MK-8776 (SCH 900776) - 2mM in DMSO , Serine/threonine-protein kinase Chk1 inhibitor, CAS No.891494-63-6, Serine/threonine-protein kinase Chk1 inhibitor

CAS: 891494-63-6 Cat. No.: M408689 Peso molecular: 376.25 PubChem CID: 46239015

GRADE & PURITY 2mM in DMSO

Synonyms

6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-((R)-piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

MK-8776 (SCH 900776) is a selectiveChk1inhibitor withIC50of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.
In vitro

SCH 900776 is a less potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. SCH 900776 induces a dose-dependent loss of DNA replication capability 24 hours after hydroxyurea exposure. SCH 900776 enhances the γ-H2AX response of hydroxyurea, 5-fluoruracil, and cytarabine. In combination with an antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicative of replication fork collapse and double stranded DNA breaks. Additionally, SCH 900776 suppresses accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Exposure of proliferating WS1 cells to SCH 900776 is associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 following exposure to SCH 900776 as part of a futile cycle, perhaps driven by AT-family kinases and DNA-PK.

In vivo

Administered 30 minutes after gemcitabine, 4 mg/kg SCH 900776 is sufficient to induce the γ-H2AX biomarker while 8 mg/kg leads to enhanced tumor pharmacodynamic and regression responses relative to gemcitabine or SCH 900776 alone. Dose escalation of SCH 900776 (16 mg/kg and 32 mg/kg) induces incremental improvements in tumor response. Importantly, doses of SCH 900776 associate with robust biomarker activation and improved tumor response are not associated with enhanced toxicity of gemcitabine on hematological parameters in BALB/c mice.
Cell Data

cell lines：

Concentrations：

Incubation Time：

Powder Purity:≥96%

Specifications

Sinónimos

6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-((R)-piperidin-3-yl)pyrazolo[1, 5-a]pyrimidin-7-amine

Especificaciones y pureza

2mM in DMSO

Mecanismos bioquímicos y fisiológicos

MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Tipo de acción

INHIBITOR

Mecanismo de acción

Serine/threonine-protein kinase Chk1 inhibitor

Propiedades del producto

• ALogP: 0.8

Nombres e identificadores

• Isómeros SMILES: CN1C=C(C=N1)C2=C3N=C(C(=C(N3N=C2)N)Br)[C@@H]4CCCNC4
• PubChem CID: 46239015
• Peso molecular: 376.25

Objetivos asociados (humanos)

PSMC4 Tchem 26S proteasome regulatory subunit 6B (1 Activities)

Discover Target: PSMC4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CHEK1 Tchem Serine/threonine-protein kinase Chk1 (2 Activities)

Discover Target: CHEK1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Propiedades químicas y físicas

• Solubilidad: Solubility (25°C) In vitro DMSO: 48 mg/mL (197.35 mM); Water: 48 mg/mL (197.35 mM); Ethanol: Insoluble