| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Atrasentan sodium selectively targets and inhibits the endothelin A receptor. It exhibits a Ki of 0.034 nM and an IC₅₀ of 0.055 nM for the ETA receptor. Atrasentan demonstrates >1800-fold selectivity for ETA over the ETB receptor (Ki of 63.3 nM for ETB). The ETA receptor is the primary effector receptor for endothelin-1, mediating vasoconstriction, inflammation, and fibrosis in tissues including the kidney and vasculature.
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|---|---|
| ln Vitro |
In vitro studies demonstrate that atrasentan inhibits [¹²⁵I]ET-1 binding to CHO cells overexpressing the human ETA receptor with a pKi of 10.47 (Ki 0.03 nM). In LNCaP and C4-2b prostate cancer cells, atrasentan (0-50 μM) significantly inhibits cell proliferation, with enhanced effects on viable cell reduction when combined with Taxotere. Atrasentan significantly induces the expression of multiple CYP enzymes and drug transporters (e.g., 12-fold induction of CYP3A4 at 50 μM), with IC₅₀ values of 59.8±11 μM for BCRP and 15.1±1.6 μM for P-gp.
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| ln Vivo |
In the SONAR trial (NCT01858532) of patients with type 2 diabetic nephropathy, atrasentan (0.75 mg once daily) reduced the risk of the primary composite renal endpoint by 29% (HR=0.65, 95% CI: 0.49-0.88) and decreased proteinuria by 36%. In the ALIGN trial (NCT04573478), after 36 weeks of atrasentan treatment, UPCR in IgAN patients decreased by 38.1% from baseline, compared to a 3.1% decrease in the placebo group, with a between-group difference of 36.1% (95% CI: 44.6%~26.4%, P<0.001). In hypophysectomized rats, oral atrasentan (3 mg/kg) inhibits the pressor response induced by big endothelin-1 (1 nmol/kg).
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| Enzyme Assay |
Radioligand binding assays are used to evaluate the binding affinity of atrasentan to the ETA receptor. Membrane preparations from CHO cells expressing the human ETA receptor are incubated with [¹²⁵I]ET-1 and varying concentrations of atrasentan. Bound and free radioligands are separated by filtration, and radioactivity is measured to calculate Ki and IC₅₀ values.
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| Cell Assay |
Cell Proliferation Assay: LNCaP, C4-2b, and PC-3 prostate cancer cells are seeded in 96-well plates at a density of 3 × 10³ cells per well. After overnight culture, the medium is replaced with fresh medium containing various concentrations of atrasentan (0-50 μM). After 72 hours of drug treatment, 20 μL of MTT solution (5 mg/mL) is added to each well and incubated for an additional 2 hours. The supernatant is then removed, and 100 μL of isopropanol is added to dissolve the formazan crystals. After mixing on a shaker for 30 minutes, absorbance is measured at 595 nm.
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| Animal Protocol |
Hypophysectomized Rat Model: Rats receive oral atrasentan (0.3, 1, 3 mg/kg) or vehicle (0.5% methylcellulose) at a dosing volume of 5 mL/kg. Approximately 20 minutes after administration, rats are anesthetized with sodium pentobarbital, hypophysectomized, and artificially ventilated. Approximately 1 hour after administration, big endothelin-1 (1 nmol/kg) is injected intravenously, and blood pressure changes are recorded. Linear regression analysis is used to calculate the dose required to inhibit big endothelin-1-induced diastolic blood pressure elevation by 50% (ID₅₀).
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| ADME/Pharmacokinetics |
Atrasentan is well absorbed orally, with AUC increasing proportionally to dose over the 0.35-30 mg dose range. Steady state is achieved after 7 days of continuous dosing, with an AUC accumulation ratio of approximately 2-3 fold compared to the initial dose. A high-fat diet has no significant effect on its pharmacokinetics.
Plasma protein binding: >99%
Elimination half-life: 24-41 hours
Apparent clearance: 19 L/h
Metabolism: Approximately 50% via CYP3A, with the remainder via glucuronidation by multiple UGTs
Excretion: Following a single 10 mg oral dose, approximately 86% is excreted in feces, with <4% excreted in urine
Special populations: Gender, age, race, mild-to-severe renal impairment, and mild-to-moderate hepatic impairment have no significant effect on pharmacokinetics; use in severe hepatic impairment or end-stage renal disease is not recommended
Genetic Polymorphism Impact: The OATP1B1 transporter, encoded by the SLCO1B1 gene, shows the strongest correlation with atrasentan plasma exposure, classifying patients as OATP1B1 normal or slow phenotypes.
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| Toxicity/Toxicokinetics |
BOXED WARNING: EMBRYO-FETAL TOXICITY
Atrasentan may cause serious birth defects and is contraindicated in pregnancy.
Common Adverse Reactions (incidence ≥5%):
Peripheral edema (10%)
Anemia (6%)
Other Adverse Reactions (≥2% and higher than placebo):
Elevated liver transaminases (2%)
Warnings and Precautions:
Hepatotoxicity: May cause elevated aminotransferases, hepatotoxicity, and liver failure. Liver function should be assessed before treatment, and therapy should be discontinued if symptoms of liver injury occur
Fluid retention: May cause peripheral edema, primarily related to hemodilution
Decreased sperm count: May affect male fertility
Drug interactions: Avoid concomitant use with strong or moderate CYP3A inducers and OATP1B1/1B3 inhibitors
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| References |
|
| Molecular Formula |
C29H37N2NAO6
|
|---|---|
| Molecular Weight |
532.60
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| Exact Mass |
532.254931
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| Elemental Analysis |
C, 65.40; H, 7.00; N, 5.26; Na, 4.32; O, 18.02
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| CAS # |
178738-96-0
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| Related CAS # |
173937-91-2 (free acid); 195733-43-8 (HCl); 195704-72-4 (free acid)； 178738-96-0 (sodium)
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| PubChem CID |
23673480
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
38
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| Complexity |
741
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
CCCCN(CCCC)C(=O)CN1C[C@@H]([C@H]([C@@H]1C2=CC=C(C=C2)OC)C(=O)[O-])C3=CC4=C(C=C3)OCO4.[Na+]
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| InChi Key |
JQWVNUYJUQFYPN-SQMFDTLJSA-M
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| InChi Code |
InChI=1S/C29H38N2O6.Na/c1-4-6-14-30(15-7-5-2)26(32)18-31-17-23(21-10-13-24-25(16-21)37-19-36-24)27(29(33)34)28(31)20-8-11-22(35-3)12-9-20;/h8-13,16,23,27-28H,4-7,14-15,17-19H2,1-3H3,(H,33,34);/q;+1/p-1/t23-,27-,28+;/m1./s1
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| Chemical Name |
sodium (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate
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| Synonyms |
178738-96-0; Atrasentan sodium; A147627; (+) A 127722; A 127722; ABT627; ABT 627; ABT-627; NSC720763; Abbott 147627; US brand name: Xinlay; Atrasentan (sodium); orb1739282;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8776 mL | 9.3879 mL | 18.7758 mL | |
| 5 mM | 0.3755 mL | 1.8776 mL | 3.7552 mL | |
| 10 mM | 0.1878 mL | 0.9388 mL | 1.8776 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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