SML3944

SJ11646

≥98% (HPLC)

• Synonym(e): N-(2-Chloro-6-methylphenyl)-2-((6-(4-(3-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetamido)propyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide, SJ 1011646, SJ 11646, SJ-1011646, SJ-11646, SJ1011646
• Empirische Formel (Hill-System): C₃₆H₄₀ClN₉O₅S
• CAS-Nummer: 2933135-82-9
• Molekulargewicht: 746.28
• UNSPSC Code: 12352200
• NACRES: NA.21
• Assay: ≥98% (HPLC)
• Form: powder

Eigenschaften

• Quality Segment: 100
• assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: -10 to -25°C
• SMILES string: CC1=NC(NC2=NC=C(C(NC3=C(C=CC=C3Cl)C)=O)S2)=CC(N4CCN(CC4)CCCNC(COC5=CC=C(C=C5)C6CCC(NC6=O)=O)=O)=N1
• InChI key: AJNQGWOQPRWRML-UHFFFAOYSA-N

Beschreibung

Biochem/physiol Actions

Potent ABL and SRC family tyrosine kinases (TYKs) degrader with greater antileukemic efficacy than dasatinib in cultures and in vivo.



SJ11646 is a potent and high-affinity (LCK/ABL1/SRC Kd = 0.14/0.054/0.17 nM for SJ11646 vs. 0.09/0.054/0.19 nM for dasatinib) ABL and SRC family tyrosine kinases (TYKs) degrader composed of dasatinib linked to a E3 ligase cereblon (CRBN)-binding ligand. SJ11646 effectively degrades SRC family TYKs in KOPT-K1 cells (LCK, CSK, SRC, FYN; 100 nM for 24h) and is 55,114-times more cytotoxic (LC50 = 0.0123 pM) than dasatinib against the BCR-ABL fusion-harboring B-ALL cell line SUP-B15. When used at equal molar amount via daily i.p., SJ11646 (15 mg/kg) shows significantly greater antileukemic efficacy than dasatinib (10 mg/kg) in two T-ALL PDX models in mice in vivo.

Sicherheitshinweise

• Lagerklasse: 11 - Combustible Solids
• Was ist los?: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable