SML4475

Ponatinib hydrochloride

≥98% (HPLC)

• Synonym(e): 3-(Imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide Hydrochloride, AP24534 HCl, Ponatinib HCl
• Empirische Formel (Hill-System): C₂₉H₂₇F₃N₆O · xHCl
• Molekulargewicht: 532.56 (free base basis)
• UNSPSC Code: 12352200
• Assay: ≥98% (HPLC)
• Form: powder
• Storage condition: desiccated

Eigenschaften

• Quality Segment: 100
• assay: ≥98% (HPLC)
• form: powder
• storage condition: desiccated
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear (warmed)
• storage temp.: -10 to -25°C

Beschreibung

Biochem/physiol Actions

AP24534 (Ponatinib) is a reversible, ATP-competitive, BBB-permeable and orally active pan-BCR-ABL inhibitor engineered to overcome multidrug-resistant CML. Its design features a rigid ethynyl linker that bypasses the steric hindrance of the T315I "gatekeeper" mutation, yielding profound potency against native ABL (IC50 0.37 nM), T315I (IC50 2.0 nM), and T315I-inclusive compound mutants (IC50 0.30–0.44 nM). This efficacy extends to cellular models, where it suppresses CrkL phosphorylation and inhibits proliferation in native (IC50 0.5 nM) and T315I-expressing (IC50 11 nM) cells. Beyond ABL, Ponatinib acts as a multi-kinase inhibitor modulating angiogenesis and stromal signaling, with high affinity for LYN (0.24 nM), PDGFRα (1.1 nM), VEGFR2 (1.5 nM), FGFR1-4 (~2.2 nM), SRC (5.4 nM), KIT (~12.5 nM), and FLT3 (~13 nM). Mechanistically, it halts STAT5, ERK, and AKT signaling to trigger cell cycle arrest and intrinsic apoptosis—driven by caspase-3 cleavage and Bcl-xL/Mcl-1 downregulation—or RIPK1/3-mediated necroptosis. To deepen molecular response against complex resistance, Ponatinib demonstrates significant synergy with MDM2 inhibitors, the allosteric inhibitor asciminib, and the BCL-2 inhibitor venetoclax.

Disclaimer

Hygroscopic, Store with desiccant

Sicherheitshinweise

• Hazard Classifications: Acute Tox. 3 Oral - Repr. 2 - STOT RE 1 Dermal
• Zielorgane: Liver,Bone marrow,Pancreas,Cardio-vascular system
• Lagerklasse: 6.1C - Combustible acute toxic Cat.3 / toxic compounds or compounds which causing chronic effects
• Piktogramme: GHS06,GHS08
• Signalwort: Danger
• Gefahrencodes: H301,H361fd,H372
• Sicherheitshinweise: P202 - P260 - P264 - P280 - P301 + P310 + P330 - P308 + P313