DYRK-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/DYRK.html DYRKDual specificity tyrosine phosphorylation regulated kinase; Dual specificity tyrosine regulated kinaseDYRKs (dual-specificity tyrosine-regulated kinases; dual-specificity tyrosinephosphorylation-regulated kinases) comprise a family of protein kina

2、ses within the CMGC group of theeukaryotic kinome. DYRKs contain five members in humans that are clustered into two classes based ontheir phylogenetic relationships: class I DYRKs, DYRK1A and DYRK1B and class II DYRKs, DYRK2, DYRK3, and DYRK4.DYRK kinases are “dual specificity” kinases, as they can

3、phosphorylate both tyrosine (Y) and serine/threonine (S/T) residues,although Y-phosphorylation is limited to their autophosphorylation activity. DYRK kinases phosphorylate a broad set of substratesthat are involved in a wide range of cellular processes, and they are thought to fulfill essential biol

4、ogical functions both duringdevelopment and in maintaining homeostasis during the adult life. Consequently, the aberrant regulation or expression of DYRKkinases has been associated with several human pathologies, including cancer.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/DYRK.html DYRK HY

5、PERLINK https:/www.MedChemE/Targets/DYRK.html HYPERLINK https:/www.MedChemE/Targets/DYRK.html Inhibitors HYPERLINK https:/www.MedChemE/arn25068.html ARN25068 HYPERLINK https:/www.MedChemE/arn25068.html HYPERLINK https:/www.MedChemE/az-dyrk1b-33.html AZ-Dyrk1B-33Cat. No.: HY-144290 Cat. No.: HY-11739

6、1ARN25068 is a sub-micromolar inhibitor of thethree protein kinases, GSK-3, FYN and DYRK1Ato tackle tau hyperphosphorylation.AZ-Dyrk1B-33 is a potent and selective Dyrk1Bkinase inhibitor, with an IC of 7 nM.50Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.95%Clinical Dat

7、a: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/AZ191.html AZ191 HYPERLINK https:/www.MedChemE/AZ191.html HYPERLINK https:/www.MedChemE/ck2-erk8-in-1.html CK2/ERK8-IN-1Cat. No.: HY-12277 Cat. No.: HY-135906AZ191 is a potent inhibitor that selectivelyinhibits DYRK1B with IC o

8、f 17 nM.50CK2/ERK8-IN-1 is a dual casein kinase 2 (CK2) (Kof 0.25 M) and ERK8 (MAPK15, ERK7) inhibitoriwith IC s of 0.50 M. CK2/ERK8-IN-1 also binds to50PIM1, HIPK2 (homeodomain-interacting proteinkinase 2), and DYRK1A with Ks of 8.65 M, 15.25iM, and 11.9 M, respectively.Purity: 99.98%Clinical Data:

9、 No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.82%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/clk-in-t3.html CLK-IN-T3 HYPERLINK https:/www.MedChemE/clk-in-t3.html HYPERLINK https:/www.MedChemE/dyrk1-in-1.

10、html DYRK1-IN-1Cat. No.: HY-115470 Cat. No.: HY-132308CLK-IN-T3 is a high potent, selective, and stableCDC-like kinase (CLK) inhibitor with IC s of 0.6750nM, 15 nM, and 110 nM for CLK1, CLK2, and CLK3protein kinases, respectively. CLK-IN-T3 hasanti-cancer activity.DYRK1-IN-1 is a highly selective an

11、dligand-efficient DYRK1A inhibitor. DYRK1-IN-1inhibits DYRK1A phosphorylation activity with anIC value of 220 nM. DYRK1-IN-1 can be used for50the research of central nervous system penetrantDYRK1A chemical probe.Purity: 98.40%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg

12、, 50 mg, 100 mgPurity: 99.62%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/dyrk1a-in-1.html Dyrk1A-IN-1 HYPERLINK https:/www.MedChemE/dyrk1a-in-1.html HYPERLINK https:/www.MedChemE/dyrks-in-1.html DYRKs-IN-1Cat. No.: HY-139830 Cat. No.: H

13、Y-128758Dyrk1A-IN-1 is a triple inhibitor of Dyrk1A kinaseactivity (IC = 119 nM) and the aggregation of50tau and -syn oligomers.DYRKs-IN-1 is a potent DYRKs (Dual-specificitytyrosine-phosphorylation-regulated kinases)inhibitor with IC s of 5 nM and 8 nM for DYRK1A50and DYRK1B, respectively. DYRKs-IN

14、-1 has antitumoractivity.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/dyrks-in-1-hydrochloride.html DYRKs-IN-1 HYPERLINK https:/www.MedChemE/dyrks-in-1-hydrochloride.html HYPERLINK htt

15、ps:/www.MedChemE/dyrks-in-1-hydrochloride.html hydrochloride HYPERLINK https:/www.MedChemE/dyrks-in-1-hydrochloride.html HYPERLINK https:/www.MedChemE/dyrks-in-2.html DYRKs-IN-2Cat. No.: HY-128758A Cat. No.: HY-128759DYRKs-IN-1 hydrochloride is a potent DYRKs(Dual-specificitytyrosine-phosphorylation

16、-regulated kinases)inhibitor with IC s of 5 nM and 8 nM for DYRK1A50and DYRK1B, respectively. DYRKs-IN-1 hydrochloridehas antitumor activity.DYRKs-IN-2 (Example 132) is a potent DYRKsinhibitor with IC s of 30.6 nM and 12.8 nM for50DYRK1B and DYRK1A, respectively. DYRKs-IN-2 hasantitumor activity.Pur

17、ity: 99.70%Clinical Data: No Development ReportedSize: 5 mg, 10 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/eht-1610.html EHT HYPERLINK https:/www.MedChemE/eht-1610.html HYPERLINK https:/w

18、ww.MedChemE/eht-1610.html 1610 HYPERLINK https:/www.MedChemE/eht-1610.html HYPERLINK https:/www.MedChemE/eht-5372.html EHT HYPERLINK https:/www.MedChemE/eht-5372.html HYPERLINK https:/www.MedChemE/eht-5372.html 5372Cat. No.: HY-111380 Cat. No.: HY-111379EHT 1610 is a strong inhibitor of DYRKs family

19、kinases, with IC s of 0.36, 0.59 nM for DYRK1A50and DYRK1B, respectively.EHT 5372 is a highly potent and selectiveinhibitor of DYRKs family kinases with IC s of500.22, 0.28, 10.8, 93.2, 22.8, 88.8, 59.0, 7.44,221 nM for DYRK1A, DYRK1B , DYRK2 DYRK3 CLK1,CLK2, CLK4, GSK-3, GSK-3.Purity: 98.07%Clinica

20、l Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/gnf2133.html GNF2133 HYPERLINK https:/www.MedChemE/gnf2133.html HYPERLINK https:/www.MedChemE/gnf4877.html GNF4

21、877Cat. No.: HY-142295 Cat. No.: HY-129492GNF2133 hydrochloride is a potent, selective andorally active DYRK1A inhibitor with IC s of500.0062, 50 M for DYRK1A and GSK3,respectively. GNF2133 hydrochloride shows goodproliferation potency and efficacy on rat andhuman primary -cell.GNF4877 is a potent D

22、YRK1A and GSK3 inhibitorwith IC s of 6nM and 16nM, respectively, which50leads to blockade of nuclear factor of activatedT-cells (NFATc) nuclear export and increased-cell proliferation (EC of 0.66M for mouse50 (R7T1) cells).Purity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50

23、 mg, 100 mgPurity: 98.85%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg HYPERLINK https:/www.MedChemE/gsk-626616.html GSK-626616Cat. No.: HY-105309 HYPERLINK https:/www.MedChemE/harmine-hydrochloride.html Harmine HYPERLINK https:/www.MedChemE/harmine-hydrochloride.html HYPERLI

