Atrasentan HCl

Alias: ABT 627; Abbott 147627; (+)A 127722; A147627; A 127722; ABT627; ABT-627; NSC720763; US trade name: Xinlay

Cat No.:V4422 Purity: ≥98%

COA Product Data Instructions for use SDS

Atrasentan HCl Chemical Structure CAS No.: 195733-43-8
Product category: Endothelin Receptor

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Atrasentan HCl:

Atrasentan

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information

Product Description

Atrasentan HCl, the hydrochloride salt of Atrasentan (NSC-720763; ABT-627; A-147627; trade name: Xinlay), is a novel and selective endothelin receptor antagonist (IC50 = 0.0551 nM for ETA) with anticancer activity. Atrasentan may be used to treat metastatic hormone-refractory prostate cancer since it is made to inhibit the effects of endothelin-1.

Biological Activity I Assay Protocols (From Reference)

Targets

ETA ( IC50 = 0.055 nM )

ln Vitro

Atrasentan (ABT-627, 0-50 μM) strongly inhibits the growth of LNCaP and C4-2b prostate cancer cells. When combined with Taxotere, ABT-627 causes a notably higher reduction in viable prostate cancer cells compared to when either drug is used alone. It also exhibits a higher degree of NF-κB DNA binding activity down-regulation[2]. Atrasentan significantly induces a number of CYPs and drug transporters (CYP3A4 is 12-fold induced at 50 μM, for example). It is a weak BCRP inhibitor (IC50 in MDCKII-BCRP cells = 59.8±11 μM) and a moderate P-gp inhibitor (IC50 in P388/dx cells = 15.1±1.6 μM)[3].

ln Vivo

Atrasentan (3 mg/kg, p.o.) suppresses the pressor response brought on by big endothelin-1 (1 nmol/kg) in pithed rats[1]. Aatrasentan (ABT-627, 10 mg/kg, i.p.) and Taxotere alone partially inhibited the growth of C4-2b tumors within the bone environment in the SCID-hu model[2].

Cell Assay

In 96-well microtiter culture plates, three times as many cells (LNCaP, C4-2b, and PC-3) are seeded per well, or a density of 3 × 10³ cells. Following an overnight incubation period, the medium is extracted and substituted with a new medium that comprises varying concentrations of ABT-627 (0-50 μM) diluted from a 10-mM stock. Each well receives 20 μL of MTT solution (5 mg/mL in PBS) after the drug has been incubated for 72 hours.The wells are then left to incubate for an additional two hours. The process ends with the aspiration of the supernatant and the dissolution of the MTT formazan (produced by metabolically viable cells) in 100 μL of isopropanol. A plate reader is used to measure the absorbance at 595 nm after the plates are mixed for 30 minutes on a gyratory shaker.

Animal Protocol

Rats are orally given YM598 (0.3, 1, and 3 mg/kg), atrasentan (0.3, 1, and 3 mg/kg), or 0.5% methyl cellulose as a vehicle using a dosing cannula. 5 mL/kg is the dosage volume for both the test material and the vehicle. The rats are anesthetized with NSC 10816 about 20 minutes after the compounds are administered, and 30 minutes after dosing, they are pithed and ventilated. Big endothelin-1 (1 nmol/kg) is injected intravenously and blood pressure is recorded about an hour after the compounds are taken orally. In these two experiments, linear regression analysis is used to determine the dose of test compound that causes 50% inhibition (ID50) of the big endothelin-1-induced increase in diastolic blood pressure.

References

[1]. Superiority of YM598 over atrasentan as a selective endothelin ETA receptor antagonist. Eur J Pharmacol. 2004 Sep 13;498(1-3):171-7.

[2]. In vitro and in vivo molecular evidence for better therapeutic efficacy of ABT-627 combination in prostate cancer. Cancer Res. 2007 Apr 15;67(8):3818-26.

[3]. Interaction potential of the endothelin-A receptor antagonist atrasentan with drug transporters and drug-metabolising enzymes assessed in vitro. Cancer Chemother Pharmacol. 2011 Oct;68(4):1093-8.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C29H39CLN2O6
Molecular Weight	547.08276
Exact Mass	546.25
Elemental Analysis	C, 63.67; H, 7.19; Cl, 6.48; N, 5.12; O, 17.55
CAS #	195733-43-8
Related CAS #	Atrasentan; 173937-91-2
Appearance	Solid powder
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.Cl
InChi Key	IJFUJIFSUKPWCZ-SQMFDTLJSA-N
InChi Code	InChI=1S/C29H38N2O6.ClH/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);1H/t23-,27-,28+;/m1./s1
Chemical Name	(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid;hydrochloride
Synonyms	ABT 627; Abbott 147627; (+)A 127722; A147627; A 127722; ABT627; ABT-627; NSC720763; US trade name: Xinlay
HS Tariff Code	2934.99.9001
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)

Solubility Data

Solubility (In Vitro)	DMSO: ~28.57 mg/mL (~52.2 mM) H2O: ~0.5 mg/mL (~0.9 mM) 0.1 M HCL: < 1 mg/mL

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8279 mL	9.1394 mL	18.2789 mL
	5 mM	0.3656 mL	1.8279 mL	3.6558 mL
	10 mM	0.1828 mL	0.9139 mL	1.8279 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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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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.

Note： (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.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00046943	Completed	Drug: atrasentan hydrochloride	Prostate Cancer	Abbott	September 2002	Phase 3
NCT00039429	Completed	Drug: atrasentan hydrochloride	Kidney Cancer	Eastern Cooperative Oncology Group	July 14, 2003	Phase 2
NCT00134056	Completed	Drug: atrasentan hydrochloride Drug: docetaxel	Metastatic Cancer Prostate Cancer	SWOG Cancer Research Network	August 2006	Phase 3
NCT02118714	Completed	Drug: Atrasentan	Nephropathy Diabetes	AbbVie	April 6, 2015	Phase 2
NCT00181558	Completed	Drug: Atrasentan Drug: Zoledronic Acid (Zometa)	Adenocarcinoma of the Prostate Prostate Cancer	Massachusetts General Hospital	December 2001	Phase 2