SPHK-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/SPHK.html SphKSphingosine kinaseSphingosine kinase (SphK1 and SphK2) is a lipid enzyme that catalyses the phosphorylation of sphingosine to form sphingosine1-phosphate (S1P). Two isoforms of SphK are found in mammalian organisms, SphK1 and SphK2. SphK1 is found

2、 primarily in thecytoplasm and the plasma membrane of erythrocyte, endothelial and mast cells. SphK2 is larger and localized to the endoplasmicreticulum, nucleus, and mitochondria.S1P binds to five different plasma membrane sphingosine 1-phosphate receptors (S1P ) and can regulate intracellular targ

3、et1-5proteins. S1P has a wide range of biological functions including promotion of cellular proliferation and survival, immune celltrafficking, stimulation of angiogenesis, and regulation of vascular integrity. Accumulation of S1P has been linked to thedevelopment/progression of cancer and various o

4、ther diseases including, but not limited to, asthma, inflammatory bowel disease,rheumatoid arthritis, and diabetic nephropathy. Thus, the biosynthetic route to S1P is a logical target for drug discovery. SphK1 andSphK2 isozymes are also recognized therapeutic targets.www.MedChemE 1 HYPERLINK https:/

5、www.MedChemE/Targets/SPHK.html SphK HYPERLINK https:/www.MedChemE/Targets/SPHK.html HYPERLINK https:/www.MedChemE/Targets/SPHK.html Inhibitors HYPERLINK https:/www.MedChemE/Targets/SPHK.html HYPERLINK https:/www.MedChemE/Targets/SPHK.html & HYPERLINK https:/www.MedChemE/Targets/SPHK.html HYPERLINK h

6、ttps:/www.MedChemE/Targets/SPHK.html Activators HYPERLINK https:/www.MedChemE/cay10621.html CAY10621(SKI 5C) Cat. No.: HY-117563 HYPERLINK https:/www.MedChemE/k145.html K145Cat. No.: HY-15779CAY10621 (SKI 5C; compound 5c) is a specificsphingosine kinase 1 (SPHK1) inhibitor with anIC of 3.3 M. CAY106

7、21 is low toxic toward50cells. CAY10621 has the potential for resistant cancer tumors research.K145 is a selective, substrate-competitive andorally active SphK2 inhibitor with an IC of 4.350M and a K of 6.4 M. K145 is inactive againstiSphK1 and other protein kinases. K145 induces cellapoptosis and h

8、as potently antitumor activity.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/k145-hydrochloride.html K145 HYPERLINK https:/www.MedChemE/k145-hydrochloride.html HYPERLINK https:/www.MedC

9、hemE/k145-hydrochloride.html hydrochloride HYPERLINK https:/www.MedChemE/k145-hydrochloride.html HYPERLINK https:/www.MedChemE/k6pc-5.html K6PC-5Cat. No.: HY-15779A Cat. No.: HY-124042K145 hydrochloride is a selective,substrate-competitive and orally active SphK2inhibitor with an IC50 of 4.3 M and a

10、 Ki of 6.4M. K145 hydrochloride is inactive against SphK1and other protein kinases.K6PC-5, a synthetic ceramide derivative,is adirect sphingosine kinase 1(SPHK1) activator andelicites a rapid transient increase inintracellular calcium levels.Purity: 99.34%Clinical Data: No Development ReportedSize:

11、10 mM 1 mL, 5 mg, 10 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/MHP.html MHP(Methyl caprooyl tyrosinate) Cat. No.: HY-101572 HYPERLINK https:/www.MedChemE/MP-A08.html MP-A08Cat. No.: HY-19794MHP (Methyl capr

12、ooyl tyrosinate) is an activatorof sphingosine kinase (SPHK1), and significantlystimulates CAMP mRNA and protein production. MHP(Methyl caprooyl tyrosinate) enhancesantimicrobial defense and innate immunity.MP-A08 is a highly selective ATP competitivesphingosine kinase (SPHK1) inhibitor that targets

13、both SphK1 and SphK2 with Ki values of 6.9 0.8M and 27 3 M, respectively.Purity: 98.54%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 25 mgPurity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/n

14、-n-dimethylsphingosine.html N,N-Dimethylsphingosine HYPERLINK https:/www.MedChemE/n-n-dimethylsphingosine.html HYPERLINK https:/www.MedChemE/ABC294640.html OpaganibCat. No.: HY-108491(ABC294640) Cat. No.: HY-16015N,N-Dimethylsphingosine is a potent inhbitor ofSphK (sphingosine kinase) as an endogeno

15、usmetabolite of sphingosine produced in varioustissues and tumor cell lines.Opaganib (ABC294640) is a selective, competitivesphingosine kinase 2 (SK2) inhibitor with K ofi9.8 M.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.68%Clinical Data: No Development ReportedSize:

16、10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/Peretinoin.html Peretinoin HYPERLINK https:/www.MedChemE/Peretinoin.html HYPERLINK https:/www.MedChemE/PF-543.html PF-543(NIK333) Cat. No.: HY-100008 (Sphingosine Kinase 1 Inhibitor II) Cat. No.: HY-15425Peretinoin is an oral acycl

17、ic retinoid with avitamin A-like structure that targets retinoidnuclear receptors such as retinoid X receptor(RXR) and retinoic acid receptor (RAR).PF-543 (Sphingosine Kinase 1 Inhibitor II) is apotent, selective, reversible andsphingosine-competitive SPHK1 inhibitor with anIC50 of 2 nM and a Ki of

