The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Dasatinib (BMS-354825) Pharmacokinetics and Pharmacodynamic Biomarkers in Animal Models Predict Optimal Clinical Exposure
Abstract
Purpose Chronic myeloid leukemia (CML) is caused by reciprocal translocation between chromosomes 9 and 22, forming BCR-ABL, a constitutively activated tyrosine kinase. Imatinib mesylate, a selective inhibitor of BCR-ABL, represents current frontline therapy for CML; however, emerging evidence suggests that drug resistance to imatinib may limit its long-term success. To improve treatment options, dasatinib (BMS-354825) was developed as a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC family kinases. To date, dasatinib has shown promising anti-leukemic activity in preclinical models of CML and in phase I/II clinical studies in patients with imatinib-resistant or imatinib-intolerant disease. Experimental design The pharmacokinetic and pharmacodynamic biomarkers of dasatinib were investigated in K562 human CML xenografts grown s.c. in severe combined immunodeficient mice. Tumoral levels of phospho-BCR-ABL/phospho-CrkL were determined by Western blot. Results Following a single oral administration of dasatinib at a preclinical efficacious dose of 1.25 or 2.5 mg/kg, tumoral phospho-BCR-ABL/phospho-CrkL were maximally inhibited at approximately 3 hours and recovered to basal levels by 24 hours. The time course and extent of the inhibition correlated with the plasma levels of dasatinib in mice. Pharmacokinetic/biomarker modeling predicted that the plasma concentration of dasatinib required to inhibit 90% of phospho-BCR-ABL in vivo was 10.9 ng/mL in mice and 14.6 ng/m…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dasatinib and quercetin are cleared within 48 h of the last dose.
“D and Q are cleared within 48 h of the last dose (Luo et al., 2006; Piantelli et al., 2006).”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Luo et al., 2006
Citations
Cites
O'Hare, T., Walters, D. K., Stoffregen, E. P., Jia, T., Manley, P. W., Mestan, J., Cowan-Jacob, S. W., Lee, F. Y., Heinrich, M. C., Deininger, M. W. N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0259 · Cited by 1,036
Self-citation
Flagged first, then by citations
Research works printed but not linked: 35
- Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990;247:824–30. · DOI
- Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005;105:2640–53. · DOI
- Nowell P, Hungerford DA. A minute chromosome in human chronic granulocytic leukemia. Science 1960;132:1497.
- Sawyers CL. Chronic myeloid leukemia. N Engl J Med 1999;340:1330–40. · DOI
- O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994–1004. · DOI
- Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031–7. · DOI
- Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001;344:1038–42. · DOI · Paper page
- Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 2002;99:3530–9. · DOI
- Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002;99:1928–37. · DOI
- Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002;346:645–52. · DOI
- Kantarjian H, Talpaz M, O'Brien S, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood 2004;103:2873–8. · DOI
- Kantarjian HM, Cortes JE, O'Brien S, et al. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-α. Blood 2004;104:1979–88. · DOI
- Donato NJ, Wu JY, Stapley J, et al. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood 2003;101:690–8. · DOI
- Donato NJ, Wu JY, Kong LY, Lee FY, Talpaz M. The SRC/ABL inhibitor BMS-354825 overcomes resistance to imatinib mesylate in chronic myelogenous leukemia cells through multiple mechanisms. In: The American Society of Hematology 46th Annual Meeting; 2004. · DOI
- Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305:399–401. · DOI
- Sawyers CL, Kantarjian HM, Shah NP, et al. Dasatinib (BMS-354825) in patients with chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to imatinib: update of a phase I study. Blood 2005;106. · DOI
- Guilhot F, Apperley JF, Shah NP, et al. Phase II study of dasatinib in patients with accelerated phase chronic myeloid leukemia (CML) who are resistant or intolerant to imatinib: first results of the CA180005 ‘START-A’ study. Blood 2005;106. · DOI
- Talpaz M, Rousselot P, Kim DW, et al. A phase II study of dasatinib in patients with chronic myeloid leukemia (CML) in myeloid blast crisis who are resistant or intolerant to imatinib: first results of the CA180006 ‘START-B’ study. Blood 2005;106. · DOI
- Hochhaus A, Baccarani M, Sawyers CL, et al. Efficacy of dasatinib in patients with chronic phase Philadelphia chromosome-positive CML resistant or intolerant to imatinib: first results of the CA180013 ‘START-C’ phase II study. Blood 2005;106. · DOI
- Ottmann O, Martinelli G, Dombret H, et al. A phase II study of dasatinib in patients with chronic myeloid leukemia (CML) in lymphoid blast crisis or Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to imatinib: the ‘START-L’ CA180015 study. Blood 2005;106. · DOI
- Park JW, Kerbel RS, Kelloff GJ, et al. Rationale for biomarkers and surrogate end points in mechanism-driven oncology drug development. Clin Cancer Res 2004;10:3885–96. · DOI
- Wolf M, Swaisland H, Averbuch S. Development of the novel biologically targeted anticancer agent gefitinib: determining the optimum dose for clinical efficacy. Clin Cancer Res 2004;10:4607–13. · DOI
- Nichols GL, Raines MA, Vera JC, Lacomis L, Tempst P, Golde DW. Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine phosphoprotein in chronic myelogenous leukemia cells. Blood 1994;84:2912–8. · DOI
- Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ. Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. J Biol Chem 1994;269:22925–8. · DOI
- Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000;105:3–7. · DOI
- Albanell J, Rojo F, Baselga J. Pharmacodynamic studies with the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839. Semin Oncol 2001;28:56–66. · DOI
- Baselga J, Rischin D, Ranson M, et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 2002;20:4292–302. · DOI · Paper page
- Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996;14:737–44. · DOI
- Lipton A, Ali SM, Leitzel K, et al. Elevated serum HER-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer. J Clin Oncol 2002;20:1467–72. · DOI
- Luo FR, Yang Z, Dong H, et al. Prediction of active drug plasma concentrations achieved in cancer patients by pharmacodynamic biomarkers identified from the geo human colon carcinoma xenograft model. Clin Cancer Res 2005;11:1–8. · DOI
- Peng B, Hayes M, Resta D, et al. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol 2004;22:935–42. · DOI
- Ranson M, Hammond LA, Ferry D, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 2002;20:2240–50. · DOI
- Freireich E, Gehan EA, Rall D, Schmidt L, Skipper H. Cancer Chemother Rep 1966;50:219.
- Sawyers CL, Shah NP, Kantarjian HM, et al. A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant accelerated and blast phase chronic myeloid leukemia (CML): results from CA180002. 2005 ASCO Annual Meeting; 2005. · DOI
- Talpaz M, Kantarjian HM, Paquette R, et al. A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant chronic phase chronic myeloid leukemia (CML): results from CA180002. In: 2005 ASCO Annual Meeting; 2005. · DOI
Cited by
Sorted by citations
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584
“D and Q are cleared within 48 h of the last dose (Luo et al., 2006; Piantelli et al., 2006).”
BackgroundAkhmetshina, A., Dees, C., Pileckyte, M., Maurer, B., Axmann, R., Jüngel, A., Zwerina, J., Gay, S., Schett, G., Distler, O., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-105627 · Cited by 187
Metadata
- Authors
- Luo, F. R., Yang, Z., Camuso, A., Smykla, R., McGlinchey, K., Fager, K., Flefleh, C., Castaneda, S., Inigo, I., Kan, D., Wen, M.-L., Kramer, R., Blackwood-Chirchir, A., & Lee, F. Y.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- Authors' Affiliation: Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, New Jersey
- Venue
- Clinical Cancer Research
- Published
- 2006-12-01
- Volume
- 12
- Issue
- 23
- Pages
- 7180-7186
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2029254213
- Cited by
- 151
- References
- 1
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 7 · 2013: 9 · 2012: 15
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- dasatinib, BCR-ABL, chronic myeloid leukemia, pharmacokinetics, pharmacodynamic biomarkers, imatinib resistance, Src family kinases, kinase inhibition, therapeutic drug monitoring, plasma concentration
- MeSH terms
- Dasatinib, Administration, Oral, Animals, Antineoplastic Agents, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Humans, Injections, Intravenous, Nuclear Proteins, Predictive Value of Tests, Pyrimidines, Structure-Activity Relationship, Thiazoles, Time Factors, Transplantation, Heterologous, Biomarkers, Tumor, Blotting, Western, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Fusion Proteins, bcr-abl, Mice, SCID, Xenograft Model Antitumor Assays, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
