Alvocidib - Alvocidib

Alvocidib
Flavopiridol.svg
Alvocidib ball-and-stick.png
Ismlar
IUPAC nomi
2- (2-xlorofenil) -5,7-dihidroksi-8 - [(3S, 4R) -3-gidroksi-1-metil-4-piperidinil] -4-xromenon
Boshqa ismlar
Flavopiridol, HMR 1275, L-868275
Identifikatorlar
3D model (JSmol )
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
MeSHFlavopiridol
UNII
Xususiyatlari
C21H20ClNO5
Molyar massa401.8402
Boshqacha ko'rsatilmagan hollar bundan mustasno, ulardagi materiallar uchun ma'lumotlar berilgan standart holat (25 ° C [77 ° F], 100 kPa da).
☒N tasdiqlang (nima bu tekshirishY☒N ?)
Infobox ma'lumotnomalari

Alvocidib (KARVONSAROY; shuningdek, nomi bilan tanilgan Flavopiridol) a flavonoid alkaloid CDK9 kinaz inhibitori davolash uchun klinik rivojlanish ostida o'tkir miyeloid leykemiya, tomonidan Tolero Pharmaceuticals, Inc. Davolash uchun ham o'rganilgan artrit[1] va aterosklerotik blyashka shakllanish[2] Flavopiridolning maqsadi ijobiy transkripsiyaning uzayish omilidir P-TEFb.[3][4] Flavopiridol bilan hujayralarni davolash P-TEFb inhibisyoniga va yo'qotilishiga olib keladi mRNA ishlab chiqarish.[5][6]

Murakkab tabiiy mahsulotning sintetik analogidir rohitukin dastlab olingan Amoora rohituka [sin. Aphanamixis polystachya ] va undan keyin Dysoxylum binectariferum.[7][8]

Yetim dori

Tolero farmatsevtika Inc FDA tomonidan berilganligini e'lon qildi yetim dori Alvocidib, uning siklinga bog'liq kinaz kichik molekula inhibitori, bemorlarni davolash uchun belgilanishi o'tkir miyeloid leykemiya.[9]

Adabiyotlar

  1. ^ Sekine C, Sugihara T, Miyake S, Hirai H, Yoshida M, Miyasaka N, Kohsaka H (2008). "Romatoid artritning hayvonot modellarini kichik molekulali siklinga bog'liq kinaz inhibitörleri bilan muvaffaqiyatli davolash". J. Immunol. 180 (3): 1954–61. doi:10.4049 / jimmunol.180.3.1954. PMID  18209094.
  2. ^ Ruef J, Meshel AS, Xu Z, Horaist C, Ballinger CA, Tompson LJ, Subbarao VD, Dyumont JA, Patterson S (1999). "Flavopiridol in vitro va neointimal shakllanishda silliq mushak hujayralari ko'payishini inhibe qiladi. Sichqonchada karotid shikastlangandan so'ng in vivo jonli". Sirkulyatsiya. 100 (6): 659–65. doi:10.1161 / 01.cir.100.6.659. PMID  10441105.
  3. ^ Chao SH, Fujinaga K, Marion JE, Taube R, Sausvill EA, Senderowicz AM, Peterlin BM, Narx DH (2000). "Flavopiridol P-TEFb ni inhibe qiladi va OIV-1 replikatsiyasini bloklaydi". J. Biol. Kimyoviy. 275 (37): 28345–8. doi:10.1074 / jbc.C000446200. PMID  10906320.
  4. ^ Chao SH, Narx DH (2001). "Flavopiridol P-TEFb ni inaktiv qiladi va in Vivo jonli ravishda RNK polimeraza II transkripsiyasini bloklaydi". J. Biol. Kimyoviy. 276 (34): 31793–9. doi:10.1074 / jbc.M102306200. PMID  11431468.
  5. ^ Cheng B, Li T, Rahl PB, Adamson TE, Loudas NB, Guo J, Varzavand K, Cooper JJ, Xu X, Gnatt A, Young RA, Narx DH (2012). "Gdown1 ning inson genlariga asoslangan RNK polimeraza II bilan funktsional assotsiatsiyasi". Mol. Hujayra. 45 (1): 38–50. doi:10.1016 / j.molcel.2011.10.022. PMC  3259526. PMID  22244331.
  6. ^ Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, Sharp PA, Young RA (2010). "c-Myc transkripsiyaviy pauza chiqarilishini tartibga soladi". Hujayra. 141 (3): 432–45. doi:10.1016 / j.cell.2010.03.030. PMC  2864022. PMID  20434984.
  7. ^ Harmon, AD; Vayss, U; Silverton, QK (1979). "Rohitukinning tuzilishi, Amora rohitukaning asosiy alkaloidi (syn.Aphanamixis polystachya) (Meliaceae)". Tetraedr Lett. 20 (1): 721–724. doi:10.1016 / S0040-4039 (01) 93556-7.
  8. ^ Lakdawala, AD; Shirole, MV; Mandrekar, SS; Dohadwalla, AN (1988). "Rohitukinning immunofarmakologik salohiyati: Dysoxylum binectariferum o'simlikidan ajratilgan yangi birikma". Asia Pac J Pharmcol. 3 (1): 91–98.
  9. ^ http://www.healio.com/hematology-oncology/hematologic-malignancies/news/online/%7B74c6a69e-4529-400d-98e9-d5ee6c602122%7D/fda-grants-orphan-drug-status-to-alvocidib-for -aml