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Chemical Structure| 1197953-54-0 Chemical Structure| 1197953-54-0
Chemical Structure| 1197953-54-0

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CAS No.: 1197953-54-0

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Brigatinib is a selective ALK inhibitor with IC50 value of 0.37nM, and also inhibits ROS1, FLT3, FLT3-D835Y mutant and EGFR less potently.

Synonyms: AP-26113

4.5 *For Research Use Only !

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Product Details of Brigatinib

CAS No. :1197953-54-0
Formula : C29H39ClN7O2P
M.W : 584.09
SMILES Code : CN1CCN(C2CCN(C3=CC=C(NC4=NC=C(Cl)C(NC5=CC=CC=C5P(C)(C)=O)=N4)C(OC)=C3)CC2)CC1
Synonyms :
AP-26113
MDL No. :MFCD29472221
InChI Key :AILRADAXUVEEIR-UHFFFAOYSA-N
Pubchem ID :68165256

Safety of Brigatinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Brigatinib

RTK

Isoform Comparison

Biological Activity

Target
  • mutant EGFR

    EGFR(del19), IC50:39.9 nM

    EGFR(C797S/T790M/del19), IC50:67.2 nM

  • ALK

    ALK, IC50:0.37 nM

    ROS1, IC50:1.9 nM

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02094573 Carcinoma, Non-Small-Cell Lung PHASE2 COMPLETED 2020-02-27 -
NCT04925609 Anaplastic Large Cell Lymphoma... More >>, ALK-Positive|Inflammatory Myofibroblastic Tumor|Other Solid Tumor Less << PHASE1|PHASE2 RECRUITING 2025-12-30 Institut Gustave Roussy, Paris... More >>, 94805, France|Princess Máxima Center for Pediatric Oncology, Utrecht, 3584 CS, Netherlands Less <<
NCT05100069 Non-small Cell Lung Cancer (NS... More >>CLC) Less << RECRUITING 2027-11-30 Takeda Selected Site, Tokyo, J... More >>apan Less <<
NCT04634110 Brain Metastases|Lung Cancer PHASE2 TERMINATED 2022-04-14 City of Hope, Duarte, Californ... More >>ia, 91010, United States|University of Colorado Hospital, Aurora, Colorado, 80045, United States|Mayo Clinic, Rochester, Minnesota, 55905, United States Less <<
NCT04074993 Non Small Cell Lung Cancer PHASE2 ACTIVE_NOT_RECRUITING 2025-03-31 National Cancer Center, Goyang... More >>-si, Gyeonggi-do, 10408, Korea, Republic of Less <<
NCT03410108 ALK-positive Advanced NSCLC PHASE2 COMPLETED 2021-07-28 Aichi Cancer Center Hospital, ... More >>Nagoya, Aichi, Japan|Nagoya University Hospital, Nagoya, Aichi, Japan|Fujita Health University Hospital, Toyoake, Aichi, Japan|National Cancer Center Hospital East, Kashiwa, Chiba, Japan|National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan|Kurume University Hospital, Kurume, Fukuoka, Japan|Hokkaido Cancer Center, Sapporo, Hokkaido, Japan|Hyogo Cancer Center, Akashi, Hyogo, Japan|Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan|Kanazawa University Hospital, Kanazawa, Ishikawa, Japan|Iwate Medical University Hospital, Morioka, Iwate, Japan|Kanagawa Cancer Center, Yokohama, Kanagawa, Japan|Matsuzaka Citizen's Hospital, Matsuzaka, Mie, Japan|Sendai Kousei Hospital, Sendai, Miyagi, Japan|Kurashiki Central Hospital, Kurashiki, Okayama, Japan|Kansai Medical University Hospital, Hirakata, Osaka, Japan|Kindai University Hospital, Osakasayama, Osaka, Japan|Saitama Cancer Center, Ina, Saitama, Japan|Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan|Jichi Medical University Hospital, Shimotsuke, Tochigi, Japan|Juntendo University Hospital, Bunkyo-ku, Tokyo, Japan|Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan|National Cancer Center Hospital, Chuo-ku, Tokyo, Japan|Cancer Institute Hospital, Koto-ku, Tokyo, Japan|Chiba University Hospital, Chiba, Japan|Kyushu University Hospital, Fukuoka, Japan|National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan|Kyoto University Hospital, Kyoto, Japan|Niigata Cancer Center Hospital, Niigata, Japan|Okayama University Hospital, Okayama, Japan|Osaka City General Hospital, Osaka, Japan|Osaka International Cancer Institute, Osaka, Japan|Wakayama Medical University Hospital, Wakayama, Japan Less <<
NCT05721950 Non-small Cell Lung Cancer (NS... More >>CLC) Less << RECRUITING 2029-12-31 Department of Oncology, Shangh... More >>ai pulmonary hospital, Shanghai, Shanghai, 200433, China Less <<
NCT04223596 Lung Cancer|NSCLC|NSCLC Stage ... More >>IIIB|NSCLC Stage IV Less << PHASE2 ACTIVE_NOT_RECRUITING 2025-04-15 Hospital Regional Universitari... More >>o de Málaga, Málaga, Andalucia, 29010, Spain|ICO Badalona, Badalona, Barcelona, 08916, Spain|ICO Hospitalet, Hospitalet de Llobregat, Barcelona, 08908, Spain|Hospital de la Santa Creu i Sant Pau, Barcelona, Catalu?a, 08041, Spain|Hospital Universitario Insular de Gran canaria, Las Palmas De Gran Canaria, Gran Canaria, 35016, Spain|Hospital Son Espases, Palma De Mallorca, Illes Balears, 07120, Spain|Hospital Universitario de Cruces, Baracaldo, Vizcaya, 48903, Spain|Complejo Hospitalario de A Coru?a, A Coru?a, 15006, Spain|Hospital General de Alicante, Alicante, 03010, Spain|Hospital Vall Hebron, Barcelona, 08035, Spain|Hospital Universitario Fundación Jiménez Díaz, Madrid, 28040, Spain|Hospital Puerta de Hierro, Madrid, 28222, Spain|Hospital Clínico de Salamanca, Salamanca, 37007, Spain|Hospital Universitari i Politécnic La Fe, Valencia, 46009, Spain|Hospital General de Valencia, Valencia, 46014, Spain Less <<
NCT05361564 Non-small Cell Lung Cancer PHASE2 UNKNOWN 2025-06-24 Yonsei University Health Syste... More >>m, Severance Hospital, Seoul, Korea, Republic of Less <<
NCT01449461 Lymphoma, Large-Cell, Anaplast... More >>ic|Carcinoma, Non-Small-Cell Lung Less << PHASE1|PHASE2 COMPLETED 2020-02-18 -
NCT03719898 Anaplastic Large Cell Lymphoma... More >>, ALK-Positive Less << PHASE2 WITHDRAWN 2020-06-16 Fox Chase Cancer Center, Phila... More >>delphia, Pennsylvania, 19011, United States Less <<
NCT03535740 ALK-positive Advanced NSCLC PHASE2 COMPLETED 2024-08-21 University of California Irvin... More >>e Health Chao Family Comprehensive Cancer Center, Orange, California, 92868, United States|The Oncology Institute of Hope and Innovation, Whittier, California, 90602, United States|USOR - Rocky Mountain Cancer Centers - Pueblo, Pueblo, Colorado, 81008, United States|Florida Hospital Medical Group, Orlando, Florida, 32804, United States|Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, 48201, United States|Washington University School of Medicine, Saint Louis, Missouri, 63110, United States|Levine Cancer Institute - Southpark, Charlotte, North Carolina, 28211, United States|Providence Portland Medical Center, Portland, Oregon, 97213, United States|Sarah Cannon Research Institute, Nashville, Tennessee, 37203, United States|USOR - Virginia Cancer Specialists - Fairfax Office, Fairfax, Virginia, 22031, United States|Saint Vincent's Hospital Melbourne, Fitzroy, Victoria, 3065, Australia|Peninsula & South Eastern Haematology and Oncology Group, Frankston, Victoria, 3199, Australia|Sir Charles Gairdner Hospital, Nedlands, Western Australia, 6009, Australia|Klinikum Klagenfurt Am Worthersee, Klagenfurt, Carinthia, 9020, Austria|Krankenhaus Elisabethinen Linz, Linz, Upper Austria, 4020, Austria|Cross Cancer Institute, Edmonton, Alberta, T6G 1Z2, Canada|Tom Baker Cancer Center, Calgary, British Columbia, T2N 2T9, Canada|Toronto University Health Network, Toronto, Ontario, M5G 2M9, Canada|McGill University Health Centre, Montreal, Quebec, H4A 3J1, Canada|Beijing Cancer Hospital, Beijing, Beijing, 100000, China|The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510000, China|Jilin Provincial Cancer Hospital (Changchun Cancer Hospital), Changchun, Jilin, 130000, China|Shanghai Pulmonary Hospital, Shanghai, Shanghai, 200001, China|The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, China|Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310000, China|Hopital Haut-Leveque, Pessac, Aquitaine, 33604, France|Centre Hospitalier Intercommunal de Creteil, Creteil, Ile-de-france, 94010, France|Hopital Larrey, CHU de Toulouse, Service de Pneumologie, Toulouse Cedex 9, Midi-pyrenees, 31059, France|Assistance Publique-Hopitaux de Marseille Hopital Nord, Marseille, Provence Alpes COTE D'azur, 13915, France|Centre de Lutte Contre le Cancer Centre Leon Berard, Lyon, Rhone-alpes, 69008, France|Thoraxklinik Heidelberg gGmbH, Heidelberg, Baden-wuerttemberg, 69126, Germany|Universitatsklinikum Ulm, Ulm, Baden-wuerttemberg, 89081, Germany|Klinikum Kempten-Oberallgau, Kempten, Bavaria, 87439, Germany|Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, 80336, Germany|Pius Hospital Oldenburg, Oldenburg, Niedersachsen, 26121, Germany|Evangelisches Krankenhaus Hamm, Hamm, Nordrhein-westfalen, 59063, Germany|HELIOS Klinikum Emil von Behring, Berlin, 14165, Germany|Prince of Wales Hospital, Shatin, New Territories, Hong Kong|Queen Mary Hospital, Hong Kong, 00852, Hong Kong|Queen Mary Hospital, Hong Kong, Hong Kong|Queen Elizabeth Hospital, Kowloon, 1076, Hong Kong|Princess Margaret Hospital - Hong Kong, Kowloon, Hong Kong|Azienda Ospedaliera San Camillo Forlanini, Roma, Lazio, 00152, Italy|Centro di Riferimento Oncologico di Aviano, Aviano, Pordenone, 33081, Italy|Azienda Ospedaliero - Universitaria San Luigi Gonzaga, Orbassano, Torino, 10043, Italy|Istituto Europeo di Oncologia, Milano, 20141, Italy|Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, 80131, Italy|Azienda Ospedaliero Universitaria di Parma, Parma, 43126, Italy|Azienda USL della Romagna, Ravenna, 48121, Italy|Fujita Health University Hospital, Toyoake, Aichi, 470-1192, Japan|Kanagawa Cancer Center, Yokohama, Kanagawa, 241-8515, Japan|Sendai Kousei Hospital, Sendai, Miyagi, 980-0873, Japan|Okayama University Hospital, Okayama-city, Okayama, 700-8558, Japan|Kansai Medical University Hirakata Hospital, Hirakata-shi, Osaka, 573-1191, Japan|The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, 135-8550, Japan|National Cancer Center, Goyang-si, Gyeonggi-do, 411-769, Korea, Republic of|Gachon University Gil Medical Center, Incheon, Gyeonggi-do, 21565, Korea, Republic of|Korea University Anam Hospital, Seoul, Gyeonggi-do, 02841, Korea, Republic of|Chungbuk National University Hospital, Cheongju-si, Gyeongsangbuk-do, 28644, Korea, Republic of|Keimyung University Dongsan Medical Center, Daegu, 41931, Korea, Republic of|Seoul National University Hospital, Seoul, 03080, Korea, Republic of|Severance Hospital, Seoul, 03722, Korea, Republic of|Asan Medical Center, Seoul, 05505, Korea, Republic of|Samsung Medical Center, Seoul, 135-710, Korea, Republic of|Maastricht University Medical Centre, Maastricht, Limburg, 6229 HX, Netherlands|Vrije Universiteit Medisch Centrum, Amsterdam, Noord-holland, 1081 HV, Netherlands|Erasmus University Medical Center, Rotterdam, Zuid-holland, 3015 CE, Netherlands|Institut Catala d'Oncologia Badalona - Hospital Germans Trias i Pujol, Badalona, Barcelona, 08916, Spain|Complejo Hospitalario Universitario A Coruna, A Coruna, LA Coruna, 15006, Spain|Hospital Universitario Vall d'Hebron, Barcelona, 08035, Spain|Hospital Universitario Ramon Y Cajal, Madrid, 28034, Spain|Hospital Universitario La Paz, Madrid, 28046, Spain|Hospital Universitario Puerta de Hierro - Majadahonda, Madrid, 28222, Spain|Skanes Universitetssjukhus i Lund, Lund, Skane, 214 01, Sweden|Karolinska Universitetssjukhuset, Stockholm, 171 76, Sweden|Uppsala Akademiska Sjukhus, Uppsala, 751 85, Sweden|Changhua Christian Hospital, Changhua City, Changhwa, 500, Taiwan|National Cheng Kung University, Tainan, Tainan CITY, 70403, Taiwan|China Medical University Hospital, Taichung, 404, Taiwan|Taichung Veterans General Hospital, Taichung, 40705, Taiwan Less <<
NCT02784158 Non-small Cell Lung Cancer|Lun... More >>g Cancer|Advanced Malignancies|Carcinoma Less << NO_LONGER_AVAILABLE - UC San Diego Moores Cancer Cen... More >>ter (Site 099), La Jolla, California, 92093-0698, United States|UCI Medical Center-Chao Family Comprehensive (Site 210), Orange, California, 92868-3201, United States|Karmanos Cancer Institute (Site 070), Detroit, Michigan, 48201, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.71mL

0.34mL

0.17mL

8.56mL

1.71mL

0.86mL

17.12mL

3.42mL

1.71mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Zhang S, Anjum R, et al. The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models. Clin Cancer Res. 2016 Nov 15;22(22):5527-5538.

[2]Huang WS, Liu S, et al. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. J Med Chem. 2016 May 26;59(10):4948-64.

[3]Ali R, Arshad J, et al. Brigatinib for ALK-positive metastatic non-small-cell lung cancer: design, development and place in therapy. Drug Des Devel Ther. 2019 Feb 8;13:569-580.

[4]Uchibori K, Inase N, et al. Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer. Nat Commun. 2017 Mar 13;8:14768.

[5]Wen J, Bao S, et al. A reliable and stable method for determination of brigatinib in rat plasma by UPLC-MS/MS: Application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Nov 15;1068-1069:84-89.

[6] Katayama R. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40. doi: 10.1073/pnas.1019559108. Epub 2011 Apr 18.

[7] Siaw JT. Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice. Oncotarget. 2016 May 17;7(20):29011-22. doi: 10.18632/oncotarget.8508.

[8] Huang WS. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. J Med Chem. 2016 May 26;59(10):4948-64. doi: 10.1021/acs.jmedchem.6b00306. Epub 2016 May 12.

[9] Descourt R. Brigatinib in patients with ALK-positive advanced non-small-cell lung cancer pretreated with sequential ALK inhibitors: A multicentric real-world study (BRIGALK study). Lung Cancer. 2019 Oct;136:109-114. doi: 10.1016/j.lungcan.2019.08.010. Epub 2019 Aug 14.

[10] NCI Drug Dictionary

 

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