| 词条 | Pacritinib |
| 释义 |
| IUPAC_name = (16E)-11-[2-(1-Pyrrolidinyl)ethoxy]-14,19-dioxa-5,7,26-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene | image = Pacritinib skeletal.svg | width = 230 | alt = | caption = | tradename = | Drugs.com = | MedlinePlus = | pregnancy_AU = | pregnancy_US = | pregnancy_category= | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = Investigational | routes_of_administration = Oral | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number = 937272-79-2 | ATCvet = | ATC_prefix = None | ATC_suffix = | PubChem = 46216796 | DrugBank = | ChemSpiderID = 28518965 | ChEMBL = 2035187 | synonyms = SB1518 | C=28 | H=32 | N=4 | O=3 | molecular_weight = 472.58 g/mol | smiles = c1cc2cc(c1)-c3ccnc(n3)Nc4ccc(c(c4)COC/C=C/COC2)OCCN5CCCC5 | StdInChI=1S/C28H32N4O3/c1-2-13-32(12-1)14-17-35-27-9-8-25-19-24(27)21-34-16-4-3-15-33-20-22-6-5-7-23(18-22)26-10-11-29-28(30-25)31-26/h3-11,18-19H,1-2,12-17,20-21H2,(H,29,30,31)/b4-3+ | StdInChIKey = HWXVIOGONBBTBY-ONEGZZNKSA-N }}Pacritinib (INN[1]) is a macrocyclic Janus kinase inhibitor that is being developed for the treatment of myelofibrosis. It mainly inhibits Janus kinase 2 (JAK2) and Fms-like tyrosine kinase 3 (FLT3). The drug was in Phase III clinical trials {{as of|2013|lc=y}}.[2] The drug was discovered in Singapore at the labs of S*BIO Pte Ltd. It is a potent JAK2 inhibitor with activity of IC50 = 23 nM for the JAK2WT variant and 19 nM for JAK2V617F with very good selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively).[3][4] The drug was acquired by Cell Therapeutics, Inc. (CTI) and Baxter International and could effectively address an unmet medical need for patients living with myelofibrosis who face treatment-emergent thrombocytopenia on marketed JAK inhibitors.[5] When Shire Pharmaceuticals purchased Baxalta, a spin-off of Baxter Pharmaceuticals, they halted the development of the drug and ended their partnership with CTI.[6][7] The drug was given fast-track status in 2014.[8] In 2016, the FDA placed a full clinical hold on pacritinib due to concerns about increased mortality in patients receiving the drug in the "PERSIST-2" trial.[9] The clinical hold was lifted in January 2017.[10] References1. ^{{cite journal|url=http://apps.who.int/iris/bitstream/10665/74579/1/24_4_2010_INN104.pdf|journal=WHO Drug Information|volume=24|issue=4|year=2010|title=International Nonproprietary Names for Pharmaceutical Substances (INN) List 104|page=386}} {{Extracellular chemotherapeutic agents}}{{Cytokine receptor modulators}}{{antineoplastic-drug-stub}}2. ^{{cite journal|url=http://www.pharmazeutische-zeitung.de/index.php?id=46539|title=JAK-Inhibitoren: Neue Wirkstoffe für viele Indikationen|language=German|journal=Pharmazeutische Zeitung|issue=21|year=2013}} 3. ^{{Cite journal | doi = 10.1021/jm200326p| pmid = 21604762| title = Discovery of the Macrocycle 11-(2-Pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3 (JAK2/FLT3) Inhibitor for the Treatment of Myelofibrosis and Lymphoma| journal = Journal of Medicinal Chemistry| volume = 54| issue = 13| pages = 4638–58| year = 2011| last1 = William | first1 = A. D. | last2 = Lee | first2 = A. C. -H. | last3 = Blanchard | first3 = S. P. | last4 = Poulsen | first4 = A. | last5 = Teo | first5 = E. L. | last6 = Nagaraj | first6 = H. | last7 = Tan | first7 = E. | last8 = Chen | first8 = D. | last9 = Williams | first9 = M. | last10 = Sun | first10 = E. T. | last11 = Goh | first11 = K. C. | last12 = Ong | first12 = W. C. | last13 = Goh | first13 = S. K. | last14 = Hart | first14 = S. | last15 = Jayaraman | first15 = R. | last16 = Pasha | first16 = M. K. | last17 = Ethirajulu | first17 = K. | last18 = Wood | first18 = J. M. | last19 = Dymock | first19 = B. W. }} 4. ^{{Cite journal | doi = 10.1007/s10822-012-9572-z| pmid = 22527961| title = Structure-based design of oxygen-linked macrocyclic kinase inhibitors: Discovery of SB1518 and SB1578, potent inhibitors of Janus kinase 2 (JAK2) and Fms-like tyrosine kinase-3 (FLT3)| journal = Journal of Computer-Aided Molecular Design| volume = 26| issue = 4| pages = 437–50| year = 2012| last1 = Poulsen | first1 = A. | last2 = William | first2 = A. | last3 = Blanchard | first3 = S. P. | last4 = Lee | first4 = A. | last5 = Nagaraj | first5 = H. | last6 = Wang | first6 = H. | last7 = Teo | first7 = E. | last8 = Tan | first8 = E. | last9 = Goh | first9 = K. C. | last10 = Dymock | first10 = B. }} 5. ^http://www.pmlive.com/pharma_news/baxter_licenses_cancer_drug_from_cti_in_$172m_deal_519143 6. ^http://www.ctibiopharma.com/pipeline/pacritinib/ 7. ^http://www.in-pharmatechnologist.com/Regulatory-Safety/Shire-ends-pacritinib-development-deal-with-CTI-post-Baxalta-merger 8. ^http://www.fiercebiotech.com/biotech/struggling-cti-reveals-new-pacritinib-data-misses-a-primary-endpoint 9. ^http://www.streetinsider.com/Corporate+News/CTI+BioPharmas+(CTIC)+Pacritinib+Placed+on+Full+Clinical+Hold%3B+NDA+Withdrawn/11297746.html 10. ^{{cite web|title=CTI BioPharma Announces Removal Of Full Clinical Hold On Pacritinib|url=http://www.prnewswire.com/news-releases/cti-biopharma-announces-removal-of-full-clinical-hold-on-pacritinib-300386115.html|website=PR Newswire|accessdate=18 April 2017}} 4 : Pyrrolidines|Ethers|Experimental cancer drugs|Non-receptor tyrosine kinase inhibitors |
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