DOCSLIB.ORG

Product Data Sheet

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Product Data Sheet MedK Product data sheet MedKoo Cat#: 205990 Name: Radotinib CAS#: 926037-48-1 (free base) F F F Chemical Formula: C27H21F3N8O Exact Mass: 530.1790 O N Molecular Weight: 530.50 H Product supplied as: Powder N N N N N Purity (by HPLC): ≥ 98% H N Shipping conditions Ambient temperature N Storage conditions: Powder: -20°C 3 years; 4°C 2 years. In solvent: -80°C 3 months; -20°C 2 weeks. 1. Product description: Radotinib, also known as IY-5511, is an orally available, a second-generation tyrosine kinase inhibitor of Bcr-Abl fusion protein and the platelet-derived growth factor receptor (PDGFR), with potential antineoplastic activity. Upon administration, radotinib specifically inhibits the Bcr-Abl fusion protein, an abnormal enzyme expressed in Philadelphia chromosome-positive chronic myeloid leukemia (CML) cells. In addition, this agent also inhibits PDGFR thereby blocking PDGFR-mediated signal transduction pathways. 2. CoA, QC data, SDS, and handling instruction SDS and handling instruction, CoA with copies of QC data (NMR, HPLC and MS analytical spectra) can be downloaded from the product web page under “QC And Documents” section. Note: copies of analytical spectra may not be available if the product is being supplied by MedKoo partners. Whether the product was made by MedKoo or provided by its partners, the quality is 100% guaranteed. 3. Solubility data Solvent Max Conc. mg/mL Max Conc. mM DMSO 10.0 18.9 4. Stock solution preparation table: Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg 1 mM 1.89 mL 9.43 mL 18.85 mL 5 mM 0.38 mL 1.89 mL 3.77 mL 10 mM 0.19 mL 0.94 mL 1.89 mL 50 mM 0.04 mL 0.19 mL 0.38 mL 5. Molarity Calculator, Reconstitution Calculator, Dilution Calculator Please refer the product web page under section of “Calculator” 6. Recommended literature which reported protocols for in vitro and in vivo study In vitro study 1. Heo SK, Noh EK, Jeong YK, Ju LJ, Sung JY, Yu HM, Cheon J, Koh S, Min YJ, Choi Y, Jo JC. Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression. Tumour Biol. 2019 May;41(5):1010428319848612. doi: 10.1177/1010428319848612. PMID: 31074363. 2. Lee S, Kim S, Park YJ, Yun SP, Kwon SH, Kim D, Kim DY, Shin JS, Cho DJ, Lee GY, Ju HS, Yun HJ, Park JH, Kim WR, Jung EA, Lee S, Ko HS. The c-Abl inhibitor, Radotinib HCl, is neuroprotective in a preclinical Parkinson's disease mouse model. Hum Mol Genet. 2018 Jul 1;27(13):2344-2356. doi: 10.1093/hmg/ddy143. PMID: 29897434; PMCID: PMC6005030. In vivo study 1. Heo SK, Noh EK, Jeong YK, Ju LJ, Sung JY, Yu HM, Cheon J, Koh S, Min YJ, Choi Y, Jo JC. Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression. Tumour Biol. 2019 May;41(5):1010428319848612. doi: 10.1177/1010428319848612. PMID: 31074363. 2. Lee S, Kim S, Park YJ, Yun SP, Kwon SH, Kim D, Kim DY, Shin JS, Cho DJ, Lee GY, Ju HS, Yun HJ, Park JH, Kim WR, Jung EA, Lee S, Ko HS. The c-Abl inhibitor, Radotinib HCl, is neuroprotective in a preclinical Parkinson's disease mouse model. Hum Mol Genet. 2018 Jul 1;27(13):2344-2356. doi: 10.1093/hmg/ddy143. PMID: 29897434; PMCID: PMC6005030. MedKoo Biosciences || http://www.medkoo.com || [email protected] 2500 Gateway Centre Blvd Suite 400, Morrisville, NC27560, USA. Tel: 919-636-5577, Fax: 919-980-4831 MedK Product data sheet 7. Bioactivity Biological target: Radotinib (IY-5511) is a BCR-ABL1 tyrosine kinase inhibitor with IC50 of 34 nM. In vitro activity Radotinib significantly decreased the expression of cyclin-dependent kinase 1 and cyclin B1, the key regulators of G2/M phase, and inhibited the expression of Aurora kinase A and Aurora kinase B in acute myeloid leukemia cells. In addition, radotinib decreased the expression and binding between p-Aurora kinase A and TPX2, which are required for spindle assembly. Furthermore, it reduced Aurora kinase A and polo-like kinase 1 phosphorylation and suppressed the expression of α-, β-, and γ-tubulin in acute myeloid leukemia cells. Reference: Tumour Biol. 2019 May;41(5):1010428319848612. https://journals.sagepub.com/doi/10.1177/1010428319848612?url_ver=Z39.88- 2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed In vivo activity The neuroprotective efficacy of Radotinib HCl, a brain penetrant c-Abl inhibitor, was evaluated in a pre-clinical model of Parkinson’s disease (PD). Administration of Radotinib HCl inhibited c-Abl activation and prevented dopaminergic neuron loss, neuroinflammation and behavioral deficits following α-synuclein PFF (preformed fibrils)-induced toxicity in vivo. Reference: Hum Mol Genet. 2018 Jul 1;27(13):2344-2356. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005030/ Note: The information listed here was extracted from literature. MedKoo has not independently retested and confirmed the accuracy of these methods. Customer should use it just for a reference only. MedKoo Biosciences || http://www.medkoo.com || [email protected] 2500 Gateway Centre Blvd Suite 400, Morrisville, NC27560, USA. Tel: 919-636-5577, Fax: 919-980-4831 .
Load more

Recommended publications
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Radotinib Item No. 19923 CAS Registry No.: 926037-48-1 Formal Name: 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5- (trifluoromethyl)phenyl]-3-[[4-(2-pyrazinyl)-2- N pyrimidinyl]amino]-benzamide H N Synonym: IY-5511 N N MF: C H F N O N N N 27 21 3 8 O FW: 530.5 H N Purity: ≥98% UV/Vis.: λmax: 215, 270 nm CF3 Supplied as: A crystalline solid Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Radotinib is supplied as a crystalline solid. A stock solution may be made by dissolving the radotinib in the solvent of choice. Radotinib is soluble in organic solvents such as DMSO and dimethyl formamide, which should be purged with an inert gas. The solubility of radotinib in these solvents is approximately 10 and 3 mg/ml, respectively. Description Radotinib is a selective second generation tyrosine kinase inhibitor that targets both the wild-type and mutant forms of Bcr-Abl, with an IC50 value of 30.6 nM in Ba/F3 human chronic myeloid leukemia cells expressing the wild-type form.1 Radotinib also inhibits platelet-derived growth factor receptors (PDGFRs) α 2,3 and β with IC50 values of 75.5 and 130 nM, respectively. Binding of radotinib to Bcr-Abl in vitro inhibits the phosphorylation of the downstream signaling mediator CrkL.3 In acute myeloid leukemia cells, in vitro treatment with radotinib at doses of 10-100 µM reduces viability, activates the mitochondrial apoptosis pathway, and promotes expression of the differentiation marker CD11b.2 References 1.
    [Show full text]
  • Radotinib Induces Apoptosis of Cd11b+ Cells Differentiated from Acute Myeloid Leukemia Cells
    RESEARCH ARTICLE Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells Sook-Kyoung Heo1, Eui-Kyu Noh2, Dong-Joon Yoon1, Jae-Cheol Jo2, Yunsuk Choi2, SuJin Koh2, Jin Ho Baek2, Jae-Hoo Park3, Young Joo Min2, Hawk Kim1,2* 1 Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 682-060, Republic of Korea, 2 Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 682-714, Republic of Korea, 3 Department of Hematology and Oncology, Myongji Hospital, Gyeonggi-do, 412-270, Republic of Korea * [email protected] Abstract Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI), is approved for the sec- OPEN ACCESS ond-line treatment of chronic myeloid leukemia (CML) in South Korea. However, therapeutic Citation: Heo S-K, Noh E-K, Yoon D-J, Jo J-C, Choi effects of radotinib in acute myeloid leukemia (AML) are unknown. In the present study, we Y, Koh S, et al. (2015) Radotinib Induces Apoptosis of demonstrate that radotinib significantly decreases the viability of AML cells in a dose-de- CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells. PLoS ONE 10(6): e0129853. pendent manner. Kasumi-1 cells were more sensitive to radotinib than NB4, HL60, or THP- doi:10.1371/journal.pone.0129853 1 cell lines. Furthermore, radotinib induced CD11b expression in NB4, THP-1, and Kasumi- Academic Editor: Rajasingh Johnson, University of 1 cells either in presence or absence of all trans-retinoic acid (ATRA). We found that radoti- Kansas Medical Center, UNITED STATES nib promoted differentiation and induced CD11b expression in AML cells by downregulating Received: March 30, 2015 LYN.
    [Show full text]
  • Atezolizumab Plus Nab-Paclitaxel As First-Line Treatment for Unresectable, Locally Advanced Or Metastatic Triple-Negative Breast
    Articles Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial Peter Schmid*, Hope S Rugo*, Sylvia Adams, Andreas Schneeweiss, Carlos H Barrios, Hiroji Iwata, Véronique Diéras, Volkmar Henschel, Luciana Molinero, Stephen Y Chui, Vidya Maiya, Amreen Husain, Eric P Winer, Sherene Loi, Leisha A Emens, for the IMpassion130 Investigators† Summary Lancet Oncol 2020; 21: 44–59 Background Immunotherapy in combination with chemotherapy has shown promising efficacy across many different Published Online tumour types. We report the prespecified second interim overall survival analysis of the phase 3 IMpassion130 study November 27, 2019 assessing the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with unresectable, locally advanced or https://doi.org/10.1016/ metastatic triple-negative breast cancer. S1470-2045(19)30689-8 See Comment page 3 Methods In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 246 academic centres and *Contributed equally community oncology practices in 41 countries, patients aged 18 years or older, with previously untreated, histologically †Investigators are listed in the documented, locally advanced or metastatic triple-negative breast cancer, and Eastern Cooperative Oncology Group appendix performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) using a permuted block method Barts Cancer Institute, Queen Mary University of London, (block size of four) and an interactive voice–web response system. Randomisation was stratified by previous taxane London, UK (Prof P Schmid MD); use, liver metastases, and PD-L1 expression on tumour-infiltrating immune cells.
    [Show full text]
  • Early Subclinical Biomarkers in Onco-Cardiology to Prevent
    maco har log P y: r O la u p Yajun et al., Cardiovasc Pharm Open Access 2016, 5:3 c e n s a A v c o DOI: 10.4172/2329-6607.1000183 c i e d r s a s C Cardiovascular Pharmacology: Open Access ISSN: 2329-6607 Review Article OpenOpen Access Access Early Subclinical Biomarkers in Onco-Cardiology to Prevent Cardiac Death Yajun Gu1, Bumei Zhang2, Hongwei Fu1,3, Yichao Wang1 and Yunde Liu1* 1School of Medical Laboratory, Tianjin Medical University, Tianjin, China 2Department of Family Planning, the Second Hospital of Tianjin Medical University, Tianjin, China 3Tianjin Medical University General Hospital, Tianjin, China Abstract Recent oncologic treatment has been associated with cardiovascular complications, such as hypertension, metabolic derangements, thrombosis, arrhythmia, and even cardiac death. Careful attention to detailed cardiac evaluation is required to optimize the anticancer treatment and prevent heart failure of patients undergoing chemoradiotherapy. Classical cardiovascular biomarkers like ANP, BNP, ProANP, NT-ProBNP, hsTnI, hsTnT, adropin, copeptin, and ET-1 are indicative of toxic effects in cancer patients with radiation, chemotherapy, and neoadjuvant treatment. Recently, miRNAs (i.e., miR-29, miR-146, miR-208, and miR-216) in the peripheral blood or exosome- derived miRNAs are attractive as novel biomarkers for drug-induced cardiotoxicity due to their highly conserved sequence and stability in body fluids. The anticancer treatment could lead to detectable increases of miRNAs in the absence of traditional cardiac biomarkers or cardiac remodeling. Circulating cardiovascular biomarkers provide earlier detection of cardiotoxicity from cancer treatments before irreversible damage occurs. An increased understanding of the potential roles and mechanisms may help to reveal the crosstalk between cancer therapy and cardiac issues.
    [Show full text]
  • Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia
    cancers Review Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia Kalpana K. Bhanumathy 1,*, Amrutha Balagopal 1, Frederick S. Vizeacoumar 2 , Franco J. Vizeacoumar 1,3, Andrew Freywald 2 and Vincenzo Giambra 4,* 1 Division of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; [email protected] (A.B.); [email protected] (F.J.V.) 2 Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; [email protected] (F.S.V.); [email protected] (A.F.) 3 Cancer Research Department, Saskatchewan Cancer Agency, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada 4 Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, FG, Italy * Correspondence: [email protected] (K.K.B.); [email protected] (V.G.); Tel.: +1-(306)-716-7456 (K.K.B.); +39-0882-416574 (V.G.) Simple Summary: Protein phosphorylation is a key regulatory mechanism that controls a wide variety of cellular responses. This process is catalysed by the members of the protein kinase su- perfamily that are classified into two main families based on their ability to phosphorylate either tyrosine or serine and threonine residues in their substrates. Massive research efforts have been invested in dissecting the functions of tyrosine kinases, revealing their importance in the initiation and progression of human malignancies. Based on these investigations, numerous tyrosine kinase inhibitors have been included in clinical protocols and proved to be effective in targeted therapies for various haematological malignancies.
    [Show full text]
  • 1. Recommendations of the Ndac (Oncology and Hematology) Held on 10.12.2011
    1. RECOMMENDATIONS OF THE NDAC (ONCOLOGY AND HEMATOLOGY) HELD ON 10.12.2011:- The NDAC (Oncology and Hematology) deliberated the proposals on 10.12.2011 and recommended the following:- AGENDA NAME OF DRUG RECOMMENDATIONS NO. Global Clinical Trials Recommended for giving permission for clinical trial subject to condition that trasuzumab naive patient arm should be excluded from the study, as patients cannot be left untreated of trastuzumab therapy / or 1 Afatinib treated with only investigational drug. Patients aged 18 to 65 years should be included in the study. Recommended for giving permission for clinical trial subject to the following conditions:- ICD is very extensive and too technical for the 2 Netupitant/ patient to understand. It should be simplified. Palonosetron Definite statistical tests for the comparison of primary and secondary endpoints should be incorporated in the protocol. Recommended for giving permission for clinical trial subject to the following conditions:- Periodic ophthalmic examination should be performed at every visit as the drug is reported to have ophthalmological side effects in 53 % cases in 3 Crizotinib phase 2 study. Patients aged 18 to 65 years should be included in the protocol. Method for causality assessment by the investigator should be included in the protocol. New Drugs Approved with the condition that structured post marketing trial (Phase 4) should be conducted in 4. Indian population. Report of post marketing trials Crizotinib ongoing in other countries when completed should be submitted. 5. Abiraterone Approved with condition of conducting Post Acetate Marketing trial (Phase IV) in Indian population to monitor the adverse effects. Report of post marketing trials ongoing in other countries when completed should be submitted.
    [Show full text]
  • Teratogenic Effect of Radotinib: Case Report JUYOUNG CHEON, JUNG WHAN AHN, KYUNG MIN PARK, GUISERA LEE and YUN SUNG JO
    ANTICANCER RESEARCH 36 : 6599-6602 (2016) doi:10.21873/anticanres.11265 Teratogenic Effect of Radotinib: Case Report JUYOUNG CHEON, JUNG WHAN AHN, KYUNG MIN PARK, GUISERA LEE and YUN SUNG JO Department of Obstetrics and Gynecology, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea Abstract. Background: Simultaneous presentation of Case Report pregnancy and chronic myeloid leukemia (CML) is rare. Tyrosine kinase inhibitors (TKIs) are rarely used in A 19-year-old patient, gravida 1 para 0, was referred for pregnancy. There is almost no information on the effect of amenorrhea for 7 weeks 6 days. The patient had been recently developed TKIs on the fetus. Case Report: A 22- diagnosed with CML 1 year earlier and had been taking year-old woman became pregnant while using radotinib, a 200 mg radotinib twice daily orally for 1 year. Six months novel TKI for CML. She was concerned about the possible before referral, in chronic phase, a complete cytogenic response teratogenic effect of radotinib; hence the first pregnancy was was achieved. Normally, the patient had regular menstruation. terminated. The patient underwent full-term delivery at the The result of urine human chorionic gonadotropin (HCG) test second pregnancy. The infant had facial deformity and was positive and the ultrasound examination showed that G- congenital laryngomalacia. Conclusion: We witnessed sac was 1.26 cm. The fetal pole measured 2.4 mm (5 weeks 5 structural abnormality when the patient used radotinib days of gestation). Fetal heart beat was 105 bpm/min. She was during the first trimester of pregnancy.
    [Show full text]
  • Breakthrough Biomedical Philanthropy
    Breakthrough Biomedical Philanthropy May12, 2016 Why is cancer so hard to cure? Tony Hunter 1971 National Cancer Act National Cancer Act Signed into law by President Nixon December 23, 1971 The Director of National Cancer Institute was given authorities under the act that included: • Create new Cancer Centers and manpower training programs • Appoint advisory committees, allowing the director to explore new issues/opportunities. • Expand the physical location at NIH and other research facilities across the country. • AwardThis contracts was for research Nixon’s “moonshot” to • Collaborate with other federal, state, or local public agencies and private industry • Conduct cancer control activitiescure cancer • Establish an international cancer research data bank that collects, catalogues, stores, and disseminates results of cancer research • Award research grants Since 1971 the NCI has spent over $140 billion on cancer research Cancer remains a scourge worldwide • 14 million cancers diagnosed worldwide in 2012 with 8 million deaths, with half of the cancers occurring in underdeveloped countries • Lung cancer accounts for 20% of all cancers world wide, and breast cancers 10% of all cancers • In the United States,1,665,540 new cancer cases were diagnosed and 585,720 cancer deaths occurred in 2014 Cancer is about to overtake heart disease as the leading cause of death in the US US Mortality Data - 2013 No. of % of all Rank Cause of Death deaths deaths 1. Heart diseases 611,105 32.6 2. Cancer 584,881 30.9 3. Chronic lower respiratory diseases 149,205 7.4 4. Accidents 130,557 6.8 5. Cerebrovascular diseases 117,176 6.4 6.
    [Show full text]
  • Determination of a Radotinib Dosage Regimen Based on Dose–
    Cancer Medicine Open Access ORIGINAL RESEARCH Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia Hayeon Noh1, Su Young Jung2,3, Jae-Yong Kwak4, Sung-Hyun Kim5, Suk Joong Oh6, Dae Young Zang7, Suhyun Lee2,3, Hye Lin Park8, Dae Jin Jo8, Jae Soo Shin8, Young Rok Do9, Dong-Wook Kim10,* & Jangik I. Lee2,3,* 1Department of Pharmacy, College of Pharmacy, Yonsei University, Incheon, Korea 2Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea 3Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea 4Chonbuk National University Medical School & Hospital, Jeonju, Korea 5Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 6Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea 7Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea 8Central Research Institute, IL-YANG Pharmaceutical Co., Ltd., Yongin, Korea 9Department of Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea 10Seoul St. Mary’s Hospital, Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea Keywords Abstract Chronic myeloid leukemia, dose determination, dose–response relationship, Radotinib is a second-­generation BCR-ABL1 tyrosine kinase inhibitor approved radotinib, tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia in chronic phase (CP-­CML). Here, using the data from a Phase 3 study conducted in patients with newly Correspondence diagnosed CP-­CML, the dose–efficacy as well as dose–safety relationship analyses Jangik I. Lee, Department of Pharmacy, were performed to determine a safe and effective initial dosage regimen of College of Pharmacy, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul radotinib.
    [Show full text]
  • Kinase Drug Discovery 20 Years After Imatinib: Progress and Future Directions
    REVIEWS Kinase drug discovery 20 years after imatinib: progress and future directions Philip Cohen 1 ✉ , Darren Cross 2 ✉ and Pasi A. Jänne 3 ✉ Abstract | Protein kinases regulate nearly all aspects of cell life, and alterations in their expression, or mutations in their genes, cause cancer and other diseases. Here, we review the remarkable progress made over the past 20 years in improving the potency and specificity of small-molecule inhibitors of protein and lipid kinases, resulting in the approval of more than 70 new drugs since imatinib was approved in 2001. These compounds have had a significant impact on the way in which we now treat cancers and non- cancerous conditions. We discuss how the challenge of drug resistance to kinase inhibitors is being met and the future of kinase drug discovery. Protein kinases In 2001, the first kinase inhibitor, imatinib, received FDA entered clinical trials in 1998, changed the perception Enzymes that catalyse transfer approval, providing the catalyst for an article with the of protein kinases as drug targets, which had previously of the γ- phosphate of ATP provocative title ‘Protein kinases — the major drug tar- received scepticism from many pharmaceutical com- to amino acid side chains in gets of the twenty- first century?’1. Imatinib inhibits the panies. Since then, hundreds of protein kinase inhibi- substrate proteins, such as serine, threonine and tyrosine Abelson (ABL) tyrosine kinase, which is expressed as a tors have been developed and tested in humans and, at residues. deregulated fusion protein, termed BCR–ABL, in nearly the time of writing, 76 have been approved for clinical all cases of chronic myeloid leukaemia (CML)2 and is use, mainly for the treatment of various cancers (FiG.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Functional Properties of KIT Mutations Are
    Published OnlineFirst June 10, 2019; DOI: 10.1158/1078-0432.CCR-18-1897 Clinical Trials: Targeted Therapy Clinical Cancer Research Functional Properties of KIT Mutations Are Associated with Differential Clinical Outcomes and Response to Targeted Therapeutics in CBF Acute Myeloid Leukemia Katherine Tarlock1,2,Todd A. Alonzo3,4,Yi-Cheng Wang4, Robert B.Gerbing4, Rhonda Ries1, Michael R. Loken5, Laura Pardo5, Tiffany Hylkema1, Jason Joaquin1, Leela Sarukkai1, Susana C. Raimondi6, Betsy Hirsch7, Lillian Sung8, Richard Aplenc9, Irwin Bernstein1,2, Alan S. Gamis10, Soheil Meshinchi1,2, and Jessica A. Pollard11,12 Abstract þ Purpose: KIT mutations (KIT ) are common in core bind- (10%) both exons, and 3 (5%) alternative exons. Functional ing factor (CBF) AML and have been associated with varying studies demonstrated that E17, but not E8, mutations result prognostic significance. We sought to define the functional in aberrant KIT phosphorylation and growth. TKI exposure and clinical significance of distinct KIT mutations in CBF significantly affected growth of E17, but not E8, transfected þ pediatric AML. cells. Patients with KIT CBF AML had overall survival similar À Patients and Methods: Following transfection of exon 17 to those with KIT (78% vs. 81%, P ¼ 0.905) but higher þ (E17) and exon 8 (E8) mutations into HEK293 and Ba/F3 relapse rates (RR ¼ 43% vs. 21%; P ¼ 0.005). E17 KIT À cells, KIT phosphorylation, cytokine-independent growth, outcomes were inferior to KIT patients [disease-free survival andresponsetotyrosinekinaseinhibitors(TKI)wereeval- (DFS), 51% vs. 73%, P ¼ 0.027; RR ¼ 21% vs. 46%, P ¼ uated. Clinical outcomes of patients treated on COG 0.007)], although gemtuzumab ozogamicin abrogated this AAML0531 (NCT01407757), a phase III study of gemtuzu- negative prognostic impact.
    [Show full text]