DNA-PK-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/DNA-PK.html DNA-PKDNA-dependent protein kinaseDNA-PK (DNA-dependent protein kinase) is a nuclear serine/threonine protein kinase composed of a large catalytic subunit(DNA-PKcs) and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the non

2、homologous end-joining(NHEJ) pathway of DNA double-strand breaks repair. DNA-PK specifically requires association with DNA for its kinase activity, playsimportant roles in the regulation of different DNA transactions, including transcription, replication and DNA repair, as well as in themaintenance

3、of telomeres.The assembly of DNA-PK at DSB ends serves as a platform to recruit Artemis, DNA ligase IV and other NHEJ factors that areinvolved in end-processing and ligation. Within the DNA-PK complex, Ku proteins confer high affinity to DSB ends, and function asearly sensors. The subsequent recruit

4、ment of DNA-PKcs to DSBs via the Ku proteins triggers the activation of DNA-PKcs, a memberof the phosphatidylinositol 3-kinase-related kinase (PIKK) family. Upon activation, DNA-PKcs phosphorylates a number ofsubstrates, including H2AX, XRCC4, Artemis and most importantly, DNA-PKcs itself. Autophosp

5、horylation of DNA-PKcs occurs atnumerous Ser/Thr residues throughout the kinase, and has been shown to mediate NHEJ.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/DNA-PK.html DNA-PK HYPERLINK https:/www.MedChemE/Targets/DNA-PK.html HYPERLINK https:/www.MedChemE/Targets/DNA-PK.html Inhibitors H

6、YPERLINK https:/www.MedChemE/ama-37.html AMA-37 HYPERLINK https:/www.MedChemE/ama-37.html HYPERLINK https:/www.MedChemE/AZD-7648.html AZD-7648Cat. No.: HY-100706 Cat. No.: HY-111783AMA-37, an Arylmorpholine analog, isATP-competitive DNA-PK inhibitor, with IC50values of 0.27 M (DNA-PK), 32 M (p110),

7、3.7 M(p110), and 22 M (p110), respectively.AZD-7648 is a potent and selective DNA-PKinhibitor. Anti-tumor activity.Purity: 99.15%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.89%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg, 250 m

8、g HYPERLINK https:/www.MedChemE/bay-8400.html BAY-8400 HYPERLINK https:/www.MedChemE/bay-8400.html HYPERLINK https:/www.MedChemE/CC-115.html CC-115Cat. No.: HY-132293 Cat. No.: HY-16962BAY-8400 is an orally active, potent and selectiveDNA-dependent protein kinase (DNA-PK) inhibitor(IC =81 nM). BAY-8

9、400 can be used for the50research of cancer.CC-115 is a potent and dual DNA-PK and mTORkinase inhibitor with IC s of 13 nM and 21 nM,50respectively. CC-115 blocks both mTORC1 andmTORC2 signaling.Purity: 99.50%Clinical Data: No Development ReportedSize: 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity:

10、98.04%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg HYPERLINK https:/www.MedChemE/CC-115-hydrochloride.html CC-115 HYPERLINK https:/www.MedChemE/CC-115-hydrochloride.html HYPERLINK https:/www.MedChemE/CC-115-hydrochloride.html hydrochloride HYPERLINK https:/www.MedChemE/CC-115-hydrochlo

11、ride.html HYPERLINK https:/www.MedChemE/Compound-401.html Compound HYPERLINK https:/www.MedChemE/Compound-401.html HYPERLINK https:/www.MedChemE/Compound-401.html 401Cat. No.: HY-16962A Cat. No.: HY-19341CC-115 hydrochloride is a potent and dual DNA-PKand mTOR kinase inhibitor with IC s of 13 nM50an

12、d 21 nM, respectively. CC-115 blocks bothmTORC1 and mTORC2 signaling.Compound 401 is a synthetic inhibitor of DNA-PK(IC = 0.28 M) that also targets mTOR but not50PI3K in vitro.Purity: 98.23%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mgPurity: 99.97%Clinical Data: No Development Reported

13、Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/dna-pk-in-1.html DNA-PK-IN-1 HYPERLINK https:/www.MedChemE/dna-pk-in-1.html HYPERLINK https:/www.MedChemE/dna-pk-in-2.html DNA-PK-IN-2Cat. No.: HY-142943 Cat. No.: HY-142944DNA-PK-IN-1 is a potent inhibitor of DNA-PK.DNA-depe

14、ndent protein kinase (DNA-PK) is a DNA-PKenzyme complex composed of Ku70/Ku80 heterodimerand DNA-dependent protein kinase catalytic subunit(DNA-PKcs).DNA-PK-IN-2 is a potent inhibitor of DNA-PK.DNA-dependent protein kinase (DNA-PK) is a DNA-PKenzyme complex composed of Ku70/Ku80 heterodimerand DNA-d

15、ependent protein kinase catalytic subunit(DNA-PKcs).Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/dna-pk-in-3.html DNA-PK-IN-3 HYPERLINK https:/www.MedChemE/dna-pk-in-3.html HYPERLINK h

16、ttps:/www.MedChemE/dna-pk-in-4.html DNA-PK-IN-4Cat. No.: HY-144036 Cat. No.: HY-144037DNA-PK-IN-3 is a potent inhibitor of DNA-PK.DNA-PK-IN-3 synergistically enhances the effect ofradiotherapy and chemotherapy and effectivelyinhibits tumor growth. DNA-PK-IN-3 alsoeffectively reduces the damage to no

17、rmal cells andreducing side effects.DNA-PK-IN-4 is a potent inhibitor of DNA-PK.DNA-PK-IN-4 is a imidazolinone derivativecompound. DNA-PK-IN-4 inhibits DNA-PKcs activity,thus greatly reducing tumor DNA repair andinducing cells to enter the apoptotic program.Purity: 98%Clinical Data: No Development R

18、eportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg2 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/dna-pk-in-5.html DNA-PK-IN-5 HYPERLINK https:/www.MedChemE/dna-pk-in-5.html HYPERLINK https:/www.MedChemE/dna-pk-in-6.html

19、DNA-PK-IN-6Cat. No.: HY-144038 Cat. No.: HY-144039DNA-PK-IN-5 is a potent inhibitor of DNA-PK.DNA-PK-IN-5 inhibits DNA-PKcs activity, thusgreatly reducing tumor DNA repair and inducingcells to enter the apoptotic program.DNA-PK-IN-6 is a potent inhibitor of DNA-PK.DNA-PK-IN-6 inhibits DNA-PKcs activ

20、ity, thusgreatly reducing tumor DNA repair and inducingcells to enter the apoptotic program.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/dna-pk-in-7.html DNA-PK-IN-7 HYPERLINK https:/w

21、ww.MedChemE/dna-pk-in-7.html HYPERLINK https:/www.MedChemE/etp-45658.html ETP-45658Cat. No.: HY-142471 Cat. No.: HY-110109DNA-PK-IN-7 is a potent DNA-PK inhibitor with anIC of 1 nM (WO2021104277A1, compound 5).50ETP-45658 is a potent PI3K inhibitor, with IC s of5022.0 nM, 39.8 nM, 129.0 nM and 717.3

22、 nM for PI3K,PI3K, PI3K and PI3K, respectively. ETP-45658 alsocan inhibit DNA-PK (IC50=70.6 nM) and mTOR(IC =152.0 nM). ETP-45658 can be used for the50research of cancer.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.05%Clinical Data: No Development ReportedSize: 5 mg, 1

23、0 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/ku-0060648.html KU-0060648Cat. No.: HY-13431 HYPERLINK https:/www.MedChemE/KU-57788.html KU-57788(NU7441) Cat. No.: HY-11006KU-0060648 is a dual inhibitor of PI3K and DNA-PKwith IC s of 4 nM, 0.5 nM, 0.1 nM, 0.594 nM and508.6 nM for PI3K, PI3K, PI3K,

24、 PI3K and DNA-PK,respectively.KU-57788 (NU7441) is a highly potent and selectiveDNA-PK inhibitor with an IC of 14 nM. KU-5778850is an NHEJ pathway inhibitor. KU-57788 alsoinhibits PI3K and mTOR with IC s of 5.0 and 1.750M, respectively.Purity: 99.39%Clinical Data: No Development ReportedSize: 5 mgPu

25、rity: 99.35%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/LTURM34.html LTURM34 HYPERLINK https:/www.MedChemE/LTURM34.html HYPERLINK https:/www.MedChemE/LY294002.html LY294002Cat. No.: HY-101667 Cat. No.: HY-10108LTURM34 is a specific

26、 DNA-PK inhibitor (IC =3450nM). LTURM34 exhibits 170-fold selectivity forDNA-PK over PI3K. LTURM34 shows potentantiproliferative activity in a wide range oftumor cell lines.LY294002 is a broad-spectrum inhibitor of PI3K withIC s of 0.5, 0.57, and 0.97 M for , andPI3K, respectively. LY294002 also inh

27、ibits CK250 PI3K PI3Kwith an IC of 98 nM.50Purity: 99.24%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.95%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10 mg, 50 mg, 100 mg, 200 mg, 500 mg HYPERLINK https:/www.MedChemE/NU-7026.html NU HYPERLIN

28、K https:/www.MedChemE/NU-7026.html HYPERLINK https:/www.MedChemE/NU-7026.html 7026 HYPERLINK https:/www.MedChemE/NU-7026.html HYPERLINK https:/www.MedChemE/nu5455.html NU5455(LY293646) Cat. No.: HY-15719Cat. No.: HY-145427NU 7026 (LY293646) is a novel specific DNA-PKinhibitor with IC50 of 0.23 M, al

29、so inhibits PI3Kwith IC of 13 M.50NU5455 is a potent, selective, and orally activeinhibitor of DNA-PKcs. NU5455 administrationincreases both the efficacy and the toxicity of aparenterally administered topoisomerase inhibitor.Purity: 99.92%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 50 m

30、gPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgwww.MedChemE 3 HYPERLINK https:/www.MedChemE/pi-103.html PI-103 HYPERLINK https:/www.MedChemE/pi-103.html HYPERLINK https:/www.MedChemE/PI-103-Hydrochloride.html PI-103 HYPERLINK https:/www.MedChemE/PI-103-Hydrochloride.html HYPERLINK

31、 https:/www.MedChemE/PI-103-Hydrochloride.html HydrochlorideCat. No.: HY-10115 Cat. No.: HY-10115API-103 is a potent PI3K and mTOR inhibitor withIC s of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 8350nM for p110, p110, p110, p110, mTORC1,and mTORC2. PI-103 also inhibits DNA-PK withan IC50 of 2 nM. PI-10

32、3 induces autophagy.PI-103 Hydrochloride is a dual PI3K and mTORinhibitor with IC s of 8 nM, 88 nM, 48 nM, 15050nM, 20 nM, and 83 nM for p110, p110, p110,p110, mTORC1, and mTORC2. PI-103Hydrochloride also inhibits DNA-PK with an IC50 of2 nM. PI-103 Hydrochloride induces autophagy.Purity: 98.93%Clini

33、cal Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.06%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/pi-103-d8.html PI-103-d8 HYPERLINK https:/www.MedChemE/pi-103-d8.html HYPERLINK https:/www.MedCh

34、emE/pik-75-1.html PIK-75Cat. No.: HY-10115S Cat. No.: HY-107834PI-103-d8 is the deuterium labeled PI-103. PI-103is a potent PI3K and mTOR inhibitor with IC s50of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 83 nMfor p110, p110, p110, p110, mTORC1, andmTORC2. PI-103 also inhibits DNA-PK with anIC50 of 2 nM

35、. PI-103 induces autophagy.PIK-75 is a reversible DNA-PK and p110-selectiveinhibitor, which inhibits DNA-PK, p110 and p110with IC s of 2, 5.8 and 76 nM, respectively.50PIK-75 inhibits p110 200-fold more potentlythan p110 (IC50=1.3 M). PIK-75 induces apoptosis.Purity: 98%Clinical Data: No Development

36、 ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/pik-75.html PIK-75 HYPERLINK https:/www.MedChemE/pik-75.html HYPERLINK https:/www.MedChemE/pik-75.html hydrochloride HYPERLINK https:/www.MedChemE/pik-75.html HYPERLINK https:/www

37、.MedChemE/PIK-90.html PIK-90Cat. No.: HY-13281 Cat. No.: HY-12030PIK-75 hydrochloride is a reversible DNA-PK andp110-selective inhibitor, which inhibits DNA-PK,p110 and p110 with IC s of 2, 5.8 and 76 nM,50respectively. PIK-75 hydrochloride inhibits p110200-fold more potently than p110 (IC =1.350M).

38、 PIK-75 hydrochloride induces apoptosis.PIK-90 is a DNA-PK and PI3K inhibitor, whichinhibits p110, p110 and DNA-PK with IC s of5011, 18 and 13 nM, respectively.Purity: 99.72%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10 mg, 50 mg, 100 mgPurity: 99.70%Clinical Data: No Development Report

39、edSize: 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/LY3023414.html Samotolisib HYPERLINK https:/www.MedChemE/LY3023414.html HYPERLINK https:/www.MedChemE/SF2523.html SF2523(LY3023414) Cat. No.: HY-12513Cat. No.: HY-101146Samotolisib (LY3023414) potently and selectivelyinhibits class I P

40、I3K isoforms, DNA-PK, andmTORC1/2 with IC s of 6.07 nM, 77.6 nM, 38 nM,5023.8 nM, 4.24 nM and 165 nM for PI3K, PI3K,PI3K, PI3K, DNA-PK and mTOR, respectively.SF2523 is a highly selective and potent inhibitorof PI3K with IC s of 34 nM, 158 nM, 9 nM, 241 nM50and 280 nM for PI3K, PI3K, DNA-PK, BRD4 and mTOR,respectively.Purity: 99.42%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 97.32%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/stl127705.html STL127705 HYPERLINK https:/www.MedChemE/s