SML2098

KINK-1 hydrochloride

≥98% (HPLC)

• Synonym(e): 7-[2-(Cyclopropylmethoxy)-6-hydroxyphenyl]-1,4-dihydro-5-(3S)-3-piperidinyl-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride, 7-[2-(Cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-3-piperidinyl]-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride, Bay 65-1942, CmpdA, Compound A, Kinase Inhibitor of NF-ΚB-1
• Empirische Formel (Hill-System): C₂₂H₂₅N₃O₄ · HCl
• CAS-Nummer: 600734-06-3
• Molekulargewicht: 431.91
• MDL-Nummer: MFCD11040976
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥98% (HPLC)
• Form: powder
• Optische Aktivität: [α]/D -19 to -24°, c = 0.2 in DMF
• Lagerbedingungen: desiccated
• Farbe: white to beige
• Löslichkeit: DMSO: 2 mg/mL, clear
• Lagertemp.: −20°C
• SMILES String: OC1=CC=CC(OCC2CC2)=C1C3=NC(NC(OC4)=O)=C4C([C@@H]5CCCNC5)=C3.Cl
• InChI: 1S/C22H25N3O4.ClH/c26-18-4-1-5-19(28-11-13-6-7-13)20(18)17-9-15(14-3-2-8-23-10-14)16-12-29-22(27)25-21(16)24-17;/h1,4-5,9,13-14,23,26H,2-3,6-8,10-12H2,(H,24,25,27);1H/t14-;/m1./s1
• InChIKey: XZTOAEZYOFWVHB-PFEQFJNWSA-N

Beschreibung

Biochem./physiol. Wirkung

KINK-1 (Kinase Inhibitor of NF-ΚB-1; Bay 65-1942; CmpdA; Compound A) is an ATP-competitive, IKKβ-selective IΚB kinase (IKK) inhibitor (Ki against ATP = 2 nM/IKKβ and 135 nM/IKKα) that potently inhibits IKKβ-catalyzed GST-IΚBα(1–54) phosphorylation (IC50 = 4 nM, 200 nM ATP) without affecting (IC50 >10μM) IKK3 or 27 other kinases, lipases, phosphatases, caspases, and MMPs. KINK-1 effectively inhibits NF-ΚB activation and cytokines production in various human and murine cultures (IC50 from 18 to 502 nM) and is efficacious against LPS-induced plasma TNF-α production in mice and rats in vivo (EC50 = 9.1 and 6.6 mg/kg p.o., repectively) with good pharmacokinetic profile and oral availability. KINK-1 is also shown to effectively inhibit OVA-induced lung inflammation in a rat model of asthma (ED50 <0.3 mg/kg p.o.) without adverse effects to the animals.

Orally active, potent, ATP-competitive, IKKβ (IKK2)-selective inhibitor with anti-inflammatory and anti-cancer efficacy in vivo.

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable