{{Short description|Chemical compound}} {{Use dmy dates|date=April 2025}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 458631282 | image = Atrasentan structure.svg | image_class = skin-invert-image | width = | alt = | caption = | USAN = atrasentan hydrochloride
<!-- Clinical data --> | pronounce = | tradename = Vanrafia | Drugs.com = {{drugs.com|monograph|atrasentan}} | MedlinePlus = a625070 | DailyMedID = Atrasentan | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU_comment = | pregnancy_category = Contraindicated | routes_of_administration = By mouth | class = Endothelin receptor antagonist | ATC_prefix = None | ATC_suffix = | ATC_supplemental = | biosimilars =
<!-- Legal status --> | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> | legal_AU_comment = | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 --> | legal_BR_comment = | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Vanrafia FDA label">{{cite web | title=Vanrafia- atrasentan tablet, film coated | website=DailyMed | date=2 April 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9a7e7f85-bfd0-44a0-beda-3bcfa8215c64 | access-date=17 April 2025}}</ref> | legal_EU = | legal_EU_comment = | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above -->
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | index2_label = as HCl | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 173937-91-2 | CAS_number2 = 195733-43-8 | PubChem = 159594 | PubChem2 = 159595 | IUPHAR_ligand = | DrugBank = DB06199 | DrugBank2 = DBSALT001999 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 140321 | ChemSpiderID2 = 140322 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = V6D7VK2215 | UNII2 = E4G31X93ZA | KEGG = | KEGG2 = D03009 | ChEBI = 135810 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 9194 | ChEMBL2 = 2106068 | NIAID_ChemDB = | PDB_ligand = | synonyms = ABT-627, A-127722
<!-- Chemical and physical data --> | IUPAC_name = (2''R'',3''R'',4''S'')-4-(1,3-Benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid | C=29 | H=38 | N=2 | O=6 | 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 | SMILES2 = Cl.CCCCN(CCCC)C(=O)CN1C[C@@H]([C@H]([C@@H]1C1=CC=C(OC)C=C1)C(O)=O)C1=CC=C2OCOC2=C1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C29H38N2O6/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)/t23-,27-,28+/m1/s1 | StdInChI2 = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = MOTJMGVDPWRKOC-QPVYNBJUSA-N | StdInChIKey2 = IJFUJIFSUKPWCZ-SQMFDTLJSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}
'''Atrasentan''', sold under the brand name '''Vanrafia''', is a medication used to reduce proteinuria.<ref name="Vanrafia FDA label" /> It is an endothelin receptor antagonist.<ref name="Vanrafia FDA label" /> It is taken by mouth.<ref name="Vanrafia FDA label" />
Atrasentan was approved for medical use in the United States for IgA nephropathy in April 2025.<ref name="Vanrafia FDA label" /><ref name="Novartis PR 20250403">{{cite press release | title=Novartis receives FDA accelerated approval for Vanrafia (atrasentan), the first and only selective endothelin A receptor antagonist for proteinuria reduction in primary IgA nephropathy (IgAN) | website=Novartis | date=3 April 2025 | url=https://www.novartis.com/news/media-releases/novartis-receives-fda-accelerated-approval-vanrafia-atrasentan-first-and-only-selective-endothelin-receptor-antagonist-proteinuria-reduction-primary-iga-nephropathy-igan | access-date=4 April 2025}}</ref>
== Medical uses == Atrasentan is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy at risk of rapid disease progression, generally a urine protein-to-creatinine ratio >= 1.5 g/g.<ref name="Vanrafia FDA label" />
== Society and culture == === Legal status === Atrasentan was approved for medical use in the United States in April 2025.<ref name="Vanrafia FDA label" /><ref name="Novartis PR 20250403" />
=== Names === Atrasentan is the international nonproprietary name.<ref>{{cite journal | vauthors = ((World Health Organization)) | year = 2001 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 46 | journal = WHO Drug Information | volume = 15 | issue = 3–4 | hdl = 10665/71242 | hdl-access = free | author-link = World Health Organization | pages = 187–218 }}</ref>
Atrasentan is sold under the brand name Vanrafia.<ref name="Vanrafia FDA label" /><ref name="Novartis PR 20250403" />
