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Chemical Structure| 1108743-60-7 Chemical Structure| 1108743-60-7

Structure of Entrectinib
CAS No.: 1108743-60-7

Chemical Structure| 1108743-60-7

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Entrectinib (NMS-E628) is an orally active, BBB-penetrant inhibitor of TrkA/B/C, ROS1, and ALK, with IC50 values of 1, 3, 5, 12, and 7 nM, respectively. It induces apoptosis and cell cycle arrest in cancer cells, exhibits antitumor activity, and attenuates bleomycin-induced lung fibrosis in mice.

Synonyms: NMS-E628; RXDX-101

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Product Details of Entrectinib

CAS No. :1108743-60-7
Formula : C31H34F2N6O2
M.W : 560.64
SMILES Code : O=C(NC1=NNC2=C1C=C(CC3=CC(F)=CC(F)=C3)C=C2)C4=CC=C(N5CCN(C)CC5)C=C4NC6CCOCC6
Synonyms :
NMS-E628; RXDX-101
MDL No. :MFCD28129099
InChI Key :HAYYBYPASCDWEQ-UHFFFAOYSA-N
Pubchem ID :25141092

Safety of Entrectinib

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

Related Pathways of Entrectinib

RTK

Isoform Comparison

Biological Activity

Target
  • ALK

In Vitro:

Cell Line
Concentration Treated Time Description References
LLC-PK1 cells 1 µM 3.5 hours To evaluate the interaction of Entrectinib with P-gp, results showed that Entrectinib had a lower AP-ER value (1.1-1.15), indicating a weaker interaction with P-gp. PMC7283026
KM12 cells <30 nM 72 hours To evaluate the inhibitory effect of gilteritinib on KM12 cells, the results showed that KM12 cells were highly sensitive to gilteritinib. PMC7904790
Ba/F3 cells 12.7 nM 72 hours To evaluate the inhibitory effect of gilteritinib on TPM3-NTRK1 G667C mutant Ba/F3 cells, the results showed that the mutant cells were more sensitive to gilteritinib. PMC7904790
mouse primary bone marrow-derived macrophages (BMDMs) 0.88 µM 4 hours inhibited MSU-induced IL-1β production PMC10772347
human THP-1 cells 2 µM 1 hour inhibited nigericin-induced IL-1β secretion and caspase-1 cleavage PMC10772347
SY5Y-TrkB cells 1 nM to 200 nM 1 hour Entrectinib significantly inhibited TrkB phosphorylation, with substantial inhibition observed at 1 nM concentration, and almost complete inhibition at 10 nM or higher concentrations. PMC4792275
NLF-TrkB cells 50 nM 1 hour Entrectinib almost completely inhibited TrkB phosphorylation in NLF-TrkB cells at 50 nM concentration. PMC4792275
IMPE cells 1 nM to 100 nM 24 hours To evaluate the effect of Entrectinib on BIM expression in IMPE cells, results showed increased BIM expression PMC7478141
IMPE cells 10 nM 0 to 24 hours To evaluate the effect of Entrectinib on BIM expression and RAF>MEK>ERK signaling in IMPE cells, results showed increased BIM expression and reactivation of RAF>MEK>ERK signaling PMC7478141
IMPE cells 10 nM to 1 μM 24 hours To evaluate the effect of BIM deletion on the sensitivity of IMPE cells to Entrectinib, results showed that BIM deletion reduced cell sensitivity to Entrectinib PMC7478141
Ba/F3 cells 50 nM 72 hours To evaluate the effect of Alectinib on ALK-TKI resistant mutations PMC7904790
IMPE cells 250 nM 2 or 24 hours To evaluate the effect of Cobimetinib on the RAF>MEK>ERK signaling pathway in IMPE cells, results showed that Cobimetinib alone effectively inhibited pERK at 2 h, but reactivation of pERK was detected at 24 h. PMC7478141
MLE-12 cells 250 nM 2 or 24 hours To evaluate the effect of Cobimetinib on the RAF>MEK>ERK signaling pathway in MLE-12 cells, results showed that Cobimetinib alone effectively inhibited pERK at 2 h, but reactivation of pERK was detected at 24 h. PMC7478141

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rats Brain distribution model Intravenous injection 100 mg/kg or 200 mg/kg Once daily for 3 weeks followed by 1 week off To evaluate the brain distribution of Entrectinib in rats, results showed that Entrectinib did not reach steady state within 6 hours, but its CSF/unbound plasma concentration ratio (CSF/Cu,p) was more favorable than that of crizotinib and larotrectinib. PMC7283026
mice BALB/c nu/nu mice oral 150 mg/kg Single dose, lasting for 3 days To evaluate the inhibitory effect of gilteritinib on KM12 cell xenografts, the results showed that gilteritinib significantly inhibited tumor growth. PMC7904790
mice LPS-induced systemic inflammation model intraperitoneal injection Single bolus followed by continuous infusion for 6 hours significantly improved the survival rate of mice and inhibited the production of IL-1β in serum PMC10772347
nude mice SY5Y-TrkB xenograft model oral 30 mg/kg once daily for 5 days/week Entrectinib significantly inhibited the growth of SY5Y-TrkB xenograft tumors and significantly prolonged event-free survival (EFS). PMC4792275
Nude mice HER2-positive breast cancer xenograft model Oral 10 mg/kg single injection, lasted for 6 hours The combination of Entrectinib and Pacritinib significantly suppressed tumor growth and induced apoptosis in HER2-positive breast cancer xenografts. PMC11533721
mice NOD-SCID mice oral 60 mg/kg twice daily, 7 days/week To evaluate the effect of Entrectinib on IMPE cell-derived tumors, results showed that BIM deletion reduced tumor sensitivity to Entrectinib PMC7478141
mice BALB/c nu/nu mice oral 15 mg/kg twice per week To evaluate the therapeutic effect of Alectinib on EML4-ALK I1171N +F1174I mutant tumors PMC7904790
mice BALB/c nu/nu mice oral 10 mg/kg Once daily for 4 weeks To evaluate the in vivo antitumor effect of Gilteritinib on EML4-ALK I1171N +F1174I mutant tumors, results showed that Gilteritinib significantly reduced tumor volume. PMC7904790
mice NOD-SCID mice oral 0.5 mg/g Every 12 hours for 48 hours To evaluate the effect of Cobimetinib in combination with Entrectinib on IMPE cell-derived tumors, results showed that the combination significantly delayed the onset of drug resistance. PMC7478141
Female severe combined immunodeficient beige mice (BALB/cAjcl-nu/nu) KM12-ER xenograft model Oral 15 mg/kg Once daily for 14 days Evaluate the inhibitory effect of simvastatin combined with entrectinib on resistant tumor growth PMC11194613