18、3.6 nM. PF-543 is100-fold selectivity for SPHK1 over SPHK2.Purity: 99.79%Clinical Data: LaunchedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 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/PF-543

19、-Citrate.html PF-543 HYPERLINK https:/www.MedChemE/PF-543-Citrate.html HYPERLINK https:/www.MedChemE/PF-543-Citrate.html Citrate(Sphingosine Kinase 1 Inhibitor II Citrate) Cat. No.: HY-15425A HYPERLINK https:/www.MedChemE/pf-543-hydrochloride.html PF-543 HYPERLINK https:/www.MedChemE/pf-543-hydrochl

20、oride.html HYPERLINK https:/www.MedChemE/pf-543-hydrochloride.html hydrochloride(Sphingosine Kinase 1 Inhibitor II hydrochloride) Cat. No.: HY-15425BPF-543 Citrate (Sphingosine Kinase 1 Inhibitor IICitrate) is a potent, selective, reversible andsphingosine-competitive SPHK1 inhibitor with anIC50 of

21、2 nM and a Ki of 3.6 nM. PF-543 Citrate is100-fold selectivity for SPHK1 over SPHK2.PF-543 hydrochloride (Sphingosine Kinase 1Inhibitor II hydrochloride) is a potent,selective, reversible and sphingosine-competitiveSPHK1 IC50 Kiinhibitor with an of 2 nM and a of3.6 nM. PF-543 hydrochloride is 100-fo

22、ldselectivity for SPHK1 over SPHK2.Purity: 98.35%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/Phorbol-12-myristate-13-acetate.html Phorbol HYPERLINK https:/www.MedChem

23、E/Phorbol-12-myristate-13-acetate.html HYPERLINK https:/www.MedChemE/Phorbol-12-myristate-13-acetate.html 12-myristate HYPERLINK https:/www.MedChemE/Phorbol-12-myristate-13-acetate.html HYPERLINK https:/www.MedChemE/Phorbol-12-myristate-13-acetate.html 13-acetate(PMA; TPA; Phorbol myristate acetate)

24、 Cat. No.: HY-18739 HYPERLINK https:/www.MedChemE/sk1-i.html SK1-I(BML-258) Cat. No.: HY-119016Phorbol 12-myristate 13-acetate (PMA), a phorbolester, is a dual SphK and protein kinase C (PKC)activator. Phorbol 12-myristate 13-acetate is aNF-B activator. Phorbol 12-myristate 13-acetateinduces differe

25、ntiation in THP-1 cells.SK1-I (BML-258), an analog of sphingosine, is anisozyme-specific competitive SPHK1 inhibitor witha K value of 10 M. SK1-I shows no activity atiSPHK1 PKC, PKC, PKA, AKT1, ERK1, EGFR, CDK2,IKK or CamK2. SK1-I enhances autophagy and hasantitumor activity.Purity: 99.66%Clinical D

26、ata: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 25 mgPurity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/SK1-IN-1.html SK1-IN-1Cat. No.: HY-101805 HYPERLINK https:/www.MedChemE/sk1-i-hydrochloride.html SK1-I HYPERLIN

27、K https:/www.MedChemE/sk1-i-hydrochloride.html HYPERLINK https:/www.MedChemE/sk1-i-hydrochloride.html hydrochloride(BML-258 hydrochloride) Cat. No.: HY-119016ASK1-IN-1 is a potent sphingosine kinase 1 (SPHK1)inhibitor with an IC of 58 nM.50SK1-I hydrochloride (BML-258 hydrochloride), ananalog of sph

28、ingosine, is an isozyme-specificcompetitive SPHK1 inhibitor with a K value of 10iM. SK1-I hydrochloride shows no activity at SPHK1PKC, PKC, PKA, AKT1, ERK1, EGFR, CDK2, IKK orCamK2.Purity: 98.75%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99

29、.49%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/SKI-II.html SKI HYPERLINK https:/www.MedChemE/SKI-II.html HYPERLINK https:/www.MedChemE/SKI-II.html II HYPERLINK https:/www.MedChemE/SKI-II.html HYPERLINK https:/www.MedChemE/ski-v.html SK

30、I HYPERLINK https:/www.MedChemE/ski-v.html HYPERLINK https:/www.MedChemE/ski-v.html VCat. No.: HY-13822 Cat. No.: HY-12895SKI-II is an oral active and synthetic inhibitorof sphingosine kinase (SK) activity, with IC50values of 78 M and 45 M for SK1 and for SK2,respectively. SKI II causes an irreversi

31、bleinhibition of SK1 by inducing its lysosomal and/orproteasomal degradation.SKI V is a noncompetitive and potent non-lipidsphingosine kinase (SPHK; SK) inhibitor with anIC of 2 M for GST-hSK. SKI V potently inhibits50PI3K with an IC of 6 M for hPI3k. SKI V50decreases formation of the mitogenic seco

32、ndmessenger sphingosine-1-phosphate (S1P).Purity: 99.88%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10 mg, 25 mg, 50 mg, 100 mg, 200 mgPurity: 98.09%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/ski-178.html SKI-178 HYPERLINK https:/www.MedChemE/ski-178.html HYPERLINK https:/www.MedChemE/ski-i.html SKI-ICat. No.: HY-12892 Cat. No.: HY-115735SKI-178 is a potent sphingosine kinase-1 (SphK1)and SphK2 inhibit