Z BioInf
(→Niskocząsteczkowe inhibitory domeny kinazowej JAK2) |
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| (Nie pokazano 91 pośrednich wersji utworzonych przez tego samego użytkownika) | |||
| Linia 1: | Linia 1: | ||
| − | == | + | ==Small molecule inhibitors of the tyrosine kinase JAK2== |
{|class="wikitable center" style="text-align:center; font-size:100%; border:1px" | {|class="wikitable center" style="text-align:center; font-size:100%; border:1px" | ||
| − | ! rowspan=2| | + | ! rowspan=2|Nb |
| − | ! rowspan=2|inhibitor<br>( | + | ! rowspan=2|inhibitor<br>(other kinase targets) |
| − | ! rowspan=2| | + | ! rowspan=2|chemical class |
| − | ! test | + | ! enzymatic test |
| − | ! colspan=2|test | + | ! colspan=2|cell test |
| − | ! rowspan=2| | + | ! rowspan=2| references |
|- | |- | ||
!scope="row"|IC<sub>50</sub> (µM) | !scope="row"|IC<sub>50</sub> (µM) | ||
| − | !scope="row"| | + | !scope="row"| cell line |
!scope="row"|GI<sub>50</sub> (µM) | !scope="row"|GI<sub>50</sub> (µM) | ||
|- | |- | ||
|1 | |1 | ||
| − | !scope="row" style="background-color: | + | !scope="row" style="background-color:LemonChiffon" |AG490<br>(EGFR, PDGFR) |
|tyrphostin | |tyrphostin | ||
|36.4<br>48<br>145.3 | |36.4<br>48<br>145.3 | ||
| − | |B-precursor (KOCL-33,-45,-50,-69,KOPN-30bi,-55bi,-57bi,-72bi,KOPN-32,-62,-84,NALM 6)<br>T-precursor (KOPT-K1,-5,-11,Jurkat)<br>Ba/F3: | + | |B-precursor (KOCL-33,-45,<br>-50,-69,KOPN-30bi,-55bi,<br>-57bi,-72bi,KOPN-32,-62,<br>-84,NALM 6)<br>T-precursor (KOPT-K1,-5,<br>-11,Jurkat)<br>Ba/F3:JAK2<sup>V617F</sup><br>HEL (JAK2<sup>V617F</sup>)<br>SET-2 (JAK2<sup>V617F/wt</sup>)<br>XG-1<br>XG-2<br>U266<br>MDAH2774<br>Caov-3<br>MDA-MB-468 |
| − | |<br>-<br> | + | |<nowiki>-</nowiki><br><br><br><br>-<br><br>1.0<br>>20.0<br>>20.0<br>14.8<br>12.9<br>26.0<br>-<br>-<br>- |
| − | |Gazit et al. 1989 | + | |[http://dx.doi.org/10.1021/jm00130a020 Gazit et al. 1989]<br>[http://dx.doi.org/10.1021/jm00110a022 Gazit et al. 1991]<br>[http://dx.doi.org/10.1038/379645a0 Meydan et al. 1996]<br>[http://dx.doi.org/10.1046/j.1365-2141.2000.02127.x Vos et al. 2000]<br>[http://www.nature.com/leu/journal/v15/n11/full/2402260a.html Miyamoto et al. 2001]<br>[http://www.nature.com/onc/journal/v20/n55/full/1204990a.html Burke et al. 2001]<br>[http://dx.doi.org/10.1023/A%3A1016186907376 Duhé et al. 2002]<br>[http://www.sciencedirect.com/science/article/pii/S0968089610000829 Reddy et al. 2010]<br>[http://gan.sagepub.com/content/1/4/331.abstract Jatiani et al. 2010] |
| − | | | + | |- |
|2 | |2 | ||
| − | |LS104 | + | !scope="row" style="background-color:LemonChiffon" |LS104<br>(BCR-ABL) |
| − | (BCR-ABL) | ||
|tyrphostin | |tyrphostin | ||
| − | |2.52 | + | |2.52<br>0.1-0.6 |
| − | 0.1-0.6 | + | |Ba/F3:EpoR,JAK2<sup>V617F</sup><br>Ba/F3:EpoR,JAK2<sup>wt</sup><br>HEL |
| − | |Ba/F3:EpoR, | + | |1.5<br>10.0 |
| − | Ba/F3:EpoR, | + | |[http://bloodjournal.hematologylibrary.org/content/102/12/4153.abstract Grunberger et al. 2003]<br>[http://mct.aacrjournals.org/content/7/5/1176.abstract Lipka et al. 2008] |
| − | HEL | + | |- |
| − | |1.5 | ||
| − | 10.0 | ||
| − | |Grunberger et al. 2003 | ||
| − | Lipka et al. 2008 | ||
| − | | | ||
|3 | |3 | ||
| − | |WP1066 | + | !scope="row" style="background-color:LemonChiffon" |WP1066 |
|tyrphostin | |tyrphostin | ||
| + | |<nowiki>-</nowiki> | ||
| + | |HEL | ||
| + | |2.3 | ||
| + | |[http://clincancerres.aacrjournals.org/content/14/3/788.abstract Verstovsek et al. 2008] | ||
|- | |- | ||
| − | |||
| − | |||
| − | |||
| − | |||
|4 | |4 | ||
| − | |ON044580 | + | !scope="row" style="background-color:LemonChiffon" |ON044580<br>(BCR-ABL) |
| − | (BCR-ABL) | + | |α-benzoyl styryl benzyl sulfide |
| − | |& | + | |0.9-1.2<br>4.2 |
| − | |0.9-1.2 | + | |Ba/F3:JAK2<sup>V617F</sup><br>HEL<br>SET-2 |
| − | 4.2 | + | |0.25<br>0.90<br>3.00 |
| − | |Ba/F3: | + | |[http://www.sciencedirect.com/science/article/pii/S0968089610000829 Reddy et al. 2010]<br>[http://gan.sagepub.com/content/1/4/331.abstract Jatiani et al. 2010]<br>[http://gan.sagepub.com/content/1/4/346.abstract Samanta et al. 2010] |
| − | HEL | + | |- |
| − | SET-2 | ||
| − | |0.25 | ||
| − | 0.90 | ||
| − | 3.00 | ||
| − | |Reddy et al. 2010 | ||
| − | Jatiani et al. 2010 | ||
| − | Samanta et al. 2010 | ||
| − | | | ||
|5 | |5 | ||
| − | |CEP701 | + | !scope="row" style="background-color:LemonChiffon" |lestaurtinib<br>(CEP701)<br>(FLT3,JAK3) |
| − | (FLT3,JAK3) | ||
|indolocarbazole | |indolocarbazole | ||
|0.001 | |0.001 | ||
|HEL | |HEL | ||
|0.03-0.10 | |0.03-0.10 | ||
| − | |Hexner et al. 2008 | + | |[http://bloodjournal.hematologylibrary.org/content/111/12/5663.abstract Hexner et al. 2008]<br>[http://bloodjournal.hematologylibrary.org/content/115/6/1131.abstract Santos et al. 2010] |
| − | Santos et al. 2010 | + | |- |
| − | | | ||
|6 | |6 | ||
| − | | | + | !scope="row" style="background-color:LemonChiffon" |Gö6976<br>(JAK3, FLT3, PKCα,β1) |
| − | (JAK3, | ||
| − | FLT3, | ||
| − | |||
|indolocarbazole | |indolocarbazole | ||
|0.13 | |0.13 | ||
| − | |32D | + | |32D<br>32D:TEL-JAK2<br>FDCP1<br>TF-1<br>Mo7E<br>HEL |
| − | 32D:TEL-JAK2 | + | |0.093<br>0.242<br>-<br>-<br>-<br>- |
| − | FDCP1 | + | |[http://dx.doi.org/10.1111/j.1365-2141.2006.06291.x Grandage et al. 2006] |
| − | TF-1 | + | |- |
| − | Mo7E | ||
| − | HEL | ||
| − | |0.093 | ||
| − | 0.242 | ||
| − | - | ||
| − | - | ||
| − | - | ||
| − | - | ||
| − | |Grandage et al. 2006 | ||
| − | | | ||
|7 | |7 | ||
| − | |TG02 | + | !scope="row" style="background-color:LemonChiffon" |TG02<br>(CDKs, TYK2, FLT3, TYRO3, ERK5, p38δ, Fms, Lck, Fyn, JAK1) |
| − | (CDKs, | ||
| − | FLT3) | ||
|pyrimidine | |pyrimidine | ||
| − | |-HEL | + | |<nowiki>-</nowiki> |
| − | SET-2 | + | |HEL<br>SET-2<br>Ba/F3:JAK2<sup>wt</sup><br>Ba/F3:JAK2<sup>V617F</sup><br>Karpas-1106P<br>32D |
| − | Ba/F3: | + | |0.202<br>0.231<br>0.156<br>0.099<br>0.068<br>0.098 |
| − | Ba/F3: | + | |[http://dx.doi.org/10.1038/leu.2011.218 Goh et al. 2012]<br>[http://dx.doi.org/10.1111/bjh.12018 Pallis et al. 2012] |
| − | Karpas-1106P | + | |- |
| − | 32D | ||
| − | |0.202 | ||
| − | 0.231 | ||
| − | 0.156 | ||
| − | 0.099 | ||
| − | 0.068 | ||
| − | 0.098 | ||
| − | |Goh et al. | ||
| − | | | ||
|8 | |8 | ||
| − | |TG101209 | + | !scope="row" style="background-color:LemonChiffon" |TG101209<br>(FLT3, RET, JAK3) |
| − | (FLT3, | ||
| − | RET, | ||
| − | JAK3) | ||
|pyrimidine | |pyrimidine | ||
|0.006 | |0.006 | ||
| − | |Ba/F3: | + | |Ba/F3:JAK2<sup>V617F</sup><br>HEL<br>multiple myeloma cell lines (RPMI8226, MM1S, OPM2, NCI-H929, Dox40, MM1R, LR5) |
| − | HEL | + | |0.2<br>2-5<br>- |
| − | + | |[http://dx.doi.org/10.1038/sj.leu.2404750 Pardanani et al. 2007]<br>[http://bloodjournal.hematologylibrary.org/content/114/24/5024.abstract Wang and Fiskus et al. 2009]<br>[http://dx.doi.org/10.1002/ajh.21785 Ramakrishnan et al. 2010] | |
| − | |0.2 | ||
| − | 2-5 | ||
|- | |- | ||
| − | |||
| − | |||
| − | |||
| − | |||
|9 | |9 | ||
| − | |TG101348 | + | !scope="row" style="background-color:LemonChiffon" |TG101348<br>(FLT3, RET, JAK1, JAK3, TYK2) |
| − | (FLT3,RET,JAK1, | ||
| − | JAK3,TYK2) | ||
|pyrimidine | |pyrimidine | ||
|0.003 | |0.003 | ||
| − | |Ba/F3: | + | |Ba/F3:JAK2<sup>V617F</sup><br>HEL |
| − | HEL | + | |0.270<br>0.305 |
| − | |0.270 | + | |[http://www.sciencedirect.com/science/article/pii/S1535610808000457 Wernig et al. 2008]<br>[http://abstracts.hematologylibrary.org/cgi/content/abstract/ashmtg;114/22/755 Pardanani et al. 2009]<br>[http://jco.ascopubs.org/content/29/7/789.abstract Pardanani et al. 2011] |
| − | 0.305 | + | |- |
| − | |Wernig et al. 2008 | ||
| − | |||
| − | Pardanani et al. 2011 | ||
| − | | | ||
|10 | |10 | ||
| − | |R723 | + | !scope="row" style="background-color:LemonChiffon" |R723<br>(JAK3, TYK2, FLT3, PRKD2, TBK1, SYK, PAK4, DAPK3, PRKD1, MYLK2, PRKCN, STK22D, IKBKE) |
| − | (JAK3,TYK2,FLT3, | ||
| − | PRKD2,TBK1,SYK, | ||
| − | PAK4,DAPK3,PRKD1,MYLK2,PRKCN, | ||
| − | STK22D,IKBKE) | ||
|pyrimidine | |pyrimidine | ||
|0.002 | |0.002 | ||
| − | |Ba/F3: | + | |Ba/F3:JAK2<sup>V617F</sup> |
|0.13-0.20 | |0.13-0.20 | ||
| − | |Shide et al. 2009 | + | |[https://ash.confex.com/ash/2009/webprogram/Paper18988.html Shide et al. 2009]<br>[http://bloodjournal.hematologylibrary.org/content/117/25/6866.abstract Shide et al. 2011] |
| − | Shide et al. 2011 | + | |- |
| − | | | ||
|11 | |11 | ||
| − | |INCB018424 | + | !scope="row" style="background-color:LemonChiffon" |INCB018424<br>(JAK1, JAK3, TYK2) |
| − | (JAK1,JAK3,TYK2) | ||
|pyrrolopyrimidine | |pyrrolopyrimidine | ||
|0.0045 | |0.0045 | ||
| − | - | + | |<nowiki>-</nowiki> |
| − | - | + | |<nowiki>-</nowiki> |
| − | |Verstovsek et al. 2008 | + | |[http://abstracts.hematologylibrary.org/cgi/content/abstract/ashmtg;110/11/3538 Fridman et al. 2007]<br>[http://abstracts.hematologylibrary.org/cgi/content/abstract/ashmtg;110/11/558 Verstovsek et al. 2007]<br>[https://ash.confex.com/ash/2008/webprogram/Paper8625.html Verstovsek et al. 2008]<br>[http://www.nejm.org/doi/full/10.1056/NEJMoa1002028 Verstovsek et al. 2010]<br>[http://bloodjournal.hematologylibrary.org/content/115/15/3109.abstract Quintás-Cardama et al. 2010]<br>[http://dx.doi.org/10.1002/cncr.26129 Mesa et al. 2011] |
| − | Mesa | + | |- |
| − | | | ||
|12 | |12 | ||
| − | |INCB16562 | + | !scope="row" style="background-color:LemonChiffon" |INCB16562<br>(JAK1, JAK3) |
| − | (JAK1,JAK3) | ||
|pyrrolopyrimidine | |pyrrolopyrimidine | ||
|0.0003 | |0.0003 | ||
| − | |Ba/F3: | + | |Ba/F3:JAK2<sup>V617F</sup><br>Ba/F3:JAK2<sup>K539L</sup><br>Ba/F3:MPL<sup>W515L</sup><br>Ba/F3:TEL-JAK2<br>SET-2<br>UKE-1 |
| − | Ba/F3: | + | |0.177<br>0.406<br>0.600<br>0.168<br>0.046<br>0.573 |
| − | Ba/F3: | + | |[http://bloodjournal.hematologylibrary.org/content/115/14/2919.abstract Koppikar et al. 2010] |
| − | Ba/F3:TEL-JAK2 | + | |- |
| − | SET-2 | ||
| − | UKE-1 | ||
| − | |0.177 | ||
| − | 0.406 | ||
| − | 0.600 | ||
| − | 0.168 | ||
| − | 0.046 | ||
| − | 0.573 | ||
| − | |Koppikar et al. 2010 | ||
| − | | | ||
|13 | |13 | ||
| − | |CP690550 | + | !scope="row" style="background-color:LemonChiffon" |CP690550<br>(JAK1, JAK3, TYK2) |
| − | (JAK1, | ||
| − | JAK3, | ||
| − | TYK2) | ||
|pyrrolopyrimidine | |pyrrolopyrimidine | ||
| − | |0.0041 | + | |0.0041<br>0.011<br>0.012<br>0.020 |
| − | 0.011 | + | |FDCP-EpoR,JAK2<sup>wt</sup><br>FDCP-EpoR,JAK2<sup>V617F</sup> |
| − | 0.012 | + | |2.1<br>0.25 |
| − | 0.020 | + | |[http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=11414503&lang=pl&site=eds-live&scope=site Changelian et al. 2003]<br>[http://www.sciencedirect.com/science/article/pii/S0960894X06009152 Chen et al. 2006]<br>[http://www.sciencedirect.com/science/article/pii/S0960894X06014053 Clark et al. 2007]<br>[http://dx.doi.org/10.1111/j.1349-7006.2008.00817.x Manshouri et al. 2008]<br>[http://www.journal-inflammation.com/content/7/1/41 Meyer et al. 2010]<br>[http://dx.doi.org/10.1021/jm101157q Thoma et al. 2011] |
| − | |FDCP-EpoR, | + | |- |
| − | FDCP-EpoR, | ||
| − | |2.1 | ||
| − | 0.25 | ||
| − | |Changelian et al. 2003 | ||
| − | Chen et al. 2006 | ||
| − | Clark et al. 2007 | ||
| − | Manshouri et al. 2008 | ||
| − | Meyer et al. 2010 | ||
| − | Thoma et al. 2011 | ||
| − | | | ||
|14 | |14 | ||
| − | |AZD1480 | + | !scope="row" style="background-color:LemonChiffon" |AZD1480<br>(JAK1, JAK3, TRKA, AuroraA, FLT4, FGFR1, ARK5) |
| − | (JAK1,JAK3,TRKA, | + | |pyrazolopyrimidine |
| − | AuroraA,FLT4,FGFR1,ARK5) | + | |0.0004<br>|0.003 |
| − | pyrazolopyrimidine | + | |Ba/F3:TEL-JAK2<br>SET-2<br>UKE1<br>HEL |
| − | |0.0004 | + | |0.06<br>0.016<br>0.054<br>0.39 |
| − | |0.003 | + | |[http://www.cell.com/cancer-cell/abstract/S1535-6108(09)00384-5 Hedvat et al. 2009]<br>[http://dx.doi.org/10.1021/jm1011319 Ioannidis et al. 2011] |
| − | |Ba/F3:TEL-JAK2 | + | |- |
| − | SET-2 | ||
| − | UKE1 | ||
| − | HEL | ||
| − | |0.06 | ||
| − | 0.016 | ||
| − | 0.054 | ||
| − | 0.39 | ||
| − | |Hedvat et al. 2009 | ||
| − | Ioannidis et al. 2011 | ||
| − | | | ||
|15 | |15 | ||
| − | |CYT387 | + | !scope="row" style="background-color:LemonChiffon" |CYT387<br>(JAK1, TYK2, CDK2/cyclinA, JNK1, PRKCN, PRKD1, ROCK2, TBK1) |
| − | (JAK1,TYK2, | ||
| − | CDK2/cyclinA, | ||
| − | JNK1,PRKCN, | ||
| − | PRKD1,ROCK2,TBK1) | ||
|aminopyrimidine | |aminopyrimidine | ||
|0.018 | |0.018 | ||
| − | |Ba/F3:EpoR, | + | |Ba/F3:EpoR,JAK2<sup>V617F</sup><br>32D:EpoR,JAK2<sup>V617F</sup><br>HEL<br>TF-1<br>U266<br>CHRF-288-11:JAK2<sup>T875N</sup><br>Ba/F3:TEL-JAK2 |
| − | 32D:EpoR, | + | |0.5<br>1.5<br>1.5<br>1.25<br>0.75<br>0.001<br>0.724 |
| − | HEL | + | |[http://dx.doi.org/10.1038/leu.2009.50 Pardanani et al. 2009]<br>[http://bloodjournal.hematologylibrary.org/content/115/25/5232.abstract Tyner et al. 2010] |
| − | TF-1 | + | |- |
| − | U266 | ||
| − | CHRF-288-11: | ||
| − | Ba/F3:TEL-JAK2 | ||
| − | |0.5 | ||
| − | 1.5 | ||
| − | 1.5 | ||
| − | 1.25 | ||
| − | 0.75 | ||
| − | 0.001 | ||
| − | 0.724 | ||
| − | |Pardanani et al. 2009 | ||
| − | Tyner et al. 2010 | ||
| − | | | ||
|16 | |16 | ||
| − | |SGI1252 | + | !scope="row" style="background-color:LemonChiffon" |SGI1252<br>(JAK1, JAK3, TYK2, YES, FLT3, ABL, SRC, LCK) |
| − | (JAK1,JAK3,TYK2, | ||
| − | YES,FLT3,ABL,SRC, | ||
| − | LCK) | ||
|diaminopyrimidine | |diaminopyrimidine | ||
| − | |0.002 | + | |0.0054<br>0.002<br>0.0197 |
| − | 0.0197 | + | |FDCP-EpoR,JAK2<sup>wt</sup><br>FDCP-EpoR,JAK2<sup>V617F</sup><br>HEL<br>SET-2<br>UKE-1 |
| − | |FDCP-EpoR, | + | |0.074<br>0.110<br>0.441<br>0.055<br>0.089 |
| − | FDCP-EpoR, | + | |[http://linkinghub.elsevier.com/retrieve/pii/S1359634908725059?showall=true Olsen et al. 2008]<br>[https://ash.confex.com/ash/2008/webprogram/Paper10062.html Riaz Ahmed et al. 2008]<br>[http://linkinghub.elsevier.com/retrieve/pii/S0301472X10004947?showall=true Riaz Ahmed et al. 2011] |
| − | HEL | + | |- |
| − | SET-2 | ||
| − | UKE-1 | ||
| − | |0.074 | ||
| − | 0.110 | ||
| − | 0.441 | ||
| − | 0.055 | ||
| − | 0.089 | ||
| − | |Olsen et al. 2008 | ||
| − | Riaz Ahmed et al. 2011 | ||
| − | | | ||
|17 | |17 | ||
| − | |SB1518 | + | !scope="row" style="background-color:LemonChiffon" |SB1518<br>(FLT3, JAK1, JAK3, TYK2) |
| − | (FLT3,JAK1, | + | |aminopyrimidine macrocycle |
| − | JAK3,TYK2) | + | |0.023<br>0.019 |
| − | aminopyrimidine macrocycle | + | |Ba/F3:JAK2<sup>V617F</sup><br>HEL<br>SET-2<br>Karpas-1106P<br>U266 |
| − | |0.023 | + | |0.16<br>1.726<br>0.217<br>0.348<br>1.350 |
| − | 0.019 | + | |[http://dx.doi.org/10.1038/leu.2011.148 Hart et al. 2011]<br>[http://pubs.acs.org/doi/abs/10.1021/jm200326p William et al. 2011] |
| − | |Ba/F3: | + | |- |
| − | HEL | ||
| − | SET-2 | ||
| − | Karpas-1106P | ||
| − | U266 | ||
| − | |0.16 | ||
| − | 1.726 | ||
| − | 0.217 | ||
| − | 0.348 | ||
| − | 1.350 | ||
| − | |Hart et al. 2011 | ||
| − | William et al. 2011 | ||
| − | | | ||
|18 | |18 | ||
| − | |Z3 | + | !scope="row" style="background-color:LemonChiffon" |"38"<br>(JAK1, TYK2, JAK3, MEKK2, MEKK3) |
| + | |8-oxo-pyridopyrimidine | ||
| + | |0.001 | ||
| + | |TF-1-EPO (IC<sub>50</sub>) | ||
| + | |0.115 | ||
| + | |[http://www.sciencedirect.com/science/article/pii/S0960894X13010226 Labadie et al. 2013] | ||
| + | |- | ||
| + | |19 | ||
| + | !scope="row" style="background-color:LemonChiffon" |Z3 | ||
|pyridine | |pyridine | ||
| − | |15.0 | + | |15.0<br>28.0 |
| − | 28.0 | ||
|HEL | |HEL | ||
| − | |Sayyah et al. 2008 | + | |<nowiki>-</nowiki> |
| − | | | + | |[http://mct.aacrjournals.org/content/7/8/2308.abstract Sayyah et al. 2008] |
| − | | | + | |- |
| − | |25(JAK1,GAK,YSK4) | + | |20 |
| + | !scope="row" style="background-color:LemonChiffon" |"25"<br>(JAK1, GAK, YSK4) | ||
|thienopyridine | |thienopyridine | ||
|0.002 | |0.002 | ||
| − | |Ba/F3:TEL-JAK2 ( | + | |Ba/F3:TEL-JAK2 (IC<sub>50</sub>) |
|1.62 | |1.62 | ||
| − | |Schenkel et al. 2011 | + | |[http://dx.doi.org/10.1021/jm200911r Schenkel et al. 2011] |
| − | | | + | |- |
| − | | | + | |21 |
| − | |65 | + | !scope="row" style="background-color:LemonChiffon" |"65"<br>(JAK1, cSRC, TRKA, ACK1, FMS, FYN, FLT3, HCK, RET, BMX, LYN, FGR, LCK, ARK5, BTK, YES, PTK5, TRKB, CaMKIIδ,γ, PRK2, ARG, MLK1, ALK) |
| − | (JAK1,cSRC,TRKA, | ||
| − | ACK1,FMS,FYN,FLT3,HCK,RET,BMX,LYN, | ||
| − | FGR,LCK,ARK5,BTK,YES,PTK5,TRKB, | ||
| − | |||
|pyridoindolcarboxamide | |pyridoindolcarboxamide | ||
| − | 0.0008 | + | |0.0008 |
| − | irf1-bla HEL ( | + | |irf1-bla HEL (IC<sub>50</sub>) |
| − | 0.025 | + | |0.025 |
| − | Lim et al. 2011 | + | |[http://dx.doi.org/10.1021/jm200909u Lim et al. 2011] |
| − | + | |- | |
| − | AT9283 | + | |22 |
| − | (AuroraK,JAK3, FLT3,ABL) | + | !scope="row" style="background-color:LemonChiffon" |AT9283<br>(AuroraK, JAK3, FLT3, ABL) |
| − | pyrazole benzimidazole | + | |pyrazole benzimidazole |
| − | 0.0012 | + | |0.0012 |
| − | HEL ( | + | |HEL (JAK2<sup>V617F</sup>)<br>SET-2 (JAK2<sup>V617F/wt</sup>)<br>Ba/F3:ETV6-JAK2<br>Ba/F3-IL-3<br>TF-1-IL-3<br>CMK (JAK2<sup>A572V</sup>) |
| − | SET-2 ( | + | |0.110<br>0.057<br>0.016<br>0.017<br>0.040<br>0.026 |
| − | Ba/F3:ETV6-JAK2 | + | |[http://dx.doi.org/10.1021/jm800984v Howard et al. 2009]<br>[http://dx.doi.org/10.1111/j.1365-2141.2010.08175.x Dawson et al. 2010] |
| − | Ba/F3-IL-3 | + | |- |
| − | TF-1-IL-3 | + | |23 |
| − | CMK ( | + | !scope="row" style="background-color:LemonChiffon" |AZ960<br>(TRKA, AuroraA, ARK5, ALK, CaMKII, FLT4, FGFR1, LIMK1, BrSK2, FAK) |
| − | 0.110 | + | |pyrazole nicotinonitrile |
| − | 0.057 | + | |0.003 |
| − | 0.016 | + | |SET-2 (JAK2<sup>V617F/wt</sup>)<br>Ba/F3:TEL-JAK2<br>HTLV-1 infected T cells (MT-1, MT-2) |
| − | 0.017 | + | |0.033<br>0.025<br>- |
| − | 0.040 | + | |[http://www.jbc.org/content/283/47/32334.abstract Gozgit et al. 2008]<br>[http://mct.aacrjournals.org/content/9/12/3386.abstract Yang et al. 2010] |
| − | 0.026 | + | |- |
| − | Howard et al. 2009 | + | |24 |
| − | Dawson et al. 2010 | + | !scope="row" style="background-color:LemonChiffon" |CMP6<br>(JAK1, JAK3, TYK2) |
| − | + | |pyridone tetracycle | |
| − | AZ960 | + | |0.001 |
| − | (TRKA,AuroraA, | + | |CTLL-2<br>B9<br>U266<br>KMS11 |
| − | ARK5,ALK,CaMKII, | + | |0.052-0.1<br>0.25<br>-<br>- |
| − | FLT4,FGFR1,LIMK1, | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X02001063 Thompson et al. 2002]<br>[http://bloodjournal.hematologylibrary.org/content/107/1/176.abstract Lucet et al. 2006]<br>[http://cancerres.aacrjournals.org/content/66/19/9714.abstract Pedranzini et al. 2006] |
| − | BrSK2,FAK) | + | |- |
| − | pyrazole nicotinonitrile | + | |25 |
| − | 0.003 | + | !scope="row" style="background-color:LemonChiffon" |"13" |
| − | SET-2 ( | + | |sulfonamide aminoindazole |
| − | Ba/F3:TEL-JAK2 | + | |0.078 |
| − | HTLV-1 infected T cells (MT-1, MT-2) | + | |<nowiki>-</nowiki> |
| − | 0.033 | + | |<nowiki>-</nowiki> |
| − | 0.025 | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X08010007 Antonysamy et al. 2009] |
| − | - | + | |- |
| − | + | |26 | |
| − | Gozgit et al. 2008 | + | !scope="row" style="background-color:LemonChiffon" |comp 9<br>(JAK3, ALK, cKIT, GCK) |
| − | Yang et al. 2010 | + | |polycyclic azaindole |
| − | + | |0.001 | |
| − | CMP6 | + | |TF-1-GMCSF (IC<sub>50</sub>)<br>HT2-IL2 (IC<sub>50</sub>) |
| − | (JAK1, | + | |0.27<br>1.53 |
| − | JAK3, | + | |[http://dx.doi.org/10.1021/jm901383u Wang et al. 2009] |
| − | TYK2) | + | |- |
| − | pyridone tetracycle | + | |27 |
| − | 0.001 | + | !scope="row" style="background-color:LemonChiffon" |"15a" |
| − | CTLL-2 | + | |polycyclic azaindole |
| − | B9 | + | |0.0008 |
| − | U266 | + | |TF-1-GMCSF (IC<sub>50</sub>) |
| − | KMS11 | + | |0.16 |
| − | 0.052-0.1 | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X09015911 Wang et al. 2010] |
| − | 0.25 | + | |- |
| − | - | + | |28 |
| − | - | + | !scope="row" style="background-color:LemonChiffon" |"40"<br>(JAK3) |
| − | Thompson et al. 2002 | + | |aminopyrazolopyrimidine |
| − | Lucet et al. 2006 | + | |0.0002 |
| − | Pedranzini et al. | + | |TF-1-GMCSF (IC<sub>50</sub>)<br>HT2-IL2 (IC<sub>50</sub>) |
| − | + | |0.16<br>3.2 | |
| − | 13 | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X09014541 Ledeboer et al. 2009] |
| − | sulfonamide aminoindazole | + | |- |
| − | 0.078 | + | |29 |
| − | - | + | !scope="row" style="background-color:LemonChiffon" |"29"<br>(JAK1, JAK3) |
| − | - | + | |pyrrolotriazine aminopyrrazole |
| − | Antonysamy et al. 2009 | + | |0.0018 |
| − | + | |SET-2 | |
| − | comp 9 | + | |0.11 |
| − | (JAK3,ALK, | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X11000357 Harikrishnan et al. 2011] |
| − | cKIT,GCK) | + | |- |
| − | polycyclic azaindole | + | |30 |
| − | 0.001 | + | !scope="row" style="background-color:LemonChiffon" |atiprimod<br>(JAK3) |
| − | TF-1-GMCSF ( | + | |azaspirane |
| − | HT2-IL2 ( | + | |<nowiki>-</nowiki> |
| − | 0.27 | + | |FDCP-EpoR,JAK2<sup>wt</sup><br>FDCP-EpoR,JAK2<sup>V617F</sup><br>SET-2 |
| − | 1.53 | + | |0.69<br>0.42<br>0.53 |
| − | Wang et al. 2009 | + | |[http://bloodjournal.hematologylibrary.org/content/105/11/4470.abstract Hamasaki et al. 2005]<br>[http://dx.doi.org/10.1007/s10637-010-9429-z Quintás-Cardama et al. 2011] |
| − | + | |- | |
| − | 15a | + | |31 |
| − | polycyclic azaindole | + | !scope="row" style="background-color:LemonChiffon" |G6 |
| − | 0.0008 | + | |stilbenoid<br>(diaryleten) |
| − | TF-1-GMCSF ( | + | |0.060 |
| − | 0.16 | + | |Ba/F3:EpoR,JAK2<sup>V617F</sup><br>HEL |
| − | Wang et al. 2010 | + | |<nowiki>-</nowiki><br>4.0 |
| − | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X09006477 Kiss et al. 2009]<br>[http://www.jbc.org/content/285/41/31399.abstract Majumder et al. 2010]<br>[http://www.jbc.org/content/286/6/4280.abstract Kirabo et al. 2011] | |
| − | 40 | + | |- |
| − | (JAK3) | + | |32 |
| − | aminopyrazolopyrimidine | + | !scope="row" style="background-color:LemonChiffon" |NVP-BSK805<br>(JAK1, TYK2, ABL) |
| − | 0.0002 | + | |diarylquinoxaline |
| − | TF-1-GMCSF ( | + | |0.00048<br>0.00058<br>0.00056 |
| − | HT2-IL2 ( | + | |Ba/F3:JAK2<sup>V617F</sup><br>SET-2<br>MB-02<br>UKE-1<br>MUTZ-8 |
| − | 0.16 | + | |0.039<br>0.051<br>0.064<br>0.071<br>0.331 |
| − | 3.2 | + | |[http://mct.aacrjournals.org/content/9/7/1945.abstract Baffert et al. 2010] |
| − | Ledeboer et al. 2009 | + | |- |
| − | + | |33 | |
| − | 29 | + | !scope="row" style="background-color:LemonChiffon" |"26"<br>(ABL) |
| − | (JAK1,JAK3) | + | |diarylquinoxaline |
| − | pyrrolotriazine aminopyrrazole | + | |0.0073 |
| − | 0.0018 | + | |SET-2 |
| − | SET-2 | + | |0.088 |
| − | 0.11 | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X10002568 Pissot-Soldermann et al. 2010] |
| − | Harikrishnan et al. 2011 | + | |- |
| − | + | |34 | |
| − | atiprimod | + | !scope="row" style="background-color:LemonChiffon" |hexabromo cyclohexane |
| − | (JAK3) | + | |cyclohexane |
| − | azaspirane | + | |low µM |
| − | - | + | |γ-2A |
| − | FDCP-EpoR, | + | |<nowiki>-</nowiki> |
| − | FDCP-EpoR, | + | |[http://dx.doi.org/10.1021/jm049470k Sandberg et al. 2005] |
| − | SET-2 | + | |- |
| − | 0.69 | + | |35 |
| − | 0.42 | + | !scope="row" style="background-color:LemonChiffon" |XL019<br>(JAK1, JAK3, FLT3, PDGFRB, cKIT) |
| − | 0.53 | + | |arylaminopyrimidine |
| − | Hamasaki et al. 2005 | + | |0.002 |
| − | Quintás-Cardama et al. 2011 | + | |HEL |
| − | + | |<nowiki>-</nowiki> | |
| − | G6 | + | |[http://abstracts.hematologylibrary.org/cgi/content/abstract/ashmtg;112/11/2810 Paquette et al. 2008]<br>[http://abstracts.hematologylibrary.org/cgi/content/abstract/ashmtg;112/11/98 Shah et al. 2008]<br>[http://www.sciencedirect.com/science/article/pii/S0960894X12012747 Forsyth et al. 2012] |
| − | stilbenoid | + | |- |
| − | (diaryleten) | + | |36 |
| − | 0.060 | + | !scope="row" style="background-color:LemonChiffon" |CEP33779<br>(JAK1, JAK3) |
| − | Ba/F3:EpoR, | + | |triazolopyridine |
| − | HEL | + | |0.0018 |
| − | - | + | |irf1-bla TF-1 (IC<sub>50</sub>) |
| − | + | |0.061 | |
| − | 4.0 | + | |[http://dx.doi.org/10.1021/jm300248q Dugan et al. 2012] |
| − | Kiss et al. 2009 | + | |- |
| − | Majumder et al. 2010 | + | |37 |
| − | Kirabo et al. 2011 | + | !scope="row" style="background-color:LemonChiffon" |"29"<br>(JAK1, JAK3, TYK2) |
| − | + | |triazolopyridine | |
| − | NVP-BSK805 | + | |0.0017 |
| − | (JAK1,TYK2,ABL) | + | |SET-2 (IC<sub>50</sub>) |
| − | diarylquinoxaline | + | |0.212 |
| − | 0.00048 | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X13007178 Siu et al. 2013] |
| − | 0.00058 | + | |- |
| − | 0.00056 | + | |38 |
| − | Ba/F3: | + | !scope="row" style="background-color:LemonChiffon" |"6"<br>(JAK1, JAK3, TYK2) |
| − | SET-2 | + | |imidazopyrrolopyridine |
| − | MB-02 | + | |0.0021 |
| − | UKE-1 | + | |TF-1-EPO (IC<sub>50</sub>) |
| − | MUTZ-8 | + | |0.097 |
| − | 0.039 | + | |[http://dx.doi.org/10.1021/jm300628c Zak et al. 2012] |
| − | 0.051 | + | |- |
| − | 0.064 | + | |39 |
| − | 0.071 | + | !scope="row" style="background-color:LemonChiffon" |"7"<br>(JAK1, JAK3, TYK2) |
| − | 0.331 | + | |imidazopyrrolopyridine |
| − | Baffert et al. 2010 | + | |0.0012 |
| − | + | |TF-1-EPO (IC<sub>50</sub>) | |
| − | 26 | + | |0.86 |
| − | (ABL) | + | |[http://dx.doi.org/10.1021/jm300438j Kulagowski et al. 2012] |
| − | diarylquinoxaline | + | |- |
| − | 0.0073 | + | |40 |
| − | SET-2 | + | !scope="row" style="background-color:LemonChiffon" |"31"<br>(JAK1, JAK3, TYK2) |
| − | 0.088 | + | |imidazopyrrolopyridine |
| − | Pissot-Soldermann et al. 2010 | + | |0.068 |
| − | + | |TF-1-EPO (IC<sub>50</sub>) | |
| − | hexabromo cyclohexane | + | |7.68 |
| − | + | |[http://dx.doi.org/10.1021/jm4004895 Zak et al. 2013] | |
| − | low | + | |- |
| − | + | |41 | |
| − | - | + | !scope="row" style="background-color:LemonChiffon" |"46"<br>(JAK1, TYK2) |
| − | Sandberg et al. 2005 | + | |pyridine amide |
| − | + | |0.028 | |
| − | XL019 | + | |TF-1-EPO (IC<sub>50</sub>) |
| − | (JAK1,JAK3,FLT3, | + | |1.7 |
| − | PDGFRB,cKIT) | + | |[http://www.sciencedirect.com/science/article/pii/S0223523413002304 Liang et al. 2013] |
| − | arylaminopyrimidine | + | |- |
| − | 0.002 | + | |42 |
| − | HEL | + | !scope="row" style="background-color:LemonChiffon" |"7j"<br>(JAK1, JAK3, TYK2) |
| − | - | + | |pyrazolopyrimidine |
| − | Paquette et al. 2008 | + | |0.0001 |
| − | Shah et al. 2008 | + | |SET-2 (IC<sub>50</sub>)<br>TF-1-EPO (IC<sub>50</sub>) |
| − | Forsyth et al. 2012 | + | |0.0039<br>0.0074 |
| − | + | |[http://dx.doi.org/10.1021/jm3012239 Hanan et al. 2012] | |
| − | CEP33779 | + | |- |
| − | (JAK1,JAK3) | + | |43 |
| − | triazolopyridine | + | !scope="row" style="background-color:LemonChiffon" |"6"<br>(JAK3) |
| − | 0.0018 | + | |pyrazolopyrimidine amine |
| − | irf1-bla TF-1 ( | + | |0.003 |
| − | 0.061 | + | |Ba/F3:TEL-JAK2<br>SET-2<br>UKE1 |
| − | Dugan et al. 2012 | + | |0.006<br>0.078<br>0.050 |
| − | + | |[http://www.sciencedirect.com/science/article/pii/S0960894X13002989 Guan et al. 2013] | |
| − | 29 | + | |- |
| − | (JAK1,JAK3,TYK2) | + | |44 |
| − | triazolopyridine | + | !scope="row" style="background-color:LemonChiffon" |"19a"<br>(JAK1, JAK3, CK2α2, KDR, ABL, FGR, TRKA, FLT4, FLT3, RET, ALK, FGFR1, AuroraA, LIMK1) |
| − | 0.0017 | + | |methylimidazole |
| − | SET-2 ( | + | |0.002 |
| − | 0.212 | + | |Ba/F3:TEL-JAK2<br>SET-2<br>UKE1 |
| − | Siu et al. 2013 | + | |0.012<br>0.014<br>0.055 |
| − | + | |[http://dx.doi.org/10.1021/jm401546n Su et al. 2014] | |
| − | 6 | + | |- |
| − | (JAK1,JAK3,TYK2) | + | |45 |
| − | