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Chemical Structure| 2101700-15-4 Chemical Structure| 2101700-15-4

Structure of Pirtobrutinib
CAS No.: 2101700-15-4

Chemical Structure| 2101700-15-4

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Pirtobrutinib is a highly selective and non-covalent BTK inhibitor, which may be regarded as a third generation BTK inhibitor. It potently inhibited the cellular activity (measured by Y223 autophosphorylation) of BTK C481S, T and R mutations and displayed strong equilibrium binding to WT BTK and several BTK C481 substitution mutations. It may overcome acquired resistance to covalent BTK inhibitors in patients without significant off-target toxicity.

Synonyms: LOXO-305; LY 3527727; RXC-005

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Product Details of Pirtobrutinib

CAS No. :2101700-15-4
Formula : C22H21F4N5O3
M.W : 479.43
SMILES Code : C(N)(=O)C=1C(=NN([C@H](C(F)(F)F)C)C1N)C2=CC=C(CNC(=O)C3=C(OC)C=CC(F)=C3)C=C2
Synonyms :
LOXO-305; LY 3527727; RXC-005
MDL No. :N/A
InChI Key :FWZAWAUZXYCBKZ-NSHDSACASA-N
Pubchem ID :129269915

Safety of Pirtobrutinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Related Pathways of Pirtobrutinib

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
MEC-1 cells (overexpressing BTKC481R) 0.01, 0.1, 1 µM 1 hour Evaluate the inhibitory effect of Pirtobrutinib on the BCR signaling pathway; results showed that Pirtobrutinib inhibited phosphorylation of BTKC481R at 0.01 µM Blood Cancer J. 2022 May 20;12(5):80
MEC-1 cells (overexpressing BTKC481S) 0.01, 0.1, 1 µM 1 hour Evaluate the inhibitory effect of Pirtobrutinib on the BCR signaling pathway; results showed that Pirtobrutinib inhibited phosphorylation of BTKC481S at 0.1 µM Blood Cancer J. 2022 May 20;12(5):80
MEC-1 cells (overexpressing BTKWT) 0.01, 0.1, 1 µM 1 hour Evaluate the inhibitory effect of Pirtobrutinib on the BCR signaling pathway; results showed that Pirtobrutinib inhibited phosphorylation of BTKWT at 0.01 µM Blood Cancer J. 2022 May 20;12(5):80
BTK C481S CLL cells 0.6 µM 1 hour To evaluate the inhibitory effect of Pirtobrutinib on BCR signaling in BTK C481S mutant CLL cells. Results showed that Pirtobrutinib significantly inhibited phospho-BTK and PLCγ2, while ibrutinib and acalabrutinib had weaker inhibitory effects. Blood Adv. 2023 May 9;7(9):1929-1943
BTK WT CLL cells 1.2 to 300 nM 1 hour To evaluate the inhibitory effect of Pirtobrutinib on BCR signaling in BTK WT CLL cells. Results showed that Pirtobrutinib effectively inhibited phospho-BTK (IC50 of 1.1 nM) and phospho-PLCγ2. Blood Adv. 2023 May 9;7(9):1929-1943
HEK293 BTK WT and HEK293 BTK C481S cells 1.2 to 300 nM 2 hours To evaluate the inhibitory effect of Pirtobrutinib on BTK WT and C481S mutations in HEK293 cells. Results showed that Pirtobrutinib inhibited both BTK WT and C481S mutations (IC50 of 4.2 nM and 16 nM, respectively), while ibrutinib was ineffective against the C481S mutation. Blood Adv. 2023 May 9;7(9):1929-1943
Primary CLL cells (harboring BTKWT or mutant BTK) 0.1, 1 µM 24 hours Evaluate the inhibitory effect of Pirtobrutinib on the BCR signaling pathway in primary CLL cells; results showed that Pirtobrutinib inhibited BTK phosphorylation in all samples Blood Cancer J. 2022 May 20;12(5):80
Platelets 30-0.03 µM 3 minutes To evaluate the effect of Pirtobrutinib on Src Y418 phosphorylation, results showed that Pirtobrutinib did not cause dose-dependent inhibition of SFK activity. Haematologica. 2023 May 1;108(5):1429-1435
Mino-venetoclax-R cells 15 µM 72 hours To test the cytotoxicity of Pirtobrutinib and venetoclax combination on venetoclax-resistant MCL cell lines Haematologica. 2023 May 1;108(5):1412-1416
JeKo-ibrutinib-R cells 15 µM 72 hours To test the cytotoxicity of Pirtobrutinib and venetoclax combination on ibrutinib-resistant MCL cell lines Haematologica. 2023 May 1;108(5):1412-1416
JeKo-1 cells 7.5 µM 72 hours To test the cytotoxicity of Pirtobrutinib and venetoclax combination on MCL cell lines Haematologica. 2023 May 1;108(5):1412-1416

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NSG mice Subcutaneous cell line–derived xenograft (CDX) models Oral 30 mg/kg Twice daily, continuous treatment Pirtobrutinib in combination with safimaltib significantly inhibited tumor growth in IBN-R PDX models and prolonged mouse survival J Clin Invest. 2023 Feb 1;133(3):e165694
NSG mice Patient-derived xenograft model Oral gavage 50 mg/kg (Pirtobrutinib), 10 mg/kg (venetoclax) Twice daily (Pirtobrutinib), once daily (venetoclax), for 85 days To test the in vivo anti-tumor efficacy of Pirtobrutinib and venetoclax combination on dual-resistant MCL Haematologica. 2023 May 1;108(5):1412-1416

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT06390956 Marginal Zone Lymphoma PHASE2 RECRUITING 1932-12-01 Huntsman Cancer Institute at U... More >>niversity of Utah, Salt Lake City, Utah, 84112, United States Less <<
NCT05172700 Leukemia, Lymphocytic, Chronic... More >>, B-Cell|Lymphoma, Lymphocytic, Small|Lymphoma, Mantle-Cell|Waldenstrom Macroglobulinemia|Ritcher's Transformation, Syndrome Less << APPROVED_FOR_MARKETING - -
NCT06190678 Healthy|Renal Insufficiency PHASE1 COMPLETED 2021-06-04 Orange County Research Institu... More >>te, Anaheim, California, 92801, United States|Riverside Clinical Research, Edgewater, Florida, 32132, United States|Clinical Pharmacology of Miami, Miami, Florida, 33014, United States|Orlando Clinical Research Center, Orlando, Florida, 32809, United States|Prism Research, Saint Paul, Minnesota, 55114, United States Less <<
NCT06190691 Healthy|Hepatic Insufficiency PHASE1 COMPLETED 2021-12-30 Orange County Research Institu... More >>te, Anaheim, California, 92801, United States|Orange County Research Center, Tustin, California, 92780, United States|Riverside Clinical Research, Edgewater, Florida, 32132, United States|Clinical Pharmacology of Miami, Miami, Florida, 33014, United States|Advanced Pharma Clinical Research, Miami, Florida, 33147, United States|Orlando Clinical Research Center, Orlando, Florida, 32809, United States|The Texas Liver Institute, San Antonio, Texas, 78215, United States|Pinnacle Clinical Research, San Antonio, Texas, 78229, United States Less <<
NCT06588478 Chronic Lymphocytic Leukemia|S... More >>mall Lymphocytic Lymphoma Less << PHASE2 RECRUITING 2025-12-28 Ironwood Cancer & Research Cen... More >>ters, Chandler, Arizona, 85224, United States|City of Hope National Medical Center, Duarte, California, 91010, United States|City of Hope National Medical Center, Irvine, California, 92618, United States|Palo Alto Medical Foundation Research Institute (PAMFRI), Palo Alto, California, 94304, United States|Stanford Cancer Center, Palo Alto, California, 94304, United States|Rocky Mountain Cancer Center, Aurora, Colorado, 80012, United States|University of Miami Hospital and Clinics, Sylvester Cancer Center, Miami, Florida, 33136, United States|Mission Cancer + Blood, Des Moines, Iowa, 50309, United States|Saint Elizabeth Medical Center Edgewood, Edgewood, Kentucky, 41017, United States|American Oncology Partners of Maryland, PA, Bethesda, Maryland, 20817, United States|Boston Medical Center, Boston, Massachusetts, 02118, United States|Gulfport Memorial Hospital, Gulfport, Mississippi, 39501, United States|Clinical Research Alliance, Westbury, New York, 11590, United States|East Carolina University, Greenville, North Carolina, 27834, United States|Williamette Valley Cancer Institute & Research Center, Eugene, Oregon, 97401, United States|Cancer Care Associates Of York, York, Pennsylvania, 17403, United States|The West Clinic, PLLC dba West Cancer Center, Germantown, Tennessee, 38138, United States|Sarah Cannon Research Institute/SCRI, Nashville, Tennessee, 37203, United States|USO-Texas Oncology-Central/South Texas, Austin, Texas, 78705, United States|USO-Virginia Oncology Associates, Hampton, Virginia, 23666, United States|USO-Northwest Cancer Specialists, PC, Vancouver, Washington, 98683, United States|Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, United States|Bankstown-Lidcombe Hospital, Bankstown, New South Wales, 2200, Australia|Coffs Harbour Health Campus, Coffs Harbour, New South Wales, 2450, Australia|Calvary Mater Newcastle, Waratah, New South Wales, 2298, Australia|Princess Alexandra Hospital, Woolloongabba, Queensland, 4102, Australia|ICON Cancer Centre - Kurralta Park, Kurralta Park, South Australia, 5037, Australia|Royal Hobart Hospital, Hobart, Tasmania, 7000, Australia|Box Hill Hospital, Box Hill, Victoria, 3128, Australia|Latrobe Regional Health, Traralgon, Victoria, 3844, Australia|The Perth Blood Institute - West Perth, West Perth, Western Australia, 6005, Australia|Clinique Saint Pierre, Ottignies, Brabant Wallon, 1340, Belgium|Institut Jules Bordet, Anderlecht, Bruxelles-Capitale, Région De, 1070, Belgium|Groupe Jolimont, La Louvière, Hainaut, 7100, Belgium|CHR Verviers - La Tourelle, Verviers, Liège, 4800, Belgium|UZ Gent, Gent, Oost-Vlaanderen, 9000, Belgium|AZ Nikolaas, Sint-Niklaas, Oost-Vlaanderen, B-9100, Belgium|UZ Leuven, Leuven, Vlaams-Brabant, 3000, Belgium|AZ Sint-Jan Brugge-Oostende AV, Brugge, West-Vlaanderen, 8000, Belgium|AZ Delta vzw, Roeselare, West-Vlaanderen, 8800, Belgium|Royal Victoria Regional Health Centre, Barrie, Ontario, L4M 6M2, Canada|CIUSSS- saguenay-Lac-Saint-Jean, Chicoutimi, Quebec, G7H 5H6, Canada|Saskatoon Cancer Centre, Saskatoon, Saskatchewan, S7N4H4, Canada|Fakultní nemocnice Brno Bohunice, Brno, Brno-město, 625 00, Czechia|Fakultni nemocnice Hradec Kralove, Hradec Kralove, Hradec Králové, 500 05, Czechia|Fakultni nemocnice Kralovske Vinohrady, PRague, Praha 10, 100 34, Czechia|Vseobecna fakultni nemocnice v Praze, Praha 2, 12808, Czechia|Aarhus Universitetshospital, Skejby, Aarhus, Midtjylland, 8200, Denmark|Roskilde Sygehus, Roskilde, Sj?lland, 4000, Denmark|Odense Universitetshospital, Odense, Syddanmark, 5000, Denmark|Centre Antoine-Lacassagne, Nice, Alpes-Maritimes, 06189, France|Groupe Hospitalier de la Région de Mulhouse et Sud Alsace - H?pital Emile Muller, Mulhouse, Alsace, 68100, France|Centre Hospitalier Universitaire de Caen - H?pital C?te de Nacre, Caen, Calvados, 14033, France|Institut Universitaire du Cancer Toulouse - Oncopole - CHU de TOULOUSE, Toulouse, Haute-Garonne, 31059, France|Centre Hospitalier Régional Universitaire de Tours - H?pital Bretonneau, Tours, Indre-et-Loire, 37044 Cedex 9, France|Centre Hospitalier du Mans, Le Mans, Sarthe, 72000, France|Centre Hospitalier d'Argenteuil Victor Dupouy, Argenteuil, Val-d'Oise, 95107, France|Klinikum Aschaffenburg-Alzenau, Aschaffenburg, Bayern, 63739, Germany|Centrum für H?matologie und Onkologie Bethanien, Frankfurt, Hessen, 60389, Germany|OSP G?ttingen, Goettingen, Niedersachsen, 37073, Germany|Onkologisches Ambulanzzentrum Hannover, Hannover, Niedersachsen, 30171, Germany|Gemeinschaftspraxis für H?matologie und Onkologie Münster, Münster, Nordrhein-Westfalen, 48153, Germany|InVO Institut für Versorgungsforschung in der Onkologie, Koblenz, Rheinland-Pfalz, 56068, Germany|Evangelismos General Hospital of Athens, Athens, Attikí, 106 76, Greece|Attikon General University Hospital, Chaidari, Attikí, 12462, Greece|General Hospital of Athens "Laiko", Αthens, Attikí, 11527, Greece|G. Papanikolaou General Hospital, Thessaloniki, Thessaloníki, 570 10, Greece|Pécsi Tudományegyetem Klinikai K?zpont, Pécs, Baranya, 7624, Hungary|Szegedi Tudományegyetem Szent-Gy?rgyi Albert Klinikai K?zpont, Szeged, Csongrád, 6725, Hungary|Semmelweis University, Budapest, 1088, Hungary|Dél-Pesti Centrumkórház, Budapest, 1097, Hungary|Azienda Ospedaliero Universitaria S.Anna, Cona, Emilia-Romagna, 44124, Italy|Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore, Roma, Lazio, 00168, Italy|ASST Grande Ospedale Metropolitano Niguarda, Milan, Lombardia, 20162, Italy|A.O.U.C. Policlinico di Bari, Bari, Puglia, 70124, Italy|Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO, Palermo, Sicilia, 90146, Italy|Azienda Ospedaliera Universitaria Careggi, Firenze, Toscana, 50134, Italy|AO Santa Maria della Misericordia, Perugia, Umbria, 06132, Italy|Azienda Ospedale - Università Padova, Padova, Veneto, 35128, Italy|Azienda Ospedaliero Universitaria Maggiore della Carità, Novara, 28100, Italy|AOU Policlinico Umberto I, Roma, 00161, Italy|Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonranamdo, 58128, Korea, Republic of|Seoul National University Hospital, Seoul, Seoul-teukbyeolsi [Seoul], 03080, Korea, Republic of|Severance Hospital, Yonsei University Health System, Seoul, Seoul-teukbyeolsi [Seoul], 03722, Korea, Republic of|Samsung Medical Center, Seoul, Seoul-teukbyeolsi [Seoul], 06351, Korea, Republic of|The Catholic Univ. of Korea Seoul St. Mary's Hospital, Seoul, Seoul-teukbyeolsi [Seoul], 06591, Korea, Republic of|The Catholic University of Korea, Yeouido St. Mary's Hospital, Seoul, Seoul-teukbyeolsi [Seoul], 07345, Korea, Republic of|Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroc?awiu, Wroc?aw, Dolno?l?skie, 50-367, Poland|Szpital Uniwersytecki Nr 2 im. dr J. Biziela w Bydgoszczy, Bydgoszcz, Kujawsko-pomorskie, 85-168, Poland|Pratia MCM Krakow, Kraków, Ma?opolskie, 30-727, Poland|AIDPORT Sp. z o.o., Skórzewo, Wielkopolskie, 60-185, Poland|Pratia Onkologia Katowice, Katowice, ?l?skie, 40-519, Poland|Fundeni Clinical Institute, Bucuresti, Bucure?ti, 022328, Romania|Ovidius Clinical Hospital OCH, Ovidiu, Constan?a, 905900, Romania|Spitalul Clinic Municipal Filantropia Craiova, Craiova, Dolj, 200143, Romania|Spitalul Clinic Col?ea, Bucure?ti, 030171, Romania|Institutul Oncologic Cluj, Cluj, 400015, Romania|Institutul Regional de Oncologie, Ia?i, 700483, Romania|Fakultna nemocnica s poliklinikou F.D.Roosevelta Banska Bystrica, Banska Bystrica, Banskobystricky Kraj, 975 17, Slovakia|Narodny onkologicky ustav, Bratislava, Bratislavsky Kraj, 833 10, Slovakia|Univerzitna Nemocnica L. Pasteura Kosice, Kosice, Ko?icky Kraj, 040 11, Slovakia|Univerzitna nemocnica Martin, Martin, ?ilinsky Kraj, 036 59, Slovakia|Hospital Universitario Virgen Macarena, Sevilla, Andalucía, 41009, Spain|Hospital Universitario Central de Asturias, Oviedo, Asturias, 33011, Spain|Institut Català d'Oncologia (ICO) - Badalona, Badalona, Barcelona [Barcelona], 08916, Spain|Hospital Universitari Vall d'Hebron, Barcelona, Barcelona [Barcelona], 08035, Spain|Institut Català d'Oncologia - L'Hospitalet, L'Hospitalet Del Llobregat, Barcelona [Barcelona], 08908, Spain|Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, 39008, Spain|Hospital Clínic de Barcelona, Barcelona, Catalunya [Catalu?a], 08036, Spain|Clinica Universidad de Navarra, Madrid, Madrid, Comunidad De, 28027, Spain|Hospital Universitario Infanta Leonor, Madrid, Madrid, Comunidad De, 28031, Spain|MD Anderson Cancer Center, Madrid, Madrid, Comunidad De, 28033, Spain|Hospital Universitario Ramón y Cajal, Madrid, Madrid, Comunidad De, 28034, Spain|Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Comunidad De, 28222, Spain|Hospital Costa del Sol, Marbella, Málaga, 29603, Spain|Hospital Universitario 12 de Octubre, Madrid, 28041, Spain|Hospital Universitario Quironsalud Madrid, Madrid, 28223, Spain|Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca, Salamanca, 37007, Spain|Hospital Universitario Virgen Del Rocio, Sevilla, 41013, Spain|Kocaeli üniversitesi, Izmit, Kocaeli, 41380, Turkey|Sakarya University School of Medicine, Adapazar?, Sakarya, 54100, Turkey|Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arast?rma Hastanesi, Ankara, 06200, Turkey|Ankara University Health Practice and Research Hospitals, Ankara, 06620, Turkey|Memorial Antalya Hospital, Antalya, 07090, Turkey|Yeditepe üniversitesi Ko?uyolu Hastanesi, Istanbul, 34718, Turkey|Ege Universitesi Hastanesi, Izmir, 35100, Turkey|VM Medical Park Mersin Hastanesi, Mersin, 33200, Turkey|Ondokuz May?s Universitesi, Samsun, 55139, Turkey|Maidstone Hospital, Maidstone, Kent, ME16 9QQ, United Kingdom|Lincoln County Hospital, Lincoln, Lincolnshire, LN2 5QY, United Kingdom|Northwick Park Hospital, Harrow, London, City Of, HA1 3UJ, United Kingdom|Hammersmith Hospital, London, London, City Of, W12 0HS, United Kingdom|Heartlands Hospital, Birmingham, B9 5SS, United Kingdom|The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, United Kingdom|St James's University Hospital, Leeds, LS9 7TF, United Kingdom|Clatterbridge Cancer Centre - Liverpool, Liverpool, L7 8YA, United Kingdom|Singleton Hospital, Swansea, SA2 8QA, United Kingdom Less <<
NCT06181006 Healthy PHASE1 COMPLETED 2020-12-01 Covance Clinical Research Unit... More >>, Daytona Beach, Florida, 32117, United States Less <<
NCT06812715 Chronic Lymphocytic Leukemia PHASE2 NOT_YET_RECRUITING 2025-05-31 Peter MacCallum Cancer Centre,... More >> Melbourne, Victoria, 3000, Australia|Alfred Hospital, Melbourne, Victoria, 3004, Australia|Monash Medical Centre, Melbourne, Victoria, 3168, Australia Less <<
NCT06180980 Healthy PHASE1 COMPLETED 2021-03-08 Covance Clinical Research Unit... More >>, Daytona Beach, Florida, 32117, United States Less <<
NCT06258174 Healthy PHASE1 COMPLETED 2021-12-22 Labcorp Drug Development, Dall... More >>as, Texas, 75247, United States Less <<
NCT04849416 Leukemia, Lymphoid|Lymphoma, N... More >>on-Hodgkin|Lymphoma, Mantle-Cell|Lymphoma, Large B-Cell, Diffuse|Lymphoma, B-Cell|Lymphoma, B-Cell, Marginal Zone|Leukemia, Lymphocytic, Chronic, B-Cell Less << PHASE2 ACTIVE_NOT_RECRUITING 2025-04-25 Wannan Medical College Yijisha... More >>n Hospital, Wuhu, Anhui, 241001, China|Beijing Cancer hospital, Beijing, Beijing, 100142, China|Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, 510515, China|Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 511400, China|Hainan General Hospital, Haikou, Hainan, 570311, China|Affiliated Hospital of Hebei University, Baoding, Hebei, 71066, China|Xingtai People's Hospital, Xingtai, Hebei, 054031, China|Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, China|The First Affiliated Hospital of Henan University of Science &Technology, Luoyang Shi, Henan, 471003, China|Henan Cancer Hospital, Zhengzhou, Henan, 450008, China|Xiangya Hospital Central South University, Changsha, Hunan, 410008, China|Hunan Cancer Hospital, Changsha, Hunan, 410013, China|Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210000, China|The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215066, China|The First Hospital of Jilin University, Changchun, Jilin, 130021, China|Xi'an International Medical Center Hospital, Xi'an, Shaanxi, 710126, China|Sichuan Cancer Hospital, Chengdu, Sichuan, 610041, China|Institute of hematology&blood disease hospital, Tianjin, Tianjin, 300020, China|Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin, 300060, China|Xinjiang Medical University Cancer Hospital - Urumqi, Urumqi, Xinjiang, 830000, China|Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China|Shanghai East Hospital, Shanghai, 200120, China Less <<

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