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT05770544 Solid Tumor|Haematological Mal... More >>ignancy|Malignancy|Malignant Neoplasm|Lymphoproliferative Disorders|Neoplasms by Histologic Type|Neoplasms by Site|Cancer|Brain Neoplasms|Melanoma|Glioma Less << PHASE2|PHASE3 RECRUITING 2025-10-29 Belfast City Hospital, Belfast... More >>, BT9 7AB, United Kingdom|University Hospital Birmingham, Birmingham, B15 2TT, United Kingdom|Birmingham Children's Hospital, Birmingham, United Kingdom|Bristol Royal Hospital for Children, Bristol, BS2 8BJ, United Kingdom|Bristol Haematology and Oncology Centre, Bristol, BS2 8ED, United Kingdom|Addenbrooke's Hospital, Cambridge, CB2 OQQ, United Kingdom|Velindre Cancer Centre, Cardiff, CF14 2TL, United Kingdom|Western General Hospital, Edinburgh, EH4 2XU, United Kingdom|The Beatson Hospital, Glasgow, G12 OYN, United Kingdom|Royal Hospital for Children Glasgow, Glasgow, G51 4TF, United Kingdom|Leeds General Infirmary, Leeds, LS1 3EX, United Kingdom|Leicester Royal Infirmary, Leicester, LE1 5WW, United Kingdom|Alder Hey Hospital, Liverpool, L14 5AB, United Kingdom|The Royal Marsden Hospital, London Borough of Sutton, SM2 5PT, United Kingdom|University College London Hospital, London, NW1 2BU, United Kingdom|Guy's Hospital, London, SE1 9RT, United Kingdom|Great Ormond Street Hospital, London, WC1N 3JH, United Kingdom|Royal Manchester Children's Hospital, Manchester, M13 9WL, United Kingdom|The Christie Hospital, Manchester, M20 4BX, United Kingdom|Great North Children's Hospital, Newcastle, NE1 4LP, United Kingdom|Freeman Hospital, Newcastle, NE7 7DN, United Kingdom|Churchill Hospital, Oxford, OX3 7LE, United Kingdom|John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom|Weston Park Hospital, Sheffield, S10 2SJ, United Kingdom|Southampton General Hospital, Southampton, SO16 6YD, United Kingdom|Clatterbridge Cancer Centre, Wirral, CH63 4JY, United Kingdom Less <<
NCT03066661 Cancers With NTRK, ROS1, or AL... More >>K Gene Fusions Less << NO_LONGER_AVAILABLE - 1-844-Startrk (782-7875), San ... More >>Diego, California, 92121, United States Less <<
NCT02650401 Solid Tumors|CNS Tumors PHASE1|PHASE2 ACTIVE_NOT_RECRUITING 2025-06-15 Rady Childrens Hospital, San D... More >>iego, California, 92123, United States|UCSF Benioff Children's Hospital, San Francisco, California, 94158, United States|Children's Hospital Colorado, Aurora, Colorado, 80045, United States|Egleston Children's Hospital at Emory University Atlanta, Atlanta, Georgia, 30322, United States|University of Chicago, Chicago, Illinois, 60637, United States|Johns Hopkins University, Baltimore, Maryland, 21205, United States|Dana Farber Cancer Institute, Boston, Massachusetts, 02215, United States|Washington University,St. Louis Children's Hospital, Saint Louis, Missouri, 63110, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Nationwide Children's Hospital, Columbus, Ohio, 43205, United States|Oregon Health & Science Uni, Portland, Oregon, 97239, United States|Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, United States|St. Jude Children'S Research Hospital, Memphis, Tennessee, 38105, United States|Texas Children's Cancer and Hematology Center, Houston, Texas, 77030, United States|Primary Children's Hospital, Salt Lake City, Utah, 84113, United States|The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada|Beijing Children's Hospital, Capital Medical University, Beijing, DUMMY_VALUE, China|Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China|Centre Leon Berard, Lyon, 69373, France|H?pital de la Timone, Oncologie Pédiatrique, Marseille, 13385, France|Universitaetsklinikum Heidelberg, Heidelberg, Baden Wuerttemberg, 69120, Germany|Hong Kong Children's Hospital, Hong Kong, 00000, Hong Kong|Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, 20133, Italy|Hospital Infantil Universitario Nino Jesus, Madrid, 28009, Spain|Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, United Kingdom|Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, United Kingdom Less <<
NCT06694129 Non-Small Cell Lung Cancer|ROS... More >>1 Gene Rearrangement|Resistance|Targeted Therapy Less << NOT_YET_RECRUITING 2027-12-01 -
NCT02568267 Breast Cancer|Cholangiocarcino... More >>ma|Colorectal Cancer|Head and Neck Neoplasms|Lymphoma, Large-Cell, Anaplastic|Melanoma|Neuroendocrine Tumors|Non-Small Cell Lung Cancer|Ovarian Cancer|Pancreatic Cancer|Papillary Thyroid Cancer|Primary Brain Tumors|Renal Cell Carcinoma|Sarcomas|Salivary Gland Cancers|Adult Solid Tumor Less << PHASE2 ACTIVE_NOT_RECRUITING 2025-12-31 Dignity Health St Joseph's Hos... More >>pital and Medical Center, Phoenix, Arizona, 85013, United States|Mayo Clinic, Phoenix, Arizona, 85054, United States|City of Hope Cancer Center, Duarte, California, 91010, United States|Scripps Clinic, La Jolla, California, 92037, United States|University of California San Diego Moores Cancer Center, La Jolla, California, 92093, United States|Southern California Kaiser Permanente, Los Angeles, California, 90027, United States|University of Southern California Medical Center, Los Angeles, California, 90032, United States|Univ Of California Irvine College Of Medicine, Orange, California, 92868, United States|UCSF Mount Zion Medical Ctr, San Francisco, California, 94115, United States|Sarcoma Oncology Center, Santa Monica, California, 90403, United States|University of Colorado Cancer Center, Aurora, Colorado, 80045, United States|Yale University, New Haven, Connecticut, 6519, United States|Georgetown University Medical Center Lombardi Cancer Center, Washington, District of Columbia, 20007, United States|Florida Cancer Specialists - Sarasota, Sarasota, Florida, 34232, United States|H. Lee Moffitt Cancer Center and Research Inst., Tampa, Florida, 33612-9497, United States|University Cancer & Blood Center, LLC, Athens, Georgia, 30607, United States|Winship Cancer Institute, Atlanta, Georgia, 30322, United States|Southeastern Regional Medical Center, Inc., Newnan, Georgia, 30265, United States|Northwestern University, Chicago, Illinois, 60611, United States|Advocate Medical Group - Park Ridge, Luther Lane - Oncology, Park Ridge, Illinois, 60068, United States|Midwestern Regional Medical Center, Zion, Illinois, 60099, United States|Weinberg Cancer Institution at Franklin Square, Baltimore, Maryland, 21237, United States|Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States|Dana Farber Cancer Institute, Boston, Massachusetts, 02215, United States|University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, 48109, United States|Karmanos Cancer Center, Detroit, Michigan, 48201, United States|Henry Ford Hospital, Detroit, Michigan, 48202, United States|Regents of the University of Minnesota, Minneapolis, Minnesota, 55455, United States|Washington University, Saint Louis, Missouri, 63128, United States|Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley, Las Vegas, Nevada, 89169, United States|North Shore Hem Onc Associates, East Setauket, New York, 11733, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10022, United States|Levine Cancer Institute, Charlotte, North Carolina, 28204, United States|Duke Cancer Institute, Durham, North Carolina, 27710, United States|OSU, James Cancer Hospital, Columbus, Ohio, 43210, United States|Cancer Treatment Centers of America, Tulsa, Oklahoma, 74133, United States|Oregon Health & Science Univ, Portland, Oregon, 97239, United States|Mary Crowley Medical Research Center, Dallas, Texas, 75230, United States|University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States|Baylor Scott & White Health, Temple, Texas, 76508, United States|University of Utah Hospitals & Clinics, Salt Lake City, Utah, 84112, United States|Virginia Cancer Specialists, PC, Fairfax, Virginia, 22031, United States|Virginia Oncology Associates - Hampton, Norfolk, Virginia, 23502, United States|University of Washington Seattle Cancer Care Alliance, Seattle, Washington, 98109, United States|Liverpool Hospital, Liverpool, New South Wales, 2170, Australia|Newcastle Private Hospital, Newcastle, New South Wales, 2305, Australia|Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia|Austin Health, Heidelberg, Victoria, 3084, Australia|Antwerp University Hospital, Edegem, 2650, Belgium|Beijing Cancer Hospital, Beijing, 100142, China|Sichuan Provincial Cancer Hospital, Chengdu, 610041, China|Cancer Center of Guangzhou Medical University, Guangzhou, 510000, China|Zhejiang Cancer Hospital, Hangzhou, 310022, China|Harbin Medical University Cancer Hospital, Harbin, 150081, China|Shanghai chest hospital, Shanghai, 200030, China|Fudan University Shanghai Cancer Center, Shanghai, 200120, China|Shenzhen People's Hospital, Shenzhen, 510852, China|Tianjin Cancer Hospital, Tianjin, 300060, China|Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan City, 430023, China|Institut de Cancerologie de l Ouest, Angers, 49055, France|Institut Bergonie, Bordeaux, 33076, France|Centre Leon Berard, Lyon, 69373, France|H?pital Nord - AP-HM Marseille#, Marseille cedex 20, 13915, France|H?pital de la Timone, Marseille cedex 5, 13385, France|Institut de Recherche en Cancérologie de Montpellier, Montpellier, 34090, France|Institut Curie, Paris, 75005, France|Institut De Cancerologie De L'ouest - Rene Gauducheau - Biology, Saint Herblain, 44805, France|Institut Claudius Regaud, Toulouse, 31059, France|Institut Gustave Roussy, Villejuif cedex, 94805, France|Evang. Lungenklinik Berlin Klinik für Pneumologie, Berlin, 13125, Germany|Universitaetsklinikum Carl Gustav Carus TU Dresden, Dresden, 01307, Germany|Universitaetsmedizin Goettingen, G?ttingen, 37075, Germany|NCT Uniklinikum Heidelberg, Heidelberg, 69120, Germany|Universitaetsklinikum Koeln, K?ln, 50937, Germany|Princess Margaret Hospital, Hong Kong, Hong Kong|The University of Hong Kong, Hong Kong, Hong Kong|Queen Elizabeth Hospital, Kowloon, DUMMY_VALUE, Hong Kong|The Chinese University of Hong Kong, Shatin, 123456, Hong Kong|Seconda Università degli Studi di Napoli, Napoli, Campania, 80131, Italy|Università Campus Bio-Medico di Roma, Roma, Lazio, 128, Italy|Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Lombardia, 20133, Italy|Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda), Milano, Lombardia, 20162, Italy|Azienda Ospedaliero Universitaria Pisana, Pisa, Toscana, 56126, Italy|Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia, Perugia, Umbria, 6132, Italy|IOV - Istituto Oncologico Veneto - IRCCS, Padova, Veneto, 35128, Italy|Aichi Cancer Center Hospital, Aichi, 464-8681, Japan|National Cancer Center Hospital, Chuo, 104-0045, Japan|NHO Kyushu Cancer Center, Fukuoka, 811-1395, Japan|Hyogo Cancer Center, Dept of Respiratory Medicine, Hyogo, 673-8558, Japan|National Cancer Center Hospital, Kashiwa-shi, 277-8577, Japan|NHO Shikoku Cancer Center, Matsuyama-shi, 791-0280, Japan|Miyagi Cancer Center, Miyagi, 981-1293, Japan|Niigata Cancer Center Hospital, Niigata, 951-8566, Japan|Osaka City General Hospital, Osaka, 534-0021, Japan|Kindai University Hospital, Osaka, 589-8511, Japan|Shizuoka Cancer Center, Shizuoka, 411-8777, Japan|Seoul National University Hospital, Seoul, 03080, Korea, Republic of|Asan Medical Center., Seoul, 05505, Korea, Republic of|Samsung Medical Center, Seoul, 06351, Korea, Republic of|Severance Hospital, Yonsei University Health System, Seoul, 120-752, Korea, Republic of|NKI The Netherlands Cancer Institute, Amsterdam, 1066 CX, Netherlands|Leids Universitair Medisch Centrum, Leiden, 2333 ZA, Netherlands|Uniwersyteckie Centrum Kliniczne, Gdansk, 80-214, Poland|Centrum Onkologii-Instytut im.M.Sklodowskiej Curie, Gliwice, 44-101, Poland|Szpital Kliniczny Przemienienia Panskiego Uni. Medycznego im. Karola Marcinkowskiego, Pozna?, 60-569, Poland|Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego, Warszawa, 02-781, Poland|National University Hospital, Singapore, 119228, Singapore|National Cancer Centre, Singapore, 169610, Singapore|Centro Nacional de Investigaciones Oncológicas(CNIO), Fuenlabrada, Madrid, 28942, Spain|Vall d?Hebron Institute of Oncology (VHIO), Barcelona, Barcelona, 08035, Spain|Hospital Universitario Ramon y Cajal, Madrid, 28034, Spain|Hospital Universitario Clínico San Carlos, Madrid, 28040, Spain|Hospital Universitario 12 de Octubre, Madrid, 28041, Spain|Hospital Universitario La Paz, Madrid, 28046, Spain|Hospital Clinico Universitario Virgen de la Victoria, Malaga, 29010, Spain|Hospital Universitario Virgen del Rocio, Sevilla, 41013, Spain|National Cheng Kung University Hospital, Tainan, 70457, Taiwan|National Taiwan University Hospital, Taipei, 00100, Taiwan|Taipei Veterans General Hospital, Taipei, 11217, Taiwan|Addenbrookes Hospital, Cambridge, CB2 0QQ, United Kingdom|Sarah Cannon Research Institute, London, W1G 6AD, United Kingdom|The Christie, Manchester, M20 4BX, United Kingdom Less <<
NCT02097810 Locally Advanced Solid Tumors|... More >>Metastatic Solid Tumors Less << PHASE1 COMPLETED 2020-06-02 UC Irvine Medical Center, Oran... More >>ge, California, 92868, United States|University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California, 94158, United States|University Of Colorado, Aurora, Colorado, 80045, United States|Georgetown University Medical Center, Washington, District of Columbia, 20007, United States|Florida Cancer Specialists - Sarasota, Sarasota, Florida, 34232, United States|Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Tennessee Oncology, Nashville, Tennessee, 37203, United States|University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, United States|Samsung Medical Center, Seoul, 06531, Korea, Republic of Less <<

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Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.78mL

0.36mL

0.18mL

8.92mL

1.78mL

0.89mL

17.84mL

3.57mL

1.78mL

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