5.00653

Nef Hck Activation Inhibitor, B9

• Sinónimos: Nef Hck Activation Inhibitor, B9, Nef Dimerization Blocker, ( E)-4-((3-Chlorophenyl)diazenyl)-5-hydroxy-3-(4-nitrophenyl)-1H-pyrazole-1-carbothioamide, Nef Dimerization Blocker, (E)-4-((3-Chlorophenyl)diazenyl)-5-hydroxy-3-(4-nitrophenyl)-1H-pyrazole-1-carbothioamide
• Fórmula empírica (notación de Hill): C₁₆H₁₁ClN₆O₃S
• Número de CAS: 1596216-24-8
• Peso molecular: 402.81
• Código UNSPSC: 51111800
• ID de la sustancia en PubChem: 4553981
• NACRES: NA.77

Propiedades

• Ensayo: ≥98% (HPLC)
• Nivel de calidad: 100
• Formulario: powder
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: orange
• solubilidad: DMSO: 2.5 mg/mL
• temp. de almacenamiento: 2-8°C
• cadena SMILES: C1=CC(=CC(=C1)Cl)N=NC2=C(NN(C2=O)C(=S)N)C3=CC=C(C=C3)[N+](=O)[O-]
• InChI: 1S/C16H11ClN6O3S/c17-10-2-1-3-11(8-10)19-20-14-13(21-22(15(14)24)16(18)27)9-4-6-12(7-5-9)23(25)26/h1-8,21H,(H2,18,27)
• Clave InChI: LEQSBTDRMOZWRP-UHFFFAOYSA-N

Descripción

Descripción general

A cell-permeable diphenylpyrazolo compound that is shown to disrupt HIV accessary protein Nef dimerization (IC₅₀ = 3 µM in HEK293T cells) and prevent Nef-mediated Src family kinase (SFK) Hck activation (IC₅₀ = 2.8 µM) without directly affecting the catalytic activity of c-Src, Hck, Lck, or Lyn (IC₅₀ >20 µM). Shown to effectively suppress HIV and SIV viral replication (IC₅₀<0.3 µM in 9 d HIV-1 NL4-3-infected CEM-T4 cultures; IC₅₀ = 1 µM in 5 d SIV ΔB670-infected CEM-174 cultures) and infectivity (45% and 50% inhibition against HIV-1 NL4-3 and SIV ΔB670, respectively, following 48 h 3 µM B9 treatment in TZM-bl reporter cells) in a Nef-dependent manner, being ineffective against the replication of Nef-defective HIV-1 mutant. Molecular docking studies predict a high-affinity B9-targeting site formed at the Nef dimerization interface and a low-affinity B9-binding site on each Nef monomer at the dimer interface periphery, with Asn126 contributing to both modes of binding. Consistently, in vitro binding studies reveal two B9 K_D values of 1.72 nM and 860 nM toward full-length HIV-1 Nef and a complete loss of B9 binding toward Nef N126A/L/Q mutants.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
Nef

Reversible: yes

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Otras notas

Emert-Sedlak, L.A., et al. 2013. Chem. Biol.20, 82.

Información legal

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 2
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable