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Chemical Structure| 1421373-65-0 Chemical Structure| 1421373-65-0

Structure of Osimertinib
CAS No.: 1421373-65-0

Chemical Structure| 1421373-65-0

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Osimertinib (AZD9291) is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M. It overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.

Synonyms: AZD-9291; Mereletinib

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Product Details of Osimertinib

CAS No. :1421373-65-0
Formula : C28H33N7O2
M.W : 499.61
SMILES Code : C=CC(NC1=CC(NC2=NC=CC(C3=CN(C)C4=C3C=CC=C4)=N2)=C(OC)C=C1N(CCN(C)C)C)=O
Synonyms :
AZD-9291; Mereletinib
MDL No. :MFCD27988062
InChI Key :DUYJMQONPNNFPI-UHFFFAOYSA-N
Pubchem ID :71496458

Safety of Osimertinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Osimertinib

RTK
JAK-STAT

Isoform Comparison

Biological Activity

Target
  • EGFR/ErbB1

    WT EGFR, IC50:12.92 nM

    L858R/T790M EGFR, IC50:11.44 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
H1975 1 μM 9 days Generate osimertinib-resistant cell lines PMC6324945
PC9 1 μM 9 days Generate osimertinib-resistant cell lines PMC6324945
HCC827 100 nM 21 days To observe the metabolic changes in osimertinib-tolerant cells, significant changes in metabolite levels were found PMC6750230
HCC827 160 nM 2–3 weeks To observe the survival of cells under continuous dosing, it was found that some cells survived for 2–3 weeks at 160 nM osimertinib PMC6750230
HCC827 0.01–2 µM 3 days To observe the acute treatment response of cells to osimertinib, it was found that a subpopulation of tumor cells survived cytotoxic doses PMC6750230
HCC827 2 nM 72 h To evaluate the antiproliferative activity of ASK120067 on EGFR exon19 deletion mutant cells, the results showed that ASK120067 significantly inhibited the proliferation of HCC827 cells with an IC50 value of 2 nM. PMC7218543
PC-9 6 nM 72 h To evaluate the antiproliferative activity of ASK120067 on EGFR exon19 deletion mutant cells, the results showed that ASK120067 significantly inhibited the proliferation of PC-9 cells with an IC50 value of 6 nM. PMC7218543
NCI-H1975 12 nM 72 h To evaluate the antiproliferative activity of ASK120067 on EGFR T790M mutant cells, the results showed that ASK120067 significantly inhibited the proliferation of NCI-H1975 cells with an IC50 value of 12 nM. PMC7218543
HCC2935 500 nM 21 days To identify gene expression changes in osimertinib DTPs, finding distinct gene expression patterns in DTPs compared to acute treatment. PMC9794691
HCC827 500 nM 21 days To identify gene expression changes in osimertinib DTPs, finding distinct gene expression patterns in DTPs compared to acute treatment. PMC9794691
H1975 500 nM 21 days To identify gene expression changes in osimertinib DTPs, finding distinct gene expression patterns in DTPs compared to acute treatment. PMC9794691
PC9 500 nM 21 days To identify gene expression changes in osimertinib DTPs, finding distinct gene expression patterns in DTPs compared to acute treatment. PMC9794691
DFCI161 1 μM 16 h To evaluate the effect of Osimertinib on downstream signaling pathways in DFCI161 cells, results showed that single-agent MET inhibitor was sufficient to inhibit downstream Akt and ERK1/2 phosphorylation. PMC8627689
DFCI81 1 μM 16 h To evaluate the effect of Osimertinib on downstream signaling pathways in DFCI81 cells, results showed that single-agent MET inhibitor was sufficient to inhibit downstream Akt and ERK1/2 phosphorylation. PMC8627689

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice PC9-OR cell xenograft model Oral 5 mg/kg Once daily for 71 days Evaluate the tumor growth inhibitory effect of osimertinib in combination with Aurora kinase inhibitors PMC6324945
Mice Subcutaneous tumor model Subcutaneous injection 100 nM 21 days To observe the metabolic changes in osimertinib-tolerant cells, significant changes in metabolite levels were found PMC6750230
BALB/c nude mice NCI-H1975 xenograft model Oral 1, 5, 10 mg/kg Once daily for 21 days To evaluate the in vivo antitumor activity of ASK120067 in the NCI-H1975 xenograft model, the results showed that ASK120067 dose-dependently inhibited tumor growth, with a tumor growth inhibition (TGI) rate of 99.3% at the 10 mg/kg dose. PMC7218543
Mice H1975 xenograft model Oral 25 mg/kg Once daily for 3 weeks To evaluate the delay in tumor regrowth with Osimertinib in combination with AZD2811 (AURKB inhibitor). PMC9794691
Mice Non-small cell lung cancer xenograft model Oral 5 mg/kg Once daily for 95 days To investigate the anti-tumor effects and resistance mechanisms of Osimertinib in EGFR L858R and T790M mutant xenograft models. Results showed that Osimertinib significantly inhibited tumor growth initially, but resistance developed after prolonged treatment, associated with secondary mutations in BRAF and PIK3C2A and decreased frequencies of EGFR L858R and T790M mutations. PMC5993147
Mice Orthotopic NSCLC model Oral 3.125 mg/kg Once daily, 5/7 days To evaluate the combination of osimertinib and AZ1366 for tumor control and survival improvement in Wnt-responsive tumors. Results showed that the combination of osimertinib and AZ1366 significantly improved survival in Wnt-responsive HCC4006 and H1650 cell lines. PMC5354947
Mice PDX model Oral 25 mg/kg Once daily for 28 days To evaluate the antitumor efficacy of Osimertinib in PDX models, results showed that single-agent MET inhibitor was sufficient to inhibit tumor growth, and the addition of an EGFR inhibitor did not significantly enhance efficacy. PMC8627689

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT05103605 Non Small Cell Lung Cancer ACTIVE_NOT_RECRUITING 2026-01-15 Research Site, Abbeville Cedex... More >>, France|Research Site, Aix En Provence Cedex 1, France|Research Site, Angers Cedex 01, France|Research Site, Antibes Cedex, France|Research Site, Avignon Cedex 9, France|Research Site, Bastia Cedex, France|Research Site, Bayonne, France|Research Site, Bordeaux Cedex, France|Research Site, Bourg En Bresse, France|Research Site, Brest, France|Research Site, Cannes Cedex, France|Research Site, Chambery Cedex, France|Research Site, Chauny Cedex, France|Research Site, Cholet, France|Research Site, Clermont-ferrand, France|Research Site, Colmar Cedex, France|Research Site, Contamine-sur-arve, France|Research Site, Creteil, France|Research Site, Elbeuf Cedex, France|Research Site, Epagny METZ Tessy, France|Research Site, Evreux, France|Research Site, La Roche Sur Yon, France|Research Site, Libourne, France|Research Site, Limoges Cedex, France|Research Site, Lyon, France|Research Site, Marseille Cedex 08, France|Research Site, Marseille, France|Research Site, Meaux Cedex, France|Research Site, Mulhouse, France|Research Site, Orleans, France|Research Site, Paris, France|Research Site, Poitiers Cedex, France|Research Site, Quimper, France|Research Site, Reims Cedex, France|Research Site, Rouen Cedex, France|Research Site, Saint Denis, France|Research Site, Saint Pierre, France|Research Site, Saint Priest En Jarez Cedex, France|Research Site, Saint-gregoire, France|Research Site, Saint-quentin Cedex, France|Research Site, Toulon Cedex 9, France|Research Site, Toulouse Cedex 9, France|Research Site, Valenciennes, France|Research Site, Vannes, France|Research Site, Villefranche-sur-saone, France|Research Site, Villenave-dornon, France|Research Site, Villeurbanne, France Less <<
NCT04233021 Non Small Cell Lung Cancer Met... More >>astatic|Leptomeningeal Metastasis|Brain Metastases|EGFR Activating Mutation Less << PHASE2 COMPLETED 2024-12-27 Centre Hospitalier Aix-Pertuis... More >>, Aix-en-Provence, 13616, France|CHU Amiens - Groupe Hospitalier Sud, Amiens, 80054, France|Centre Paul Papin, Angers, 49055, France|H?pital privé d'Antony, Antony, 92166, France|Institut Sainte Catherine, Avignon, 84918, France|Centre Hospitalier de la C?te Basque, Bayonne, 64100, France|CHU Besan?on - H?pital J. MINJOZ, Besan?on, 25030, France|Groupe Hospitalier Saint André, Bordeaux, 33075, France|AP-HP H?pital Ambroise Paré, Boulogne, 92104, France|CHU C?te de Nacre, Caen, 14000, France|H?pital Louis Pasteur, Colmar, 68024, France|Centre Hospitalier Intercommunal de Créteil, Créteil, 94000, France|CHU H?pital du Bocage, Dijon, 21079, France|Chu Grenoble, Grenoble, 38043, France|Centre Hospitalier Général, Le Mans, 72037, France|H?pital Calmette, Lille, 59037, France|CHU Dupuytren, Limoges, 87042, France|Institut Paoli Calmettes, Marseille, 13273, France|Marseille H?pital Nord, Marseille, 13915, France|CHU Montpellier, Montpellier, 34295, France|Centre Hospitalier Régional - H?pital de la Source, Orléans, 45000, France|AP-HP H?pital Cochin, Paris, 75014, France|AP-HP H?pital Bichat, Paris, 75877, France|Centre Hospitalier Général - Pau, Pau, 64000, France|Lyon - URCOT Centre Hospitalier Universitaire, Pierre-Bénite, 69310, France|CHU de la Réunion - Site Felix Guyon, Saint-Denis, 97400, France|Institut de Cancérologie de l'Ouest - René Gauducheau, Saint-Herblain, 44805, France|CHU de La Réunion-Site Sud, Saint-Pierre, 97448, France|Nouvel H?pital Civil - H?pitaux Universitaires de Strasbourg, Strasbourg, 67091, France|H?pital Foch, Suresnes, 92151, France|HIA Sainte-Anne, Toulon, 83800, France|H?pital Larrey, Toulouse, 31059, France|CHU Bretonneau, Tours, 37044, France|Valenciennes Clinique PRIV, Valenciennes, 59300, France|Centre Hospitalier de Villefranche-sur-Sa?ne, Villefranche-sur-Sa?ne, 69655, France|Gustave Roussy, Villejuif, 94805, France Less <<
NCT05546866 Non-small Cell Lung Cancer PHASE2 ACTIVE_NOT_RECRUITING 2029-06-30 Research Site, Beijing, 100730... More >>, China|Research Site, Chengdu, 610000, China|Research Site, Chengdu, 610041, China|Research Site, Fuzhou, 350011, China|Research Site, Guangzhou, 510080, China|Research Site, Kunming, 650118, China|Research Site, Ningbo, 315010, China|Research Site, Shijiazhuang, 050051, China|Research Site, Suzhou, 215006, China|Research Site, Tianjin, 300060, China Less <<
NCT06206850 Non-squamous NSCLC PHASE2 RECRUITING 2030-01-01 Sheba Medical Center, Jusidman... More >> Cancer Center, Ramat Gan, 5590000, Israel|Sheba Medical Center, Ramat-gan, 522651, Israel Less <<
NCT06477055 Non-small Cell Lung Cancer PHASE2 NOT_YET_RECRUITING 2027-06-15 -
NCT04391283 Carcinoma, Non-Small-Cell Lung UNKNOWN 2025-12-24 The First Affiliated Hospital ... More >>of College of Medicine Zhejiang University, Hangzhou, Zhejiang, 310000, China Less <<
NCT03535363 NSCLC|Non-small Cell Lung Canc... More >>er Less << PHASE1 COMPLETED 2022-04-01 Maimi Cancer Institute - Bapti... More >>st Health South Florida, Miami, Florida, 33176, United States|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center, Cleveland, Ohio, 44195, United States Less <<
NCT05785208 Non Small Cell Lung Cancer PHASE4 RECRUITING 2025-10-31 Azienda Ospedaliero-Universita... More >>ria Ospedali Riuniti, Ancona, 60020, Italy|IRCCS Istituto Tumori Giovanni Paolo II, Bari, 70124, Italy|Azienda Ospedaliero-Universitaria Careggi, Firenze, 50134, Italy|Ospedale Universitario di Parma, Parma, 44129, Italy|Ospedale San Camillo de Lellis, Rieti, 02100, Italy|Università Policlinico Tor Vergata, Rome, 00133, Italy|Policlinico Umberto I, Rome, 00161, Italy|Fondazione Policlinico Gemelli IRCCS, Rome, 00168, Italy|Ospedale San Giovanni-Addolorata, Rome, 00184, Italy|Ospedale San Luigi, Turin, 10043, Italy|Università degli Studi di Verona, Verona, 37129, Italy Less <<
NCT03219970 Non-small Cell Lung Cancer COMPLETED 2020-10-28 Pamela Youde Nethersole Easter... More >>n Hospital, Hong Kong, China|Prince of wales hospital, Hong Kong, China|Queen Mary Hospital, Hong Kong, China|Tuen Mun Hospital, Hong Kong, China Less <<
NCT02841579 Non-Small Cell Lung Cancer PHASE2 COMPLETED 2020-02-14 MedSIR Investigative Site, Bar... More >>celona, 08026, Spain|MedSIR Investigative Site, Barcelona, 08028, Spain|MedSIR Investigative Site, Bilbao, 48903, Spain|MedSIR Investigative Site, La Coru?a, 15706, Spain|MedSIR Investigative Site, Madrid, 28006, Spain|MedSIR Investigative Site, Málaga, 29010, Spain|MedSIR Investigative Site, Valencia, 46015, Spain Less <<
NCT03586453 Carcinoma, Non-Small-Cell Lung PHASE2 ACTIVE_NOT_RECRUITING 2027-03-01 Beth Israel Deaconess Medical ... More >>Center, Boston, Massachusetts, 02215, United States|Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States Less <<
NCT05629234 Cancer PHASE3 ACTIVE_NOT_RECRUITING 2025-02-21 Research Site, Beijing, 100142... More >>, China|Research Site, Chongqing, 400042, China|Research Site, Shanghai, 200433, China|Research Site, Yangzhou, 225001, China|Research Site, Zhengzhou, 450008, China|Research Site, Villejuif Cedex, 94805, France|Research Site, Cheongju-si, 28644, Korea, Republic of|Research Site, Dong-gu, 44033, Korea, Republic of|Research Site, Goyang-si, 10408, Korea, Republic of|Research Site, Seongnam-si, 13620, Korea, Republic of|Research Site, Seoul, 03080, Korea, Republic of|Research Site, Seoul, 03722, Korea, Republic of|Research Site, Seoul, 06351, Korea, Republic of|Research Site, Seoul, 06591, Korea, Republic of|Research Site, Seoul, 5505, Korea, Republic of|Research Site, Georgetown, 10450, Malaysia|Research Site, Johor Bahru, 81100, Malaysia|Research Site, Kuantan, 25100, Malaysia|Research Site, Kuching, 93586, Malaysia|Research Site, Szczecin, 70-419, Poland|Research Site, Kaohsiung, 83301, Taiwan|Research Site, Taichung, 40705, Taiwan|Research Site, Tainan, 704, Taiwan|Research Site, Tainan, 736, Taiwan|Research Site, Taipei, 112201, Taiwan|Research Site, Taoyuan, 333, Taiwan|Research Site, Nottingham, NG5 1PB, United Kingdom Less <<
NCT03790397 Non Small Cell Lung Cancer COMPLETED 2020-04-01 Hospital Universitario Central... More >> de Asturias, Oviedo, Asturias, 33011, Spain|ICO Badalona, Badalona, Barcelona, 08916, Spain|Hospital Clínico Universitario de Santiago, Santiago De Compostela, Galicia, 15706, Spain|Complejo Hospitalario Universitario A Coru?a, A Coru?a, La Coru?a, 15006, Spain|Hospital Universitario Dr. Negrín, Las Palmas De Gran Canaria, Las Palmas, 35010, Spain|Hospital Príncipe de Asturias, Alcalá De Henares, Madrid, 28805, Spain|Hospital Universitario de Getafe, Getafe, Madrid, 28905, Spain|Hospital Universitari Son Espases, Palma de Mallorca, Mallorca, 07120, Spain|Hospital Universitario Son Llàtzer, Palma De Mallorca, Mallorca, 07198, Spain|Complejo Hospitalario Universitario de Vigo, Vigo, Pontevedra, 36036, Spain|Hospital Lluís Alcanyís, Xàtiva, Valencia, 46800, Spain|Hospital General de Albacete, Albacete, 02006, Spain|Hospital General Universitario Alicante, Alicante, 03010, Spain|Hospital de Sant Pau, Barcelona, 08041, Spain|Hospital Universitario de Burgos, Burgos, 09006, Spain|Hospital Dr. Josep Trueta, Girona, 17007, Spain|Hospital Universitario de Guadalajara, Guadalajara, 19002, Spain|Complejo Hospitalario de Jaén, Jaén, 23007, Spain|Complejo Asistencial Universitario de León, León, 24071, Spain|Hospital Universitario Lucus Augusti, Lugo, 27003, Spain|Hospital Ramón y Cajal, Madrid, 28034, Spain|Hospital Clínico San Carlos, Madrid, 28040, Spain|Hospital Universitario Puerta de Hierro, Madrid, 28222, Spain|Hospital General Universitario de Málaga, Málaga, 29010, Spain|Hospital Clínico de Salamanca, Salamanca, 37007, Spain|Hospital Virgen del Rocío, Sevilla, 41013, Spain|Hospital Virgen de la Salud, Toledo, 45071, Spain|Hospital Universitari i Politécnic La Fe, Valencia, 46009, Spain|Hospital General Universitario de Valencia, Valencia, 46014, Spain|Hospital Clínico Universitario de Valladolid, Valladolid, 47003, Spain|Hospital Clínico Lozano Blesa, Zaragoza, 50009, Spain Less <<
NCT05421936 Carcinoma, Non-Small-Cell Lung... More >>|Genes, erbB-1 Less << SUSPENDED 2025-09-24 Sheba Medical Centre, Ramat Ga... More >>n, 5265601, Israel Less <<
NCT06383728 Lung Cancer|Carcinoma, Squamou... More >>s Cell Less << PHASE2 RECRUITING 2029-04-30 The First Affiliated Hospital ... More >>of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China Less <<
NCT03810066 NSCLC|EGFR T790M|FDG-PET PHASE2 COMPLETED 2022-09-30 Prof. Dr. med. Martin Schuler,... More >> Essen, NRW, 45147, Germany Less <<
NCT06436144 Non Small Cell Lung Cancer|EGF... More >>R Gene Mutation|Non Small Cell Lung Cancer Stage IIIB|Non-small Cell Lung Cancer Stage IV Less << PHASE2 NOT_YET_RECRUITING 2025-12-29 -
NCT03853551 Non Small Cell Lung Cancer (NS... More >>CLC) Less << PHASE4 COMPLETED 2020-04-15 Research Site, Hyderabad, 5000... More >>34, India|Research Site, Hyderabad, 500096, India|Research Site, Kolkata, 700160, India|Research Site, Mumbai, 400012, India|Research Site, Mumbai, 400053, India|Research Site, New Dehli, 110029, India|Research Site, New Delhi, 110085, India Less <<
NCT04816838 Non Small Cell Lung Cancer RECRUITING 2025-10-25 Yonsei University Health Syste... More >>m, Severance Hospital, Seoul, Korea, Republic of Less <<
NCT05458726 EGFR T790M|Osimertinib|Non-sma... More >>ll Cell Lung Cancer|ddPCR Less << PHASE2 UNKNOWN 2022-10-31 Junling Li, Beijing, Beijing, ... More >>100021, China Less <<
NCT05513664 Locally Advanced or Metastatic... More >> Non-Small Cell Lung Cancer|EGFR Exon20 Insertion Mutations Less << UNKNOWN 2025-08-23 Affiliated Hospital of Hebei U... More >>niversity, Baoding, China|Beijing Cancer Hospital, Beijing, China|Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China|Chinese People's Liberation Army General Hospital, Beijing, China|Chongqing Cancer Hospital, Chongqing, China|Southwest Hospital of Army Medical University, Chongqing, China|Fujian Cancer Hospital, Fuzhou, China|Sun Yat-sen University Cancer Center, Guangzhou, China|The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China|The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China|Anhui Cancer Hospital, Hefei, China|Shandong Cancer Hospital, Jinan, China|Nanjing Chest Hospital, Nanjing, China|Fudan University Cancer Hospital, Shanghai, China|Shanghai Chest Hospital, Shanghai, China|Shanxi Provincial People's Hospital, Shanxi, China|The Fourth Hospital of Hebei Medical University, Shijia Zhuang, China|West China Hospital of Sichuan University, Sichuan, China|Shanxi Cancer Hospital, Taiyuan, China|Huazhong University of Science Tongji Hospital, Tongji Medical College, Wuhan, China|Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China|The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China|First Affiliated Hospital of Zhengzhou University, Zhengzhou, China|Henan Cancer Hospital, Zhengzhou, China Less <<
NCT02769286 Lung Neoplasms|EGFR Gene Mutat... More >>ions Less << PHASE2 COMPLETED 2025-05-20 Chonnam National University Hw... More >>asun Hospital, Hwasun, Jeonnam, 58128, Korea, Republic of Less <<
NCT03394118 NSCLC PHASE2 COMPLETED 2021-04-08 Asan Medical Center, Seoul, Ko... More >>rea, Republic of Less <<
NCT05686434 NSCLC, Stage I PHASE2 RECRUITING 2029-10-14 Tianjin Medical University Can... More >>cer Institute & Hospital, Tianjin, Tianjin, 300060, China Less <<
NCT03239340 EGFR Mutation Positive Locally... More >> Advanced or Metastatic Non-Small Cell Lung Cancer Less << PHASE2 COMPLETED 2023-09-19 Research Site, Athens, Georgia... More >>, 30607, United States|Research Site, Atlanta, Georgia, 30307, United States|Research Site, Boston, Massachusetts, 02215, United States|Research Site, Brescia, 25100, Italy|Research Site, Meldola, 47014, Italy|Research Site, Monza, 20900, Italy|Research Site, Parma, 43126, Italy|Research Site, Roma, 00152, Italy|Research Site, Terni, 05100, Italy|Research Site, Busan, 47392, Korea, Republic of|Research Site, Cheongiu, 28644, Korea, Republic of|Research Site, Seongnam, 13620, Korea, Republic of|Research Site, Seoul, 03722, Korea, Republic of|Research Site, Seoul, 05505, Korea, Republic of|Research Site, Seoul, 06591, Korea, Republic of|Research Site, Seoul, 135-710, Korea, Republic of|Research Site, Johor Bahru, 81100, Malaysia|Research Site, Kuantan, 25100, Malaysia|Research Site, Kuching, 93586, Malaysia|Research Site, Lembah Pantai, 59100, Malaysia|Research Site, Pulau Pinang, 10450, Malaysia|Research Site, A Coru?a, 15006, Spain|Research Site, Barcelona, 08035, Spain|Research Site, Las Palmas de Gran Canaria, 35016, Spain|Research Site, Madrid, 28046, Spain|Research Site, Sevilla, 41009, Spain Less <<

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