GSK1292263_1032823-75-8_CoA_MedChemExpress

Product Name:K145

CAS No.: 1309444-75-4

Cat. No.:HY-15779Product Data Sheet

MWt:348.46

Formula:C18H24N2O3S

Purity :>98%

Solubility:

DMSOy

Mechanisms:

Biological Activity:

K145isaselectiveSphK2inhibitorwithanIC50of430±006MwhilenoinhibitionofSphK1at

Pathways:Others; Target:SPHK

K145 is a selective SphK2 inhibitor with an IC50 of 4.30±0.06 μM , while no inhibition of SphK1 at

concentrations up to 10 μM.

IC50 value: 4.3 uM [1]

Target: SphK2

in vitro: K145 inhibited the activity of SphK2 in a dose-dependent manner with an IC50 of 4.30±0.06

uM , while no inhibition of SphK1 at concentrations up to 10 uM was observed. Lineweaver-Burk

analysis revealed a Ki of 6.4±0.7 uM for SphK2 and indicated that K145 is a substrate competitive

inhibitor (with sphingosine). K145 accumulates in U937 cells, suppresses the S1P level, and inhibits

Inhibitors, Agonists, Screening Data SheetBIOLOGICAL ACTIVITY: EPZ015866 (GSK591) is a potent selective inhibitor of the arginine methyltransferase PRMT5. It maintained excellent selectivity againstother PMT enzymes observed with EPZ015666 [1].IC50:61 nM–904 nM in Maver–1 cells [2]target: PRMT5in vitro: A375 cells treated for 18 h with 1 μM EPZ015666 showed stabilization of PRMT5 in cellular thermal shift analysis in whole–celllysates. [2]In vivo: EPZ015666 or vehicle (0.5% methylcellulose in water) was administered orally BID at a dose volume of 10 mL/kg for 21 d(Granta–519 was dosed for 18 d). [2]References: [1]. [1] Kenneth W. Duncan et al. Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666. ACS Med. Chem. Lett.,2016, 7 (2), pp 162–166.[2]. [2] Elayne Chan–Penebre et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nature Chemical Biology 11, 2015,432–437Product Name:EPZ015866Cat. No.:HY-100235CAS No.:1616391-87-7Molecular Formula:C22H28N4O2Molecular Weight:380.48Target:Histone MethyltransferasePathway:EpigeneticsSolubility:10 mM in DMSO

Inhibitors, Agonists, Screening Data Sheet

BIOLOGICAL ACTIVITY: IPI549 is a potent and selective PI3Kγ Inhibitor with IC50 of 16 nM.IC50 & Target: IC50: 16 nM (PI3Kγ), 3.2 μM (PI3Kα), 3.5 μM (PI3Kβ), >8.4 μM (PI3Kδ)[1]In Vitro: IPI–549 inhibits PI3Kγ with IC50 of 16 nM, with >100–fold selectivity over other lipid and protein kinases (PI3Kα IC50=3.2μM, PI3Kβ IC50=3.5 μM, PI3Kδ IC50>8.4 μM). IPI549 is evaluated for activity across all Class I PI3K isoforms. The binding affinity ofIPI549 for PI3K–γ is determined by measuring the individual rates constants and for PI3K–α, β and δ using equilibrium fluorescenttitration. IPI549 is found to be a remarkably tight binder to PI3Kγ with a Kd of 290 pM and >58–fold weaker affinity for otherClass I PI3K isoforms (PI3Kα Kd=17 nM, PI3Kβ Kd=82 nM, PI3Kδ Kd=23 M). In PI3K–α, –β, –γ, and –δ dependent cellularphospho–AKT assays, IPI549 demonstrates excellent PI3K–γ potency (IC50=1.2 nM) and selectivity against other Class I PI3Kisoforms (>146–fold). Cellular IC50s for Class I PI3Kα (250 nM), PI3Kβ (240 nM), PI3Kγ (1.2 nM), PI3Kδ (180 nM) are determined inSKOV–3, 786–O, RAW 264.7, and RAJI cells, respectively, by monitoring inhibition of pAKT S473 by ELISA. Furthermore, IPI549 dosedependently inhibits PI3Kγ dependent bone marrow–derived macrophage (BMDM) migration. IPI549 is also found to be selectiveagainst a panel of 80 GPCRs, ion channels, and transporters at 10 μM[1].In Vivo: IPI–549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K–γ mediated neutrophil migration.In vivo (mice, rats, dog, and monkeys), IPI–549 has excellent oral bioavailability, low clearance, and distributed into tissues with amean volume of distribution of 1.2 L/kg. Overall, IPI–549 has a favorable pharmacokinetic profile to allow potent and selectiveinhibition of PI3K–γ in vivo. The t1/2 of IPI–549 for mouse, rat, dog and monkey is 3.2, 4.4, 6.7 and 4.3 h, respectively. IPI–549significantly reduces neutrophil migration in a dose dependent manner in this model when administered orally at all of the testeddoses[1].References: [1]. Evans CA, et al. Discovery of a Selective Phosphoinositide–3–Kinase (PI3K)–γ Inhibitor (IPI–549) as an Immuno–Oncology Clinical Candidate. ACS MedChem Lett. 2016 Jul 22;7(9):862–7.Product Name:IPI549Cat. No.:HY-100716CAS No.:1693758-51-8Molecular Formula:C30H24N8O2Molecular Weight:528.56Target:PI3KPathway:PI3K/Akt/mTORSolubility:

Inhibitors, Agonists, Screening Data SheetBIOLOGICAL ACTIVITY: PYZD–4409 is a novel small molecule inhibitor of Ubiquitin–activating enzyme UBA1/E1 enzyme with an IC50 of 20 uM (cell–freeenzymatic assay).IC50 Value: 20 uM (cell–free enzymatic assay) [1]Target: E1 enzyme (Ubiquitin–activating enzyme)in vitro: PYZD–4409 inhibited the ATP–dependent activation of ubiquitin and subsequent transfer of the activated ubiquitin from theE1 to the common human E2 enzyme UBE2E2 in a gel–based assay. The IC50 of inhibition was estimated to be 20μM in a cell–freeenzymatic assay. Suggesting specificity of PYZD–4409 for the E1 enzyme, the compound had no effect on unrelated enzymes such asα–Mannosidase II glycosylation enzyme or Luciferase at concentrations up to 100μM (data not shown). It also did not inhibit thesummo E1, Uba2, at concentrations up to 100μM. In 5 of 8 leukemia and myeloma cell lines, PYZD–4409 induced cell death with aLD50 less than 10μM. Myeloma cell lines were particularly sensitive to E1 inhibition because PYZD–4409 induced cell death with 3 of 4myeloma cell lines (ie, LP1, KMS11, and U226) having an LD50 of 3μM or less. In contrast, solid tumor cell lines were less sensitive withan LD50 of approximately 15 to 20μM [1].in vivo: SCID mice were injected subcutaneously with MDAY–D2 murine leukemia cells and then treated with PYZD–4409 (10 mg/kg)or buffer control intraperitoneally daily on alternate days over 8 days. Sixteen days after tumor implantation, the mice were killed, andthe tumors excised and weighed. Compared with control–treated mice, treatment with PYZD–4409 delayed tumor growth anddecreased tumor weight without untoward toxicity. Inhibition of the E1 can achieve an antitumor effect in vivo [1].PROTOCOL (Extracted from published papers and Only for reference) Enzyme assay [1]To determine the E1 enzymatic activity in vitro, GST–tagged E1 and fluorescein–tagged ubiquitin (1μM) were incubated with orwithout increasing concentrations of PYZD–4409 or PYZDmut in 10 μL of the above–mentioned reaction buffer for 30 minutes at 37°C. The products were then fractionated on 4% to 20% gradient sodium dodecyl sulfate–polyacrylamide gel electrophoresis(SDS–PAGE). Formation of E1–Ub conjugate was assessed by visualization of fluorescent signals with the use of a Typhoon variableimager (Amersham Biosciences).References: [1]. Xu GW, et al. The ubiquitin–activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. Blood. 2010 Mar 18;115(11):2251–9.Product Name:PYZD–4409Cat. No.:HY-13297CAS No.:423148-78-1Molecular Formula:C14H7ClFN3O5Molecular Weight:351.67Target:E1/E2/E3 EnzymePathway:Metabolic Enzyme/ProteaseSolubility:DMSO: ≥ 35 mg/Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852,