Atrasentan hydrochloride

SKU: orb1296086

Description

Atrasentan hydrochloride

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 195733-43-8
• MW: 547.08
• Purity: 99.75%
• Formula: C₂₉H₃₉ClN₂O₆
• SMILES: Cl.CCCCN(CCCC)C(=O)CN1C[C@@H]([C@H]([C@@H]1c1ccc(OC)cc1)C(O)=O)c1ccc2OCOc2c1
• Target: Endothelin Receptor
• Solubility: DMSO:30 mg/mL (54.84 mM);H2O:0.4 mg/mL (0.73 mM);0.1 M HCL:< 1 mg/mL (insoluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.66 mM)

Bioactivity

• Target IC50:
  ETA:55.1 μM
• In Vivo:
  Atrasentan (3 mg/kg, p.o.) inhibits the pressor response induced by big endothelin-1 (1 nmol/kg) in pithed rats . Aatrasentan (10 mg/kg, i.p.) inhibited the C4-2b tumor growth within the bone environment to some extent in the SCID-hu model .
• In Vitro:
  Atrasentan (0-50 μM) significantly inhibits LNCaP and C4-2b prostate cancer cell growth. ABT-627 in combination with Taxotere elicits a significantly greater loss of viable prostate cancer cells relative to either agent alone and shows a greater degree of down-regulation of the NF-κB DNA binding activity . Atrasentan profoundly induces several CYPs and drug transporters. It is a moderate P-gp inhibitor (IC50: 15.1 μM in P388/dx cells) and a weak BCRP inhibitor (IC50: 59.8 μM in MDCKII-BCRP cells) .
• Cell Research:
  All three prostate cancer cell lines (LNCaP, C4-2b, and PC-3 cells) are seeded at a density of 3 × 10^3 cells per well in 96-well microtiter culture plates. After overnight incubation, the medium is removed and replaced with a fresh medium containing different concentrations of ABT-627 (0-50 μM) diluted from a 10-mM stock. After 72 h of incubation with the drug, 20 μL of MTT solution (5 mg/mL in PBS) is added to each well and incubated further for 2 h. Upon termination, the supernatant is aspirated and the MTT formazan formed by metabolically viable cells is dissolved in isopropanol (100 μL). The plates are mixed for 30 min on a gyratory shaker, and the absorbance is measured at 595 nm on a plate reader .
• Animal Research:
  YM598 (0.3, 1, and 3 mg/kg), atrasentan (0.3, 1, and 3 mg/kg), or 0.5% methylcellulose as vehicle is orally administered to rats with a dosing cannula. The dosing volume of the test substances and vehicle is set at 5 mL/kg. Approximately 20 min after administration of compounds, the rats are anesthetized with sodium pentobarbital, and then pithed and ventilated 30 min after dosing. Approximately 1 h after oral administration of compounds, big endothelin-1 (1 nmol/kg) is intravenously administered, and blood pressure is measured. In these two experiments, the dose of test compound that causes 50% inhibition (ID50) of the big endothelin-1-induced increase in diastolic blood pressure is determined by linear regression analysis .

Storage & Handling

• Storage: 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

Inhibitor, ET-A, EndothelinReceptor, Endothelin Receptor, inhibit, A 127722 Hydrochloride, A 147627, A 147627 Hydrochloride, A127722 Hydrochloride, A-127722 Hydrochloride, A147627, A-147627, A147627 Hydrochloride, A-147627 Hydrochloride, A-147627 hydrochloride, ABT 627, ABT 627 Hydrochloride, ABT627, ABT-627, ABT627 Hydrochloride, ABT-627 Hydrochloride, ABT-627 hydrochloride, (+)-A 127722, (+)-A 127722 hydrochloride, Atrasentan, Atrasentan hydrochloride, Atrasentan Hydrochloride

Compound Identifiers

PubChem CID

159595