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Chemical Structure| 1032900-25-6 Chemical Structure| 1032900-25-6

Structure of Ceritinib
CAS No.: 1032900-25-6

Chemical Structure| 1032900-25-6

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Ceritinib (LDK378) is a selective, orally bioavailable, and ATP-competitive ALK tyrosine kinase inhibitor with an IC50 of 200 pM. Ceritinib (LDK378) also inhibits IGF-1R, InsR, and STK22D with IC50 values of 8, 7, and 23 nM, respectively. Ceritinib (LDK378) exhibits potent antitumor activity.

Synonyms: LDK378

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Product Citations

Product Citations

Zhengbo Song ; Shifeng Lian ; Silvia Mak ; Maggie Zi-Ying Chow ; Chunwei Xu ; Wenxian Wang , et al.

Abstract: Introduction: Gene fusion variants in ALK-rearranged NSCLC may predict patient outcomes, but previous results have been inconclusive. Fusion isoforms coexisting in the same tumor may affect the efficacy of targeted therapy, but they have not been investigated. Methods: Patients with ALK-rearranged NSCLC who received crizotinib treatments were recruited. Precrizotinib tumor tissues were analyzed by the anchored multiplex polymerase chain reaction for targeted RNA sequencing. Kaplan-Meier and Cox regression were used to compare overall and progression-free survivals. Results: Of the 51 studied subjects, EML4-ALK variant types v1, v2, v3, and others were detected in 23 (45.1%), five (9.8%), 19 (37.3%), and four patients (7.8%), respectively. Multiple EML4-ALK RNA isoforms were detected in 24 tumors (47.1%), and single isoform in 27 (52.9%). Most of the v3 tumors (16 of 19) harbored both v3a and v3b RNA isoforms. Multiple isoforms were also detected in eight non-v3 tumors (33.3% of all 24 multiple isoforms; five v1, two v5′, and one v2). Compared with patients with single isoform, those with multiple isoforms had worse progression-free (hazard ratio and 95% confidence interval: 2.45 [1.06–5.69]) and overall (hazard ratio [95% confidence interval]: 3.74 [1.26–11.13]) survivals after adjusting for potential confounders including variant type. Using the patient-derived H2228 cells known to express v3a and v3b, our single-cell polymerase chain reaction detected either v3a or v3b in most single cells. Treatment of H2228 cells by three ALK inhibitors revealed increased ratios of v3a-to-v3b expression over time. Conclusions: Intratumoral EML4-ALK isoforms may predict the efficacy of targeted therapy in ALK-rearranged NSCLC. Temporal changes of intratumoral fusion isoforms may result from differential selection pressures that a drug might have on one isoform over another. Larger studies on fusion heterogeneity using RNA sequencing are warranted.

Keywords: RNA sequencing ; ALK fusion heterogeneity ; Fusion isoforms ; Crizotinib ; ALK TKI

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Product Details of Ceritinib

CAS No. :1032900-25-6
Formula : C28H36ClN5O3S
M.W : 558.14
SMILES Code : O=S(C1=CC=CC=C1NC2=NC(NC3=CC(C)=C(C4CCNCC4)C=C3OC(C)C)=NC=C2Cl)(C(C)C)=O
Synonyms :
LDK378
MDL No. :MFCD26142648
InChI Key :VERWOWGGCGHDQE-UHFFFAOYSA-N
Pubchem ID :57379345

Safety of Ceritinib

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H360
Precautionary Statements:P201-P202-P281-P308+P313-P405-P501

Related Pathways of Ceritinib

RTK

Isoform Comparison

Biological Activity

Target
  • ALK

    ALK, IC50:0.2 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
A375X1 cells 100 nM 72 h To evaluate the effect of Ceritinib on the growth of A375X1 cells, results showed that Ceritinib combined with BRAF inhibitor significantly suppressed cell proliferation. PMC6172729
BRAF/NRAS-WT melanoma cell lines 0.5 or 2.5μM 72 h Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both 3D spheroid culture and long-term colony formation experiments. PMC5752595
OVCAR-8 0.75 μM 8-10 days Ceritinib synergized with the PARPi olaparib in HR-proficient OVCAR-8 cells, inducing tumor cell death PMC8770599
COV362 0.75 μM 8-10 days Ceritinib synergized with the PARPi olaparib in BRCA1-mutant COV362 cells, inducing tumor cell death PMC8770599
PC3 0.75 μM 8-10 days Ceritinib synergized with the PARPi olaparib in prostate cancer PC3 cells, inducing tumor cell death PMC8770599
MDA-MB-231 0.75 μM 8-10 days Ceritinib did not synergize with the PARPi olaparib in breast cancer MDA-MB-231 cells PMC8770599
OVCAR-8 0.75 μM 8-10 days Ceritinib synergized with the PARPi olaparib in HR-proficient OVCAR-8 cells, inhibiting cell proliferation. PMC8770599
COV362 0.75 μM 8-10 days Ceritinib synergized with the PARPi olaparib in BRCA1-mutant COV362 cells, inhibiting cell proliferation. PMC8770599
Ba/F3 cells 300, 600, 1000 nM 2-4 weeks Identify ceritinib- or lorlatinib-resistant ALK-compound mutations through ENU mutagenesis screening and evaluate their sensitivity to ALK-TKIs. PMC6441848
Ba/F3 cells 300 nM 3 h Assess the effect of ALK-TKIs on ALK phosphorylation and downstream signaling in Ba/F3 cells, confirming resistance of ALK-G1202R + G1269A double mutation to lorlatinib. PMC6441848
NCI-H3122 cells 200 nM 2-4 months To study the evolution of resistance to Ceritinib in NCI-H3122 cells, results showed that cells were able to grow at 200 nM Ceritinib concentration, and resistance gradually increased. PMC7224215
H3122 cells 1 µM 6 months Establishing a Ceritinib-resistant cell model to analyze DNA methylation and transcriptome changes PMC9440127
NB-1 1.5 nM to 10 μM 6 days To evaluate the anti-proliferative and cytotoxic effects of Ceritinib on NB-1 cells, the results showed that Ceritinib significantly inhibited the proliferation of NB-1 cells. PMC5435462
SH-SY5Y 1.5 nM to 10 μM 6 days To evaluate the anti-proliferative effects of Ceritinib on SH-SY5Y cells, the results showed that Ceritinib reduced the anti-proliferative activity in SH-SY5Y cells. PMC5435462
NB-1643 1.5 nM to 10 μM 6 days To evaluate the anti-proliferative effects of Ceritinib on NB-1643 cells, the results showed that Ceritinib reduced the anti-proliferative activity in NB-1643 cells. PMC5435462
IMR-32 1.5 nM to 10 μM 6 days To evaluate the anti-proliferative effects of Ceritinib on IMR-32 cells, the results showed that Ceritinib reduced the anti-proliferative activity in IMR-32 cells. PMC5435462

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD/SCID gamma mice A375X1-induced melanoma model oral 50 mg/kg once daily for 7 consecutive days To evaluate the effect of Ceritinib combined with BRAF inhibitor on tumor growth, results showed that the combination treatment significantly inhibited tumor growth. PMC6172729
NSG mice BRAF/NRAS-WT melanoma xenograft model Oral 25mg/kg Daily dosing for 24 days The combination of ceritinib and trametinib significantly inhibited tumor growth, showing more pronounced effects compared to trametinib or ceritinib monotherapy. PMC5752595
SCID beige mice HGSOC patient-derived xenograft (PDX) models oral gavage 100 mg/kg daily for up to 9 weeks The combination of ceritinib and olaparib induced tumor regression more effectively than olaparib alone in HGSOC PDX models, particularly in models with preexisting PARPi sensitivity. PMC8770599
BALB-c nu/nu mice JFCR-041-2 cell xenograft model oral 10, 30, 50 mg/kg once daily for 5-6 days/week Evaluate the antitumor effect of lorlatinib in the JFCR-041-2 cell xenograft model, finding tumor recurrence after lorlatinib treatment and identifying the ALK-G1202R + G1269A double mutation. PMC6441848
CB17 SCID mice SH-SY5Y and NB-1691 xenograft models Oral 50 mg/kg Once daily for 49 days To evaluate the anti-tumor efficacy of combination therapy with Ceritinib and Ribociclib in neuroblastoma xenograft models, results showed that combination therapy significantly prolonged event-free survival and achieved complete and sustained tumor regressions. PMC5457336
BALB/c nude mice LR cell xenograft model Intraperitoneal injection 100 mg/kg Every 24 hours for 13 days Evaluate the inhibitory effect of 5fdC on Ceritinib-resistant tumors PMC9440127
mice neuroblastoma xenograft models oral 50 mg/kg daily for 60 days To evaluate the antitumor activity of Ceritinib monotherapy and its combination with CGM097 in neuroblastoma xenograft models, the results showed that the combination significantly inhibited tumor growth and achieved durable tumor regression. PMC5435462

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02374489 Cholangiocarcinoma PHASE2 TERMINATED 2025-01-18 National Taiwan University Hos... More >>pital, Taipei, 112, Taiwan|National Cheng Kung University Hospital, Taipei, 704, Taiwan Less <<
NCT02289144 Metastatic Anaplastic Thyroid ... More >>Cancer|Locally Advanced Anaplastic, Undifferentiated Thyroid Cancer Less << PHASE2 WITHDRAWN 2025-01-19 UT Southwestern Medical Center... More >>, Dallas, Texas, 75390, United States Less <<
NCT01947608 Non-small Cell Lung Cancer (NS... More >>CLC) Less << NO_LONGER_AVAILABLE - Ironwood Cancer and Research C... More >>enters, Chandler, Arizona, 85224, United States|Banner MDACC, Gilbert, Arizona, 85234, United States|Western Regional Medical Center, Inc., Goodyear, Arizona, 85338, United States|Highlands Oncology Group, Fayetteville, Arkansas, 72703, United States|City of Hope National Medical Center, Duarte, California, 91010, United States|Moores UCSD Cancer Center, La Jolla, California, 92093, United States|St Joseph Heritage Healthcare, Santa Rosa, California, 94503, United States|Stanford University, Stanford, California, 94305-5203, United States|Eastern Connecticut Hematology & Oncology Associates, Norwich, Connecticut, 06360, United States|Advanced Medical Specialties, Miami, Florida, 33176, United States|Peachtree Hematology/Oncology Consultants, Atlanta, Georgia, 30309, United States|Emory University School of Medicine/Winship Cancer Institute, Atlanta, Georgia, 30322, United States|Lurie Children's Hospital of Chicago, Chicago, Illinois, 60611, United States|Indiana University Health Goshen Center for Cancer, Goshen, Indiana, 46526, United States|Johns Hopkins Bayview Hospital, Baltimore, Maryland, 21224, United States|Maryland Oncology Hematology, P.A., Rockville, Maryland, 20850, United States|Massachusetts General Hospital Mass General, Boston, Massachusetts, 02114, United States|Karmanos Cancer Institute, Detroit, Michigan, 48201, United States|Jackson Oncology Associates, Jackson, Mississippi, 39202, United States|Nebraska Cancer Specialist/Missouri Valley Cancer Consortium, Omaha, Nebraska, 68106, United States|Hackensack University Medical Center, Hackensack, New Jersey, 07601, United States|Mercy Clinic Oklahoma Communities Mercy Oncology, Oklahoma City, Oklahoma, 73120-9391, United States|Fox Chase Cancer Center, Philadelphia, Pennsylvania, 19111, United States|Tennessee Cancer Specialists, Knoxville, Tennessee, 37909, United States|University of Utah / Huntsman Cancer Institute, Salt Lake City, Utah, 84112-5820, United States|Seattle Cancer Care Alliance, Seattle, Washington, 98109-1023, United States|University of Wisconsin, Madison, Wisconsin, 53705-2397, United States|Novartis Investigative Site, Caba, Buenos Aires, C1426ANZ, Argentina|Novartis Investigative Site, Buenos Aires, Caba, C1431FWO, Argentina|Novartis Investigative Site, Córdoba, Cordoba, 5000, Argentina|Novartis Investigative Site, Cali, Valle Del Cauca, Colombia|Novartis Investigative Site, Monteria, Colombia|Novartis Investigative Site, Hong Kong, Hong Kong|Novartis Investigative Site, Kowloon, Hong Kong|Novartis Investigative Site, Delhi, 110 085, India|Novartis Investigative Site, Amman, 11941, Jordan|Novartis Investigative Site, Bundang Gu, Gyeonggi Do, 13620, Korea, Republic of|Novartis Investigative Site, Gyeonggi do, Korea, 10408, Korea, Republic of|Novartis Investigative Site, Seoul, Korea, 05505, Korea, Republic of|Novartis Investigative Site, Seoul, Korea, 06351, Korea, Republic of|Novartis Investigative Site, Seoul, Seocho Gu, 06591, Korea, Republic of|Novartis Investigative Site, Seoul, 03080, Korea, Republic of|Novartis Investigative Site, Seoul, 03722, Korea, Republic of|Novartis Investigative Site, Ciudad De Mexico, Distrito Federal, 14080, Mexico|Novartis Investigative Site, Mexico D F, Distrito Federal, 06760, Mexico|Novartis Investigative Site, Mexico, Distrito Federal, 14080, Mexico|Novartis Investigative Site, Taguig City, Metro Manila, 1634, Philippines|Novartis Investigative Site, Quezon City, Philippines|Novartis Investigative Site, Bangkok, 10330, Thailand|Novartis Investigative Site, Bangkok, 10400, Thailand|Novartis Investigative Site, Bangkok, 10700, Thailand Less <<
NCT01634763 Tumors Characterized by Geneti... More >>c Alterations in Anaplastic Lymphoma Kinase (ALK) Less << PHASE1 COMPLETED 2025-01-16 Novartis Investigative Site, S... More >>unto-gun, Shizuoka, 411-8777, Japan|Novartis Investigative Site, Koto, Tokyo, 135-8550, Japan|Novartis Investigative Site, Fukuoka, 811-1395, Japan Less <<
NCT01685138 Non-Small Cell Lung Cancer PHASE2 COMPLETED 2018-01-22 Massachusetts General Hospital... More >> Mass Gen 5, Boston, Massachusetts, 02114, United States|Washington University School of Medicine Washington University (16), Saint Louis, Missouri, 63110, United States|Sarah Cannon Research Institute Drug Ship - 4, Nashville, Tennessee, 37203, United States|U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office, Dallas, Texas, 75390, United States|Novartis Investigative Site, St Leonards, New South Wales, 2065, Australia|Novartis Investigative Site, Franston, Victoria, 3199, Australia|Novartis Investigative Site, Genk, 3600, Belgium|Novartis Investigative Site, Leuven, 3000, Belgium|Novartis Investigative Site, Toronto, Ontario, M5G 2M9, Canada|Novartis Investigative Site, Saskatoon, Saskatchewan, S7N 4H4, Canada|Novartis Investigative Site, Saint Herblain cedex, 44805, France|Novartis Investigative Site, Hong Kong, Hong Kong|Novartis Investigative Site, Avellino, AV, 83100, Italy|Novartis Investigative Site, Genova, GE, 16132, Italy|Novartis Investigative Site, Milano, MI, 20141, Italy|Novartis Investigative Site, Rozzano, MI, 20089, Italy|Novartis Investigative Site, Orbassano, TO, 10043, Italy|Novartis Investigative Site, Nagoya, Aichi, 464 8681, Japan|Novartis Investigative Site, Kashiwa, Chiba, 277 8577, Japan|Novartis Investigative Site, Fukuoka-city, Fukuoka, 811-1395, Japan|Novartis Investigative Site, Akashi, Hyogo, 673-8558, Japan|Novartis Investigative Site, Sayama, Osaka, 589 8511, Japan|Novartis Investigative Site, Sunto Gun, Shizuoka, 411 8777, Japan|Novartis Investigative Site, Chuo-ku, Tokyo, 104-0045, Japan|Novartis Investigative Site, Koto ku, Tokyo, 135 8550, Japan|Novartis Investigative Site, Seoul, Gyeonggi Do, 03080, Korea, Republic of|Novartis Investigative Site, Seoul, Korea, 05505, Korea, Republic of|Novartis Investigative Site, Seoul, Korea, 06351, Korea, Republic of|Novartis Investigative Site, Seoul, 03722, Korea, Republic of|Novartis Investigative Site, Auckland, 1142, New Zealand|Novartis Investigative Site, Oslo, NO-0424, Norway|Novartis Investigative Site, Chelyabinsk, 454087, Russian Federation|Novartis Investigative Site, Moscow, 115478, Russian Federation|Novartis Investigative Site, St-Petersburg, 197022, Russian Federation|Novartis Investigative Site, Singapore, 169610, Singapore|Novartis Investigative Site, Malaga, Andalucia, 29010, Spain|Novartis Investigative Site, Badalona, Catalunya, 08916, Spain|Novartis Investigative Site, Barcelona, Catalunya, 08035, Spain|Novartis Investigative Site, Madrid, 28046, Spain|Novartis Investigative Site, Madrid, 28050, Spain|Novartis Investigative Site, Stockholm, SE 171 76, Sweden|Novartis Investigative Site, Tainan, Taiwan ROC, 70403, Taiwan|Novartis Investigative Site, Taipei, Taiwan, ROC, 11217, Taiwan|Novartis Investigative Site, Taichung, 407, Taiwan|Novartis Investigative Site, Taipei, 10002, Taiwan|Novartis Investigative Site, Songkla, Hat Yai, 90110, Thailand|Novartis Investigative Site, Bangkok, 10330, Thailand|Novartis Investigative Site, Bangkok, 10400, Thailand|Novartis Investigative Site, Bangkok, 10700, Thailand|Novartis Investigative Site, Colchester, CO3 3NB, United Kingdom|Novartis Investigative Site, London, SE1 9RT, United Kingdom Less <<
