GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

Acetamide, N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

Apremilast (CC-10004) is a potent and orally activePDE4andTNF-αinhibitor withIC50of 74 nM and 77 nM, respectively.
In vitro

Apremilast is more potent for inhibition of PDE4 compared with cAMP or cGMP hydrolysing enzymes from other PDE families. Apremilast displays a broad pattern of anti-inflammatory activity in a variety of cell types, inhibits TNF-α, IL-12 and IL-23 production, as well as NK and keratinocyte responses. Apremilast is found to inhibit the zymosan-induced PMN production of IL-8 with IC50 of 94 nM. Apremilast inhibits fMLF-induced PMN CD18 and CD11b expression with IC50 of 390 nM and 74 nM, respectively, and inhibits fMLF-induced adhesion of PMN to HUVECs with IC50 of 150 nM. Apremilast inhibits keratinocyte TNF-αproduction, with no effect on keratinocyte cell viability as measured by intracellular ATP levels. .

In vivo

Apremilast is stable in the presence of human microsomes (t1/2 > 60 min). It is 90% protein bound in human plasma. Oral and intravenous administration of it in female rats showed that it have good pharmacokinetics with low clearance, a moderate volume of distribution, and a 64% oral bioavailability. In a LPS-induced TNF-αinhibition model in rats, examined the TNF-α inhibitory ability of Apremilast in vivo, and the ED50 is determined to be 0.03 mg/kg. In another LPS-induced neutrophilia model in rats, Apremilast exhibited an ED50 range from 0.3 mg/kg to 0.9 mg/kg.
Cell Data

cell lines：59 cancer cell lines

Concentrations：~10 μM

Incubation Time：18 h

Powder Purity:≥99%

Specifications

Sinónimos

Acetamide, N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2, 3-dihydro-1, 3-dioxo-1H-isoindol-4-yl]-

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.

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

Mecanismo de acción

Phosphodiesterase 4 inhibitor

Propiedades del producto

• ALogP: 1.8

Nombres e identificadores

• Isómeros SMILES: CCOC1=C(C=CC(=C1)[C@@H](CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC
• CAS alternativo: 608141-41-9
• Términos de entrada MeSH: apremilast;CC 10004;CC-10004;CC10004;Otezla
• Peso molecular: 460.5
• Reaxy-Rn: 14176765
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=14176765&ln=

Objetivos asociados (humanos)

PDE4D Tclin cAMP-specific 3',5'-cyclic phosphodiesterase 4D (6 Activities)

Discover Target: PDE4D

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

PDE4C Tclin cAMP-specific 3',5'-cyclic phosphodiesterase 4C (1 Activities)

Discover Target: PDE4C

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

PDE4A Tclin cAMP-specific 3',5'-cyclic phosphodiesterase 4A (1 Activities)

Discover Target: PDE4A

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

PDE4B Tclin cAMP-specific 3',5'-cyclic phosphodiesterase 4B (4 Activities)

Discover Target: PDE4B

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: 64 mg/mL (199.75 mM); Ethanol: 64 mg/mL (199.75 mM); Water: Insoluble

Referencias

1. Zhendong Song, Yi-You Huang, Ke-Qiang Hou, Lu Liu, Feng Zhou, Yue Huang, Guohui Wan, Hai-Bin Luo, Xiao-Feng Xiong.  (2022)  Discovery and Structural Optimization of Toddacoumalone Derivatives as Novel PDE4 Inhibitors for the Topical Treatment of Psoriasis.  JOURNAL OF MEDICINAL CHEMISTRY,      [PMID:35188767] [10.1021/acs.jmedchem.1c02058]

2. Yun Huang, Chu-Ru Mao, Yijie Lou, Shuai Zhan, Zhe Chen, Wanjing Ding, Zhongjun Ma.  (2023)  Design, Synthesis, and Biological Evaluation of an Orally Bioavailable, Potent, and Selective ROCK2 Inhibitor for Psoriasis Treatment.  JOURNAL OF MEDICINAL CHEMISTRY,      [PMID:37943013] [10.1021/acs.jmedchem.3c01297]