displays synergistic antiproliferative effects across various cancer cell lines and notably reduces HL-60 tumor growth when combined with Doxorubicin [1].

DNA-PK-IN-10 is a DNA-PK inhibitor utilized in the research of breast cancer and non-small cell lung cancer [1].

DNA-PK-IN-9 (also known as compound YK6) is a highly potent inhibitor of DNA-dependent protein kinase (DNA-PK), displaying an IC50 value of 10.47 nM. DNA-PK-IN-9 holds significant potential in anticancer research [1].

DNA-PK-IN-6, a robust DNA-PK inhibitor, effectively hampers the activity of DNA-PKcs, thereby significantly impairing the DNA repair mechanism in tumors and instigating apoptosis in cells. Additionally, DNA-PK-IN-6 amplifies the responsiveness of tumor tissues to radiotherapy, overcomes the challenge of drug resistance, and augments its inhibitory impact on a diverse range of solid and hematological tumors[1].

DNA-PK-IN-4 (WO2021209055A1, compound 27), an imidazolinone derivative compound, is a highly effective inhibitor of DNA-PK, specifically targeting DNA-PKcs activity. By inhibiting DNA-PKcs, the compound significantly impairs tumor DNA repair mechanisms and triggers apoptosis in cells. With its potential application in cancer research, DNA-PK-IN-4 holds promise for further investigation [1].

AMA-37 is a selective, reversible, and ATP-competitive DNA-PK inhibitor.

NU 7026 (DNA-PK Inhibitor II) is an effective DNA-PK inhibitor (IC50: 0.23 μM, in cell-free assays), 60-fold selective for DNA-PK than PI3K and no inhibition against both ATM and ATR.

DNA-PK-IN-5 is a potent inhibitor of DNA-PK. DNA-PK-IN-5 inhibits the activity of DNA-PKcs, significantly reduces tumour DNA repair and induces apoptosis. DNA-PK-IN-5 improves the sensitivity of tumour tissue to radiotherapy, overcomes drug resistance problems and improves the inhibition of many solid and haematological tumours.

DNA-PK-IN-7 is a potent DNA-PK inhibitor (IC50= 1 nM) (WO2021104277A1, compound 5).

Camonsertib (RP-3500) is a selective, orally active ATR kinase inhibitor (ATRi) with an IC50: 1.00 nM in biochemical assays and exhibits potent antitumour effects. Camonsertib is 30 times more selective for ATR than mTOR (IC50: 120 nM) and is a more active inhibitor of ATM, DNA-PK and PI3Kα kinases. PK and PI3Kα kinases.

Nedisertib (M3814) (M3814) is a specific inhibitor of DNA-dependent Protein Kinase (DNA-PK, IC50: <3 nM).

LY294002 (SF 1101) is a broad-spectrum inhibitor of PI3K, inhibiting PI3Kα, PI3Kδ, and PI3Kβ (IC50=0.5/0.57/0.97 μM). LY294002 is also an inhibitor of DNA-PK (IC50=1.4 μM) and an inhibitor of CK2 (IC50=98 nM). LY294002 activates apoptosis and autophagy.

PIK-75, a DNA-PK and PI3K inhibitor, suppresses DNA-PK(IC50=2 nM), p110α(IC50=5.8 nM) and p110γ(IC50=76 nM).

IC 86621 is a selective and reversible ATP-competitive inhibitor of DNA-PK with an IC50 of 120 nM. IC 86621 increases DNA double-strand break(DSB)-induced antitumor activity with an EC50 of 68 µM for DNA-PK mediated cellular DSB repair.

LY-294002 hydrochloride (NSC 697286) is a synthetic molecule inhibitor of PI3Kα/δ/β (IC50: 0.5/0.57/0.97 μM, in cell-free assays); more stable than Wortmannin in solution, and also is a blocker of autophagosome formation.

SAR-260301 is an orally available and selective inhibitor of PI3Kβ (IC50: 23 nM).

STL127705 (Compound L) is a potent Ku 70/80 heterodimer protein inhibitor and inhibits Ku70/80-DNA interaction with IC50 of 3.5 μM. STL127705 inhibits the activation of Ku-dependent DNA-PKCS kinase with IC50 of 2.5 μM.

Wortmannin (SL-2052) is a PI3K inhibitor (IC50=3 nM) that is covalent and irreversible. Wortmannin is also an inhibitor of PlK1 and PlK3 (IC50=5.8/48 nM) that blocks autophagy.

OSI-027 (ASP4786) is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, and more than 100-fold selectivity observed for mTOR than PI3Kα, PI3Kβ, PI3Kγ or DNA-PK. Phase 1.

KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor.

NU7441 (KU-57788 (NU7441)) is a highly effective and specific DNA-PK inhibitor (IC50: 14 nM).

Torin 2(IC50=0.25 nM), a specific and effective mTOR inhibitor, is the 800-fold greater specific activity for mTOR than PI3K and improves pharmacokinetic properties. The EC50 of Torin 2 for ATM/ATR/DNA-PK inhibition is 28 nM/35 nM/118 nM, respectively.

(R)-Nedisertib is a less active R-enantiomer of Nedisertib(IC50 in the range of 7-30 nM for DNA-PK).

Pictilisib dimethanesulfonate (GDC-0941 2 MeSO3H salt) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).

DMNB (6-Nitroveratraldehyde) is DNA-dependent protein kinase (DNA-PK) inhibitor with IC50 of 15 μM, an enzyme involved in the non-homologous end-joining (NHEJ) pathway of double-stranded DNA break (DSB) repair in human cells.

Compound 401 (2-morpholino-4H-pyrimido[2,1-a]isoquinolin-4-one) is a synthetic DNA-PK inhibitor (IC50 = 0.28 μM) that also targets mTOR but not PI3K.

NU6027 is a potent ATR/CDK inhibitor, inhibits CDK1/2, ATR and DNA-PK with Ki of 2.5 μM/1.3 μM, 0.4 μM and 2.2 μM, enter cells more readily than the 6-aminopurine-based inhibitors.

KU-0058684 is a potent PARP and DNA-PK inhibitors.

ATR-IN-20, a potent ATM/ATR inhibitor, showcases an IC50 value of 3 nM. It also exhibits inhibitory activity against mTOR with an IC50 of 18 nM, while maintaining selectivity over PI3Kα (100 nM), ATM (100 nM), and DNA-PK (662 nM). Additionally, ATR-IN-20 has an excellent pharmacokinetic profile with an oral bioavailability (F) of 30%, and demonstrates anticancer effects.

PK11000 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.

CC-115 is a inhibitor of mTOR/DNA-PK (IC50= 21/ 13 nM).

KU-0060648 is a dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ with IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively, less inhibition of PI3Kγ with IC50 of 0.59 μM.

Voxtalisib (XL765) (SAR245409, XL765) is a dual inhibitor of mTOR/PI3K, mostly for p110γ with IC50 of 9 nM; also inhibits DNA-PK and mTOR. Phase 1/2.

PIK-90, a DNA-PK and PI3K inhibitor, suppresses p110α( IC50=11 nM), p110γ(IC50=18 nM) and DNA-PK(IC50=13 nM) .

PP-121 is a multi-targeted inhibitor of PDGFR (IC50: 2 nM), Hck (IC50: 8 nM), mTOR (IC50: 10 nM), VEGFR2(IC50: 12 nM), Src (IC50: 14 nM) and Abl (IC50: 18 nM) , also inhibits DNA-PK (IC50: 60 nM).

ZL-2201 is a potent inhibitor of DNA-PK, demonstrating an IC50 value of 1 nM.

Yhhu6669 is an anti-HBV agent that suppresses viral DNA and replication by promoting DNA-free capsid assembly, effectively reducing HBV DNA and HBcAg levels in AAV/HBV-infected mice and demonstrating favorable pharmacokinetic (PK) properties [1].

(Rac)-Nedisertib is a racemate of Nedisertib, a potent inhibitor of DNA-PK(IC50 of <3 nM).

Canfosfamide (TLK-286, TER286), a glutathione analogue prodrug, becomes activated by glutathione S-transferase P1-1 to induce apoptosis and inhibit DNA-dependent protein kinase's (DNA-PK) catalytic kinase activity. Upon activation, it generates an anticancer alkylating agent and a glutathione derivative, making it useful in researching malignancies [1] [2] [3].

NU-7031 is a potent DNA-PK inhibitor with potential anticancer activity.

PI-103 is a potent, cell-permeable, ATP-competitive inhibitor of PI3K family members (IC50s: 2/3/3/15/30/23 nM for p110α/β/δ/γ, mTOR, and DNA-PK).

Samotolisib (LY3023414) is an oral ATP competitive inhibitor of the class I PI3K isoforms, DNA-PK, and mTOR. Samotolisib (LY3023414) has been used in trials studying the treatment of Neoplasm, Solid Tumor, COLON CANCER, BREAST CANCER, and Advanced Cancer, among others.

AZD-7648 is an inhibitor of DNA-dependent protein kinase (DNA-PK) with the IC50 of 0.63 nM in an enzyme assay,has anti-tumor activity.

CAL-101 (Idelalisib) is a selective inhibitor of p110δ(IC50 : 2.5 nM; in cell-free assays); shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR.

QLT0267 is an inhibitor targeting integrin-linked kinase (ILK; IC50= 26 nM), showing over 10-fold selectivity against cyclin-dependent kinases 1, 2, and 5 (Cdk1, Cdk2, and Cdk5), and over 1,000-fold selectivity against C-terminal Src kinase (CSK), DNA-PK, Pim-1, Akt, PKC, and casein kinase 2 (CK2) at a concentration of 10 mg/ml. This compound effectively inhibits the proliferation of NPA187 papillary thyroid cancer cells with an IC50 of approximately 3 µM and induces apoptosis in NPA187, DRO, and K4 cancer cell lines. In vivo studies reveal that QLT0267, administered at 100 mg/kg, significantly reduces tumor growth in a DRO mouse xenograft model and diminishes both tumor volume and intratumoral vascularization in a U87MG glioblastoma mouse xenograft model, showcasing its potential for therapeutic applications in cancer treatment.

PI3K-IN-1 (Voxtalisib Analogue) is a dual inhibitor of mTOR/PI3K, mostly for p110γ , also inhibits DNA-PK and mTOR.