NCT01742286 ALK-activated Tumors PHASE1 COMPLETED 2019-04-26 Dana Farber Cancer Institute D... More >>ept of Onc, Boston, Massachusetts, 02215, United States|Memorial Sloan Kettering SC - 7, New York, New York, 10017, United States|Cincinnati Children s Hospital Medical Center Dept of Oncology, Cincinnati, Ohio, 45229-3039, United States|St Jude s Childrens Research Hospital Dept of Oncology, Memphis, Tennessee, 38105-2794, United States|Texas Children's Hospital Dept of Oncology, Houston, Texas, 77030, United States|Novartis Investigative Site, Randwick, New South Wales, 2130, Australia|Novartis Investigative Site, Parkville, Victoria, 3052, Australia|Novartis Investigative Site, Toronto, Ontario, M5G 1X8, Canada|Novartis Investigative Site, Paris, 75231, France|Novartis Investigative Site, Villejuif Cedex, 94805, France|Novartis Investigative Site, Koeln, Nordrhein-Westfalen, 50937, Germany|Novartis Investigative Site, Berlin, 13353, Germany|Novartis Investigative Site, Essen, 45147, Germany|Novartis Investigative Site, Milano, MI, 20133, Italy|Novartis Investigative Site, Seoul, 03080, Korea, Republic of|Novartis Investigative Site, Utrecht, CS, 3584, Netherlands|Novartis Investigative Site, Amsterdam, 1105 AZ, Netherlands|Novartis Investigative Site, Rotterdam, 3015 CN, Netherlands|Novartis Investigative Site, Barcelona, Catalunya, 08035, Spain|Novartis Investigative Site, Valencia, Comunidad Valenciana, 46026, Spain|Novartis Investigative Site, Madrid, 28009, Spain|Novartis Investigative Site, West Midlands, Birmingham, B4 6NH, United Kingdom|Novartis Investigative Site, Sutton, Surrey, SM2 5PT, United Kingdom Less <<
NCT02336451 ALK-positive Non-small Cell Lu... More >>ng Cancer Less << PHASE2 COMPLETED 2019-02-06 USC Kenneth Norris Comprehensi... More >>ve Cancer Center SC-3, Los Angeles, California, 90033, United States|Stanford Universtiy Medical Center SC-5, Stanford, California, 94304, United States|Memorial Hospital of South Bend, South Bend, Indiana, 46601, United States|Dana Farber Cancer Institute SC-12, Boston, Massachusetts, 02215, United States|The Ohio State University Comprehensive Cancer Center Ohio State University, Columbus, Ohio, 43221, United States|Southwestern Regional Medical Center, Tulsa, Oklahoma, 74133, United States|Seattle Cancer Care Alliance, Seattle, Washington, 98105, United States|Novartis Investigative Site, Auckland, Australia|Novartis Investigative Site, Leuven, 3000, Belgium|Novartis Investigative Site, Salvador, Bahia, 41253-190, Brazil|Novartis Investigative Site, Porto Alegre, Rio Grande Do Sul, 90610-000, Brazil|Novartis Investigative Site, Natal, RN, 59075 740, Brazil|Novartis Investigative Site, Itajai, SC, 88301-229, Brazil|Novartis Investigative Site, Barretos, SP, 14784 400, Brazil|Novartis Investigative Site, Sao Paulo, SP, 01246 000, Brazil|Novartis Investigative Site, Sao Paulo, 01236 030, Brazil|Novartis Investigative Site, Toronto, Ontario, M5G 2M9, Canada|Novartis Investigative Site, Marseille cedex 20, Bouches Du Rhone, 13915, France|Novartis Investigative Site, Paris, 75970, France|Novartis Investigative Site, Rennes, 35043, France|Novartis Investigative Site, Saint-Herblain Cédex, 44805, France|Novartis Investigative Site, Strasbourg Cedex, 67091, France|Novartis Investigative Site, Villejuif Cedex, 94805, France|Novartis Investigative Site, Bad Berka, 99437, Germany|Novartis Investigative Site, Koeln, 50937, Germany|Novartis Investigative Site, Pokfulam, Hong Kong|Novartis Investigative Site, Livorno, LI, 57124, Italy|Novartis Investigative Site, Monza, MB, 20900, Italy|Novartis Investigative Site, Messina, ME, 98158, Italy|Novartis Investigative Site, Milano, MI, 20133, Italy|Novartis Investigative Site, Milano, MI, 20141, Italy|Novartis Investigative Site, Perugia, PG, 06129, Italy|Novartis Investigative Site, Aviano, PN, 33081, Italy|Novartis Investigative Site, Parma, PR, 43100, Italy|Novartis Investigative Site, Roma, RM, 00155, Italy|Novartis Investigative Site, Orbassano, TO, 10043, Italy|Novartis Investigative Site, Verona, VR, 37126, Italy|Novartis Investigative Site, Napoli, 80131, Italy|Novartis Investigative Site, Seoul, Korea, 05505, Korea, Republic of|Novartis Investigative Site, Seoul, 03080, Korea, Republic of|Novartis Investigative Site, Seoul, 06351, Korea, Republic of|NKI-AVL, Department of Thoracic-Oncology, Amsterdam, 1066 CX, Netherlands|Novartis Investigative Site, Saint Petersburg, 192148, Russian Federation|Novartis Investigative Site, Singapore, 169610, Singapore|Novartis Investigative Site, Malaga, Andalucia, 29010, Spain|Novartis Investigative Site, Barcelona, 08041, Spain|Novartis Investigative Site, Madrid, 28034, Spain|Novartis Investigative Site, Madrid, 28040, Spain|Novartis Investigative Site, Madrid, 28222, Spain|Novartis Investigative Site, Tainan, Taiwan ROC, 70403, Taiwan|Novartis Investigative Site, Taipei, 10002, Taiwan|Novartis Investigative Site, Taipei, 11217, Taiwan|Novartis Investigative Site, Istanbul, TUR, 34098, Turkey|Novartis Investigative Site, Ankara, 06100, Turkey|Novartis Investigative Site, Sutton, Surrey, SM2 5PT, United Kingdom|Novartis Investigative Site, Birmingham, B9 5SS, United Kingdom|Novartis Investigative Site, London, SE1 9RT, United Kingdom Less <<
NCT02186821 Tumors With Aberrations in ALK... More >> or ROS1 Less << PHASE2 TERMINATED 2017-12-13 St Joseph Heritage Healthcare ... More >>St. Joseph Heritage, Santa Rosa, California, 94503, United States|Sarah Cannon Research Institute, Denver, Colorado, 80218, United States|Rocky Mountain Cancer Centers Dept of Rocky Mountain (2), Greenwood Village, Colorado, United States|Florida Cancer Specialists Florida Cancer Specialists (31, Fort Myers, Florida, 33901, United States|Northwestern University Northwestern (6), Chicago, Illinois, 60611, United States|Physicians Clinic of Iowa, Cedar Rapids, Iowa, 52403, United States|Holy Cross Hospital Holy Cross (2), Silver Spring, Maryland, 20910, United States|Southeast Nebraska Oncology, Lincoln, Nebraska, 68510, United States|Comprehensive Cancer Centers of Nevada CCC of Nevada (1), Las Vegas, Nevada, 89109, United States|Duke University Medical Center Seeley G. Mudd Bldg., Durham, North Carolina, 27710, United States|Wake Forest Baptist Health Health Sciences, Winston-Salem, North Carolina, 27157, United States|Sanford Hematology Oncology, Fargo, North Dakota, 58122, United States|Columbus Hematology and Oncology PA Columbus Hem and Onc (2), Columbus, Ohio, 39705, United States|Andrew and Patel Associates, Camp Hill, Pennsylvania, 17011, United States|Rhode Island Hospital Rhode Island Hosp. (2), Providence, Rhode Island, 02903, United States|Sanford University of South Dakota Medical Center Sanford Clinical Research, Sioux Falls, South Dakota, 57104, United States|Oncology Consultants Oncology Group, Houston, Texas, 77024, United States|MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3), Houston, Texas, 77030, United States|Utah Cancer Specialists Utah Cancer Specialists, Salt Lake City, Utah, 84106, United States|Swedish Cancer Institute Swedish Cancer Institute, Seattle, Washington, 98104, United States|Aurora Research Institute, Milwaukee, Wisconsin, 53226, United States Less <<
NCT01950481 Normal Hepatic Function|Impair... More >>ed Hepatic Function Less << PHASE1 COMPLETED 2025-09-16 DaVita Clinical Research-Denve... More >>r, Lakewood, Colorado, 80228, United States|Avail. Clinical Research, LLC, DeLand, Florida, 32720, United States|Clinical Research of Miami, INC CLDK378A2110, Miami, Florida, 33126, United States|Orlando Clinical Research Center, Orlando, Florida, 32086, United States|DaVita Clinical Research, Minneapolis, Minnesota, 55404, United States Less <<
NCT01283516 Tumors Characterized by Geneti... More >>c Abnormalities of ALK Less << PHASE1 COMPLETED 2016-05-03 University of Colorado School ... More >>of Medicine Colorado Univ, Aurora, Colorado, 80045, United States|Massachusetts General Hospital Mass General, Boston, Massachusetts, 02114, United States|Memorial Sloan Kettering MSK, New York, New York, 10017, United States|Fox Chase Cancer Center Fox Chase Cancer (2), Philadelphia, Pennsylvania, 19111, United States|University of Utah / Huntsman Cancer Institute Huntsman, Salt Lake City, Utah, 84103, United States|Seattle Cancer Care Alliance, Seattle, Washington, 98105, United States|Novartis Investigative Site, Melbourne, Victoria, 3000, Australia|Novartis Investigative Site, Leuven, 3000, Belgium|Novartis Investigative Site, Toronto, Ontario, M5G 1Z6, Canada|Novartis Investigative Site, Koeln, Nordrhein-Westfalen, 50937, Germany|Novartis Investigative Site, Essen, 45147, Germany|Novartis Investigative Site, Heidelberg, 69120, Germany|Novartis Investigative Site, Ulm, 89081, Germany|Novartis Investigative Site, Milano, MI, 20141, Italy|Novartis Investigative Site, Rozzano, MI, 20089, Italy|Novartis Investigative Site, Seoul, Korea, 03080, Korea, Republic of|Novartis Investigative Site, Amsterdam, 1066 CX, Netherlands|Novartis Investigative Site, Singapore, 169610, Singapore|Novartis Investigative Site, Barcelona, Catalunya, 08035, Spain|Novartis Investigative Site, Glasgow, Scotland, G12 0YN, United Kingdom|Novartis Investigative Site, Leicester, LE1 5WW, United Kingdom Less <<
NCT02450903 Non-Small-Cell Lung Cancer PHASE2 COMPLETED 2018-05-24 Novartis Investigative Site, N... More >>agoya, Aichi, 464 8681, Japan|Novartis Investigative Site, Kashiwa, Chiba, 277 8577, Japan|Novartis Investigative Site, Fukuoka-city, Fukuoka, 811-1395, Japan|Novartis Investigative Site, Sakyo Ku, Kyoto, 606 8507, Japan|Novartis Investigative Site, Natori, Miyagi, 981-1293, Japan|Novartis Investigative Site, Okayama-city, Okayama, 700-8558, Japan|Novartis Investigative Site, Osaka Sayama, Osaka, 589 8511, Japan|Novartis Investigative Site, Chuo ku, Tokyo, 104 0045, Japan|Novartis Investigative Site, Koto ku, Tokyo, 135 8550, Japan Less <<
NCT01964157 Non-small Cell Lung Cancer (NS... More >>CLC) Less << PHASE2 UNKNOWN 2025-12-19 Yonsei Cancer Center at Yonsei... More >> University Medical Center, Seoul, 03722, Korea, Republic of Less <<
NCT01685060 Non-Small Cell Lung Cancer PHASE2 COMPLETED 2016-03-29 Highlands Oncology Group Dept ... More >>of Highlands Oncology Grp, Fayetteville, Arkansas, 72703, United States|City of Hope National Medical Center Dept of Oncology 2, Duarte, California, 91010-3000, United States|University of California at Los Angeles Reg-5, Los Angeles, California, 90095, United States|University of California at San Diego, Moores Cancer Ctr SC, San Diego, California, 92103, United States|Stanford University Medical Center Stanford Cancer Center(2), Stanford, California, 94304, United States|University of Colorado Hospital SC, Aurora, Colorado, 80045, United States|Emory University School of Medicine/Winship Cancer Institute Dept of Oncology, Atlanta, Georgia, 30322, United States|University of Chicago Medical Center SC, Chicago, Illinois, 60637, United States|University of Kansas Cancer Center DeptofUofKansas CancerCenter-2, Kansas City, Kansas, 66160, United States|Cancer Center of Kansas Dept of CCK, Wichita, Kansas, 67214-3728, United States|Maryland Oncology Hematology, P.A. SC, Rockville, Maryland, 20850, United States|Massachusetts General Hospital Mass General, Boston, Massachusetts, 02114, United States|Levine Cancer Institute SC 1, Charlotte, North Carolina, 28203, United States|Sarah Cannon Research Institute Drug Ship - 4, Nashville, Tennessee, 37203, United States|U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office, Dallas, Texas, 75390, United States|Seattle Cancer Care Alliance SC-1, Seattle, Washington, 98105, United States|University of Wisconsin Univ Wisc 2, Madison, Wisconsin, 53792, United States|Novartis Investigative Site, Edmonton, Alberta, T6G 1Z2, Canada|Novartis Investigative Site, Oshawa, Ontario, L1G 2B9, Canada|Novartis Investigative Site, Toronto, Ontario, M5G 2M9, Canada|Novartis Investigative Site, Marseille cedex 20, 13915, France|Novartis Investigative Site, Paris, 75970, France|Novartis Investigative Site, Koeln, Nordrhein-Westfalen, 50937, Germany|Novartis Investigative Site, Heidelberg, 69120, Germany|Novartis Investigative Site, Hong Kong, Hong Kong|Novartis Investigative Site, Avellino, AV, 83100, Italy|Novartis Investigative Site, Livorno, LI, 57124, Italy|Novartis Investigative Site, Monza, MB, 20900, Italy|Novartis Investigative Site, Milano, MI, 20141, Italy|Novartis Investigative Site, Perugia, PG, 06129, Italy|Novartis Investigative Site, Parma, PR, 43100, Italy|Novartis Investigative Site, Nagoya, Aichi, 464-8681, Japan|Novartis Investigative Site, Kashiwa, Chiba, 277-8577, Japan|Novartis Investigative Site, Akashi, Hyogo, 673-8558, Japan|Novartis Investigative Site, Okayama-city, Okayama, 700-8558, Japan|Novartis Investigative Site, OsakaSayama, Osaka, 589-8511, Japan|Novartis Investigative Site, Sunto-gun, Shizuoka, 411-8777, Japan|Novartis Investigative Site, Chuo-ku, Tokyo, 104-0045, Japan|Novartis Investigative Site, Koto, Tokyo, 135-8550, Japan|Novartis Investigative Site, Fukuoka, 811-1395, Japan|Novartis Investigative Site, Seoul, Korea, 03080, Korea, Republic of|Novartis Investigative Site, Seoul, Korea, 03722, Korea, Republic of|Novartis Investigative Site, Seoul, Korea, 06351, Korea, Republic of|Novartis Investigative Site, Amsterdam, 1081 HV, Netherlands|Novartis Investigative Site, Groningen, 9713 GZ, Netherlands|Novartis Investigative Site, Maastricht, 5800, Netherlands|Novartis Investigative Site, Singapore, 169610, Singapore|Novartis Investigative Site, Sevilla, Andalucia, 41013, Spain|Novartis Investigative Site, Barcelona, Catalunya, 08035, Spain|Novartis Investigative Site, La Coruna, Galicia, 15006, Spain|Novartis Investigative Site, Madrid, 28046, Spain|Novartis Investigative Site, London, SE1 9RT, United Kingdom Less <<
NCT02040870 Non-Small Cell Lung Cancer PHASE1|PHASE2 COMPLETED 2017-07-27 Novartis Investigative Site, B... More >>eijing, Beijing, 100730, China|Novartis Investigative Site, Chongqing, Chongqing, 400037, China|Novartis Investigative Site, Guangzhou, Guangdong, 51000, China|Novartis Investigative Site, Changchun, Jilin, 130012, China|Novartis Investigative Site, Shanghai, Shanghai, 200032, China|Novartis Investigative Site, Shanghai, Shanghai, 200433, China|Novartis Investigative Site, Xi'an, Shanxi, 710038, China|Novartis Investigative Site, Chengdu, Sichuan, 610041, China|Novartis Investigative Site, Hangzhou, Zhejiang, 310003, China|Novartis Investigative Site, Beijing, 100021, China|Novartis Investigative Site, Beijing, 100036, China|Novartis Investigative Site, Beijing, 100039, China|Novartis Investigative Site, Chongqing, 400038, China|Novartis Investigative Site, Guang Dong Province, 510120, China|Novartis Investigative Site, Guangzhou, 510060, China Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.79mL

0.36mL

0.18mL

8.96mL

1.79mL

0.90mL

17.92mL

3.58mL

1.79mL

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

 

Historical Records

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