BQU57_DataSheet_MedChemExpress

BRD4 degrader AT1Cat. No.:HY-111433

CAS No.:2098836-45-2

Molecular Formula:C₄₈H₅₈ClN₉O₅S₃

Molecular Weight:972.68

Target:Epigenetic Reader Domain; PROTAC

Pathway:Epigenetics; PROTAC

Storage:Please store the product under the recommended conditions in the COA.

Solvent & Solubility

In Vitro10 mM in DMSO

ConcentrationSolventMass1 mg5 mg10 mg

1 mM1.0281 mL5.1404 mL10.2809 mL

5 mM0.2056 mL1.0281 mL2.0562 mLPreparing

Stock Solutions

10 mM0.1028 mL0.5140 mL1.0281 mL

Please refer to the solubility information to select the appropriate solvent.

BIOLOGICAL ACTIVITY

DescriptionBRD4 degrader AT1 is a highly selective Brd4 degrader based on PROTAC technology, with a Kd of 44 nM for Brd4

BD2 in cells.

IC₅₀ & TargetKd: 44 nM (Brd4BD2, cell assay), 38.8 nM (Brd4BD2 QVK, cell assay), 111 nM (Brd2BD1, cell assay), 94 nM (Brd2BD2, cell

Product Name:BIX02189

CAS No.: 1265916-41-3Product Data Sheet

Cat. No.:HY-12056

MWt:440.54

Formula:C27H28N4O2

Purity :

>98%

Solubility:

Mechanisms:

Biological Activity: Pathways:MAPK ; Target:MEK

DMSO

gyBIX02189 is a selective MEK5/ERK5 inhibitor with an IC50 of 59 nM.

References:[1]. Tatake RJ et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun. 2008 Dec 5;377(1):120-5.[2]. Kondo M, Inamura H, Matsumura K, Matsuoka M.Cadmium activates extracellular signal-regulated kinase 5 in HK-2 human renal proximal tubular cells.Biochem Biophys Res Commun. 2012gppy May 11;421(3):490-3. Epub 2012 Apr 10.[3]. Li P, Ma YC, Sheng XY, Dong HT, Han H, Wang J, Xia YY.Cyclic fluid shear stress promotesosteoblastic cells proliferation through ERK5 signaling pathway.Mol Cell Biochem. 2012 May;364(1- 2):321-7.[4]. Gilley R, Lochhead PA, Balmanno K, Oxley D, Clark J, Cook SJ.CDK1, not ERK1/2 or ERK5, is required for mitotic phosphorylation of BIMEL.Cell Signal. 2012 Jan;24(1):170-80. Epub 2011 Sep 8.[5]. Obara Y, Nemoto W, Kohno S, Murata T, Kaneda N, Nakahata N.Basic fibroblast growth factorpromotes...

Inhibitors, Agonists, Screening Data SheetBIOLOGICAL ACTIVITY: P22077 is a potent inhibitor of ubiquitin–specific protease (USP) 7 (EC50=8.6 uM), P22077 also inhibits the closely relateddeubiquitinase (DUB) USP47.IC50 Value: 8.6 uM (EC50) [1]Target: USP7; USP47in vitro: P22077 potently induces apoptosis in NB cells with an intact USP7–HDM2–p53 axis but not in NB cells with mutant p53 orwithout human homolog of MDM2 (HDM2) expression. P22077 stabilized p53 by inducing HDM2 protein degradation in NB cells.P22077 also significantly augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP–16) in NB cells with an intactUSP7–HDM2–p53 axis. Moreover, P22077 was found to be able to sensitize chemoresistant LA–N–6 NB cells to chemotherapy [2].in vivo: In an in vivo orthotopic NB mouse model, P22077 significantly inhibited the xenograft growth of three NB cell lines [2].PROTOCOL (Extracted from published papers and Only for reference) Cell assay [2]Cell viability assays were assessed using the Cell Counting Kit–8 (CCK–8,WST–8[2–(2–methoxy–4–nitrophenyl)–3–(4–nitrophenyl)–5–(2,4–disulfophenyl)–2 H–tetrazolium, monosodium salt]) (DojindoLaboratories, Rockville, MA, USA) following the manufacturer's instructions. Cells were seeded in 96–well flat–bottomed plates at thedensity of 1 × 104 per well. After 24 h of incubation at 37 °C, increasing concentrations of P22077, Dox, VP–16, or their combinationswere added to the wells. Twenty–four hours later, 10 μl of CCK–8 was added into each well and after 1 h of incubation, the absorbancewas measure at 450 nm using the microplate reader. Each experiment was performed in replicates of six. Background reading ofmedia only was used to normalize the results.Animal administration [2]Briefly, 1.5 × 106 human IMR–32, SH–SY5Y, or NGP cells with luciferase expression were surgically injected into the left renal capsuleof 5–week–old female NCR nude mice. IMR–32, SH–SY5Y, and NGP–derived xenografts were allowed to grow for ~2–3 weeks beforerandomizing the mice into a control group and a P22077 treatment group. Each group consisted of three or six mice. Animals weretreated with DMSO or P22077 by intraperitoneal (i.p.) injection every day for 12, 14, or 21 days. At the end of the experiments, all micewere killed. Tumors and the right side control kidneys were resected, weighed, and photographed. All mice were housed in apathogen–free environment and handled in strict accordance to institutional protocol.References: [1]. Altun M, et al. Activity–based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol. 2011 Nov 23;18(11):1401–12.Product Name:P 22077Cat. No.:HY-13865CAS No.:1247819-59-5Molecular Formula:C12H7F2NO3S2Molecular Weight:315.32Target:DeubiquitinasePathway:Cell Cycle/DNA DamageSolubility:10 mM in DMSO

Product Name:R547

CAS No.: 741713-40-6Product Data Sheet

Cat. No.:HY-10014

MWt:441.45

Formula:C18H21F2N5O4S

Purity :

>98%

Solubility:

Mechanisms:

Biological Activity: Pathways:Cell Cycle/DNA Damage; Target:CDKDMSO

gy

R547 is a novel, selective inhibitor of cell cycle and transcriptional cyclin dependent kinases with a

Ki of median 2 nM for CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1.

References:

[1]. DePinto, Wanda et al In vitro and in vivo activity of R547: a potent and selective cyclin-

dependent kinase inhibitor currently in phase I clinical trials Molecular Cancer Therapeutics (2006),

5(11), 2644-2658

[2]. Jones, Clifford D.; Andrews, David M. Imidazole pyrimidine amides as potent, orally bioavailable[]pypy

cyclin-dependent kinase inhibitors Bioorganic & Medicinal Chemistry Letters (2008), 18(24), 6486-

6489