== Research == === Clinical trials === Atrasentan failed a phase III trial for prostate cancer in patients unresponsive to hormone therapy.<ref>{{cite press release |title=Addition of experimental drug to standard chemotherapy for advanced prostate cancer shows no benefit in phase 3 clinical trial |publisher=National Cancer Institute |date=21 April 2011 |url=http://www.cancer.gov/newscenter/newsfromnci/2011/ProstateAtrasentanTrial |access-date=18 October 2014}}</ref> A second trial confirmed this finding.<ref>{{cite journal | vauthors = Quinn DI, Tangen CM, Hussain M, Lara PN, Goldkorn A, Moinpour CM, Garzotto MG, Mack PC, Carducci MA, Monk JP, Twardowski PW, Van Veldhuizen PJ, Agarwal N, Higano CS, Vogelzang NJ, Thompson IM | title = Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial | journal = The Lancet. Oncology | volume = 14 | issue = 9 | pages = 893–900 | date = August 2013 | pmid = 23871417 | pmc = 4277263 | doi = 10.1016/S1470-2045(13)70294-8 }}</ref>
A study published in 2014 showed that 0.75 mg and 1.25 mg of atrasentan reduced urinary albumin by 35 and 38% respectively with modest side effects. Patients also had decreased home blood pressures (but no change in office readings) decrease total cholesterol and LDL. Patients in the 1.25 mg dose group had increased weight gain which was presumably due to increased edema and had to withdraw from the study more than the placebo or 0.75 mg dose group.<ref>{{cite journal | vauthors = de Zeeuw D, Coll B, Andress D, Brennan JJ, Tang H, Houser M, Correa-Rotter R, Kohan D, Lambers Heerspink HJ, Makino H, Perkovic V, Pritchett Y, Remuzzi G, Tobe SW, Toto R, Viberti G, Parving HH | title = The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy | journal = Journal of the American Society of Nephrology | volume = 25 | issue = 5 | pages = 1083–93 | date = May 2014 | pmid = 24722445 | pmc = 4005314 | doi = 10.1681/ASN.2013080830 }}</ref>
In 2013, the SONAR trial<ref>{{ClinicalTrialsGov|NCT01858532|Study Of Diabetic Nephropathy With Atrasentan (SONAR)}}</ref> was initiated to determine if atrasentan reduces kidney failure in diabetic kidney disease.<ref name="HeerspinkParving2019">{{cite journal | vauthors = Heerspink HJ, Parving HH, Andress DL, Bakris G, Correa-Rotter R, Hou FF, Kitzman DW, Kohan D, Makino H, McMurray JJ, Melnick JZ, Miller MG, Pergola PE, Perkovic V, Tobe S, Yi T, Wigderson M, de Zeeuw D | title = Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial | journal = Lancet | volume = 393 | issue = 10184 | pages = 1937–1947 | date = May 2019 | pmid = 30995972 | doi = 10.1016/S0140-6736(19)30772-X | s2cid = 113407761 | url = https://pure.rug.nl/ws/files/93428784/1_s2.0_S014067361930772X_main.pdf }}</ref>
In 2024, the phase III ALIGN trial found atrasentan to be effective in reducing proteinuria in participants with IgA nephropathy.<ref>{{cite journal | vauthors = Heerspink HJ, Jardine M, Kohan DE, Lafayette RA, Levin A, Liew A, Zhang H, Lodha A, Gray T, Wang Y, Renfurm R, Barratt J | title = Atrasentan in Patients with IgA Nephropathy | journal = The New England Journal of Medicine | date = October 2024 | pmid = 39460694 | doi = 10.1056/NEJMoa2409415 | hdl = 11370/1e2616e6-a790-4100-a120-bcfeab18c3ce | hdl-access = free }}</ref><ref>{{cite press release | title=Novartis investigational atrasentan Phase III study demonstrates clinically meaningful and highly statistically significant proteinuria reduction in patients with IgA nephropathy (IgAN) | website=Novartis | date=30 October 2023 | url=https://www.novartis.com/news/media-releases/novartis-investigational-atrasentan-phase-iii-study-demonstrates-clinically-meaningful-and-highly-statistically-significant-proteinuria-reduction-patients-iga-nephropathy-igan | access-date=4 April 2025}}</ref>
Atrasentan is being studied for the treatment of various types of cancer,<ref>{{cite web | title=NCI Drug Dictionary | website=National Cancer Institute | date=2 February 2011 | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/atrasentan-hydrochloride | access-date=5 April 2025}}</ref> including non-small-cell lung cancer.<ref>{{cite journal | vauthors = Chiappori AA, Haura E, Rodriguez FA, Boulware D, Kapoor R, Neuger AM, Lush R, Padilla B, Burton M, Williams C, Simon G, Antonia S, Sullivan DM, Bepler G | title = Phase I/II study of atrasentan, an endothelin A receptor antagonist, in combination with paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer | journal = Clinical Cancer Research | volume = 14 | issue = 5 | pages = 1464–9 | date = March 2008 | pmid = 18316570 | doi = 10.1158/1078-0432.CCR-07-1508 | doi-access = }}</ref> It is also being investigated as a therapy for diabetic kidney disease.<ref>{{cite web | title = Atrasentan - Chinook Therapeutics | url = https://adisinsight.springer.com/drugs/800008541 | work = AdisInsight | publisher = Springer Nature Switzerland AG }}</ref>
== See also == Sparsentan
== References == {{Reflist}}
== External links == * {{ClinicalTrialsGov|NCT04573478|Atrasentan in Patients With IgA Nephropathy (ALIGN)}}
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Category:Carboxylic acids Category:Dibutylamino compounds Category:Endothelin receptor antagonists Category:Methylenedioxyphenethylamines Category:4-Methoxyphenyl compounds