MI-503 - Moligand™, 10mM in DMSO , CAS No.1857417-13-0

CAS: 1857417-13-0 Cat. No.: M408598 Fórmula: C₂₈H₂₇F₃N₈S Peso molecular: 564.63

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

1H-​Indole-​2-​carbonitrile, 4-​methyl-​1-​(1H-​pyrazol-​4-​ylmethyl)​-​5-​[[4-​[[6-​(2,​2,​2-​trifluoroethyl)​thieno[2,​3-​d]​pyrimidin-​4-​yl]​amino]​-​1-​piperidinyl]​methyl]​-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

MI-503 MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM. It shows pronounced growth suppressive activity in a panel of human MLL leukemia cell lines(GI50 at 250 nM-570 nM range), but only a minimal effect in human leukemia cell
In vitro

Treatment of murine bone marrow cells (BMC) transformed with the MLL-AF9 oncogene with MI-503 results in substantial growth inhibition, with half-maximal growth inhibitory concentration (GI50) values of 0.22 μM, measured after 7 days of treatment. The cell growth inhibitory effect of MI-503 is time-dependent, with a pronounced effect achieved after 7-10 days of treatment. MI-503 is also very effective in inducing differentiation of MLL leukemia cells and substantially increases expression of CD11b, a myeloid differentiation marker. These effects are accompanied by reduced c-kit (CD117) expression, a marker associated with leukemia stem cells (LSCs). Treatment with sub-micromolar concentrations of MI-503 also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias.

In vivo

MI-503 has very favorable drug-like properties, including metabolic stability and pharmacokinetic profile in mice. It blocks hematologic tumors in vivo and reduces MLL leukemia tumor burden. MI-503 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (~75%). Prolonged treatment (38 days) with MI-503 induces no toxicity in mice as reflected by no alterations in the body weight and no morphological changes in liver and kidney tissues. MI-503 could substantially improve survival of MLL leukemic mice and does not impair normal hematopoiesis in vivo.
Cell Data

cell lines：

Concentrations：--

Incubation Time：7days

Powder Purity:≥99%

Specifications

Sinónimos

1H-​Indole-​2-​carbonitrile, 4-​methyl-​1-​(1H-​pyrazol-​4-​ylmethyl)​-​5-​[[4-​[[6-​(2,​2,​2-​trifluoroethyl)​thieno[2,​3-​d]​pyrimidin-​4-​yl]​amino]​-​1-​piperidinyl]​methyl]​-

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM. It shows pronounced growth suppressive activity in a panel of human MLL leukemia cell lines(GI50 at 250 nM-570 nM range), but only a minimal effect in human leukemia cell lines wit

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.

Grado

Moligand™

Tipo de acción

INHIBITOR

Nombres e identificadores

• Isómeros SMILES: CC1=C(C=CC2=C1C=C(N2CC3=CNN=C3)C#N)CN4CCC(CC4)NC5=C6C=C(SC6=NC=N5)CC(F)(F)F
• Peso molecular: 564.63
• Reaxy-Rn: 29186448
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=29186448&ln=

Objetivos asociados (humanos)

MEN1 Tchem Menin (3 Activities)

Discover Target: MEN1

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