24、NK https:/www.MedChemE/harmine-hydrochloride.html hydrochloride(Telepathine hydrochloride) Cat. No.: HY-N0737GSK-626616 is a potent, orally bioavailableinhibitor of DYRK3 (IC =0.7 nM). GSK-62661650inhibits other members of the DYRK family (e.g.,DYRK1A and DYRK2) with similar potency, which is apoten

25、tial therapy for the treatment of anemia.Harmine Hydrochloride (Telepathine Hydrochloride)is a natural DYRK inhibitor with anticancer andanti-inflammatory activities. Harmine has a highaffinity of 5-HT serotonin receptor, with an2AK of 397 nM.iPurity: 99.68%Clinical Data: Phase 1Size: 10 mM 1 mL, 5

26、mg, 10 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 20 mg HYPERLINK https:/www.MedChemE/haspin-in-1.html Haspin-IN-1 HYPERLINK https:/www.MedChemE/haspin-in-1.html HYPERLINK https:/www.MedChemE/haspin-in-2.html Haspin-IN-2Cat. No.: HY-146586 Cat. No.: HY-14658

27、7Haspin-IN-1 (compound 2a) is a haspin inhibitorwith an IC of 119 nM. Haspin-IN-1 also inbibits50CLK1 and DYRK1A with IC s of 221 nM and 916.350nM, respectively.Haspin-IN-2 (compound 4) is a potent and selectivehaspin inhibitor with an IC of 50 nM. Haspin-IN-150also inbibits CLK1 and DYRK1A with IC

28、s of 44550nM and 917 nM, respectively.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/ID-8.html ID-8 HYPERLINK https:/www.MedChemE/ID-8.html HYPERLINK https:/www.MedChemE/indy.html INDYCa

29、t. No.: HY-15838 Cat. No.: HY-108476ID-8 is an inhibitor of dual-specificity tyrosinephosphorylation-regulated kinase (DYRK). ID-8sustains embryonic stem cell (ESC) self-renewaland pluripotency. ID-8 enhances Wnt-mediated hESCsurvival and proliferation via inhibition ofDYRKs.INDY is a potent and ATP

30、-competitive Dyrk1A andDyrk1B inhibitor with IC s of 0.24 M and 0.2350M, respectively. INDY binds in the ATP pocket ofthe enzyme and has a K value of 0.18 M foriDyrk1A.Purity: 99.16%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.0%Clinical Data: No Devel

31、opment ReportedSize: 5 mg, 10 mgwww.MedChemE 3 HYPERLINK https:/www.MedChemE/jh-xiv-68-3.html JH-XIV-68-3 HYPERLINK https:/www.MedChemE/jh-xiv-68-3.html HYPERLINK https:/www.MedChemE/jh-xvii-10.html JH-XVII-10Cat. No.: HY-144617 Cat. No.: HY-144614JH-XIV-68-3 is a selective macrocyclic inhibitorof D

32、YRK1A/B. JH-XIV-68-3 displays selectivity forDYRK1A and close family member DYRK1B inbiochemical and cellular assays. JH-XIV-68-3demonstrates antitumor efficacy in head and necksquamous cell carcinoma (HNSCC) cell lines.JH-XVII-10 is a potent, selective and orallyactive DYRK1A and DYRK1B inhibitor w

33、ith IC s of503 nM and 5 nM for DYRK1A and DYRK1B,respectively. JH-XVII-10 shows antitumor efficacyin neck squamous cell carcinoma (HNSCC) celllines.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.

34、MedChemE/kh-cb20.html KH-CB20 HYPERLINK https:/www.MedChemE/kh-cb20.html HYPERLINK https:/www.MedChemE/LDN-192960.html LDN-192960Cat. No.: HY-12828A Cat. No.: HY-13455KH-CB20, an E/Z mixture, is a potent and selectiveinhibitor of CLK1 and the closely related isoformCLK4, with an IC of 16.5 nM for .

35、KH-CB20can also inhibit DYRK1A (IC =57.8 nM) and50 CLK150 CLK3(IC =488 nM).50LDN-192960 is an inhibitor of Haspin andDual-specificity Tyrosine-regulated Kinase 2(DYRK2) with IC s of 10 nM and 48 nM,50respectively.Purity: 99.66%Clinical Data: No Development ReportedSize: 1 mg, 5 mg, 10 mgPurity: 99.5

36、6%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg HYPERLINK https:/www.MedChemE/ldn-192960-hydrochloride.html LDN-192960 HYPERLINK https:/www.MedChemE/ldn-192960-hydrochloride.html HYPERLINK https:/www.MedChemE/ldn-192960-hydrochloride.html hydrochloride HYPERLINK https:/www.MedC

37、hemE/ldn-192960-hydrochloride.html HYPERLINK https:/www.MedChemE/ldn-209929-dihydrochloride.html LDN-209929 HYPERLINK https:/www.MedChemE/ldn-209929-dihydrochloride.html HYPERLINK https:/www.MedChemE/ldn-209929-dihydrochloride.html dihydrochlorideCat. No.: HY-13455A Cat. No.: HY-110320LDN-192960 hyd

38、rochloride is an inhibitor of Haspinand Dual-specificity Tyrosine-regulated Kinase 2(DYRK2) with IC s of 10 nM and 48 nM,50respectively.LDN-209929 dihydrochloride is a potent andselective haspin kinase inhibitor (IC =55 nM)50with180-fold selectivity verses DYRK2 (IC =9.950M). LDN-209929 is a optimiz

39、ed analogue ofLDN-192960 (HY-13455).Purity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mgPurity: 98.0%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/leucettine-l41.html Leucettine HYPERLINK https:/www.MedChemE/leucettine-l41.html HYPER

40、LINK https:/www.MedChemE/leucettine-l41.html L41 HYPERLINK https:/www.MedChemE/leucettine-l41.html HYPERLINK https:/www.MedChemE/mbm-55s.html MBM-55SCat. No.: HY-117049 Cat. No.: HY-101029ALeucettine L41 is a potent inhibitor ofdual-specificity tyrosine phosphorylation-regulatedkinase 1A (DYRK1A), D

41、YRK2, CDC-like kinase 1(CLK1), and CLK3 (IC s = 0.04, 0.035, 0.015, and504.5 M, respectively).MBM-55S is a potent NIMA-related kinase 2(Nek2) inhibitor with an IC of 1 nM. MBM-55S50shows a 20-fold or greater selectivity in mostkinases with the exception of RSK1 (IC =5.4 nM)50and DYRK1a (IC =6.5 nM).

42、50Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/Mirk-IN-1.html Mirk-IN-1 HYPERLINK https:/www.MedChemE/Mirk-IN-1.html HYPERLINK https:/www.MedChemE/Protein_kinase_inhibitors_1.html Prot

43、ein HYPERLINK https:/www.MedChemE/Protein_kinase_inhibitors_1.html HYPERLINK https:/www.MedChemE/Protein_kinase_inhibitors_1.html kinase HYPERLINK https:/www.MedChemE/Protein_kinase_inhibitors_1.html HYPERLINK https:/www.MedChemE/Protein_kinase_inhibitors_1.html inhibitors HYPERLINK https:/www.MedCh

44、emE/Protein_kinase_inhibitors_1.html HYPERLINK https:/www.MedChemE/Protein_kinase_inhibitors_1.html 1(Dyrk1B/A-IN-1) Cat. No.: HY-12838Cat. No.: HY-U00439Mirk-IN-1 is a potent inhibitor of Dyrk1B(Mirkkianse) and Dyrk1A with IC50 of 6848 nM and 228nM respectively. IC50 value: 6848/228 nM(Dyrk1B/Dyrk1A) Target: Dyrk inhibitor Mirk-IN-1had an EC50 of 1.9 0.2 mmol/L on SW620 cells.Protein kinase inhibitors 1 is a novel inhibitorof HIPK2 with an IC50 of 74 nM and Kd of 9.5 nM.Purity: 99.53%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10 mg, 50 mgPu