Dapolsertib

SKU: orb2813910

Description

Dapolsertib (SEL24-B489) is an orally active, dual inhibitor of PIM kinases and FLT3-ITD. It reduces substrate phosphorylation and triggers apoptosis in leukemia cells in a dose-dependent manner. This compound is utilized in oncology research, showing activity in both cellular assays and in vivo models of hematological malignancies.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 1616359-00-2
• MW: 446.14
• Purity: 99.61% (May vary between batches)
• Formula: C₁₅H₁₈Br₂N₄O₂
• SMILES: O=N(=O)C=1C(Br)=C(Br)C=C2C1N=C(N2C(C)C)C3CCNCC3
• Target: FLT,Apoptosis,Pim
• Solubility: DMSO:15 mg/mL (33.62 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.48 mM)

Bioactivity

• Target IC50:
  Pim2:2 nM (Kd)|Pim1:2 nM (Kd)|Pim3:3 nM (Kd)
• In Vivo:
  Dapolsertib (25-100 mg/kg, orally) exhibited activity in AmL in vivo models . Dapolsertib induces apoptosis of DLBCL cell lines in low/sub-micromolar concentrations and exhibits activity in a xenograft model . Animal Model: SCID/beige mice bearing MV-4-11 tumors (FLT3-ITD+) . Dosage: 50, 75 and 100 mg/kg. Administration: Orally, twice daily. Result: Marked dose – dependent tumor reduction (67%, 74% and 82% tumor growth inhibition (TGI) for 50, 75 and 100 mg/kg daily doses, respectively).
• In Vitro:
  In MOLM-13 and to a lesser extent in MV4-11 cells, a dose-dependent disruption of cell cycle with especially pronounced depletion of the S phase after treatment with Dapolsertib, accompanied by PARP cleavage and apoptosis was observed . Dapolsertib causes a profound inhibition of S6 (S 235/236 ), but has little effect on PI3K/mTOR signaling . Dapolsertib inhibits STAT5 (Ser 726 ) and reduced expression of MCL1, whereas none of the selective inhibitors altered c-MYC abundance or induced PARP cleavage . Cell Viability Assay Cell Line: AZD1208, AC220 and AraC in AmL cell lines. Concentration: 0-10 μM. Incubation Time: 72 h. Result: Decreased viability.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SEL-24-B489, SEL24-B489, SEL24-B-489, SEL 24-B489, SEL24 B489, SEL24-B 489, SEL24B489, MEN1703, MEN 1703

Compound Identifiers

PubChem CID

76286825