Dasatinib

SKU: orb1308592

Description

Dasatinib is an orally bioavailable, ATP-competitive tyrosine kinase inhibitor targeting Src and Bcr-Abl with high potency (Ki=16/30 pM). It is widely used in leukemia and lymphoma research, demonstrating antitumor efficacy in both in vitro cellular assays and in vivo animal models of cancer.

Research Area

Cell Biology, Immunology & Inflammation

Key Properties

• CAS Number: 302962-49-8
• MW: 488.0
• Purity: >98%
• Formula: C₂₂H₂₆ClN₇O₂S
• SMILES: CC1=NC(=CC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=N1)N1CCN(CCO)CC1
• Target: Kinase
• Solubility: Soluble in DMSO (up to 200 mg/ml).

Bioactivity

• Target IC50:
  Abl:0.6 nM (cell free)|lck:0.4 nM|FGFR1:880 nM|c-Kit (D816V):37 nM (cell free)|Her2:710 nM|MEK:1700 nM|yes:0.5 nM|PDGFRβ:28 nM|Src:0.8 nM (cell free)|c-Kit (WT):79 nM (cell free)|p38:100 nM|Her1:180 nM|p210 (BCR-ABL):1.0 nM
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• In Vivo:
  METHODS: To test the antitumor activity in vivo, Dasatinib (50 mg/kg in 80 mmol/L sodium citrate buffer, pH 3.0) was administered orally to athymic nude mice harboring human thyroid carcinoma tumors of BCPAP or 8505C, five days per week for 20 days. RESULTS: Dasatinib significantly inhibited BCPAP tumors in situ, with final tumor volume suppressed by more than 90%. Dasatinib treatment did not significantly inhibit the growth of 8505C-derived tumors at any time point. METHODS: To investigate the effects on neuroinflammation, Dasatinib (20 mg/kg in 4%DMSO+30%PEG+5%Tween 80) was administered intraperitoneally or orally to C57BL6/N mice once daily for four days, followed by intraperitoneal injection of LPS (10 mg/kg) to induce neuroinflammatory responses in vivo. RESULTS: Intraperitoneal injection and oral administration of Dasatinib inhibited LPS-induced activation of microglia/astrocytes, pro-inflammatory cytokine levels, and neutrophil rolling in the brains of wild-type mice.
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• In Vitro:
  METHODS: Eight thyroid cancer cells were treated with Dasatinib (0.019-1.25 μmol/L) for 3 days, and cell proliferation was detected by SRB. RESULTS: The IC50 of Dasatinib on C643, TPC1, BCPAP, SW1736, K1, 8505C, HTh74 and HTh7 cells were 0.09, 0.03, 0.04, 0.08, 0.4, 2.7, >5 and 1.6 μmol/L, respectively. METHODS: Human lung cancer cells NCI-H1975 and NCI-H1650 were treated with Dasatinib (2.5-20 μM) for 48 h. Apoptosis was detected by Flow Cytometry. RESULTS: Dasatinib induced apoptosis in NCI-H1975 and NCI-H1650 cells at 10 and 20 μM.
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• Cell Research:
  Ba/F3 cell lines were plated in triplicate and incubated with escalating concentrations of imatinib, AMN107, or BMS-354825 for 72 hours. Proliferation was measured using a methanethiosulfonate-based viability assay. IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 and IC90 determinations were 0 to 2,000 nmol/L (imatinib and AMN107) or 0 to 32 nmol/L (BMS-354825). The imatinib concentration range was extended to 6,400 nmol/L for mutants with IC50 >2,000 nmol/L. The BMS-354825 concentration range was extended to 200 nmol/L for mutant T315I .
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• Animal Research:
  For in vivo studies, dasatinib (50 mg/kg) was prepared for daily oral gavage (5 d/wk) in 80 mmol/L sodium citrate buffer, pH 3.0. For the orthotopic murine model, mice were randomized on day 10 based on bioluminescence activity to receive drug or vehicle. In the metastatic murine model, mice received dasatinib or vehicle, as described earlier, starting 2 days before intracardiac injection (pretreatment), or on day 11 following randomization (posttreatment) .
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BMS-354825

Compound Identifiers

PubChem CID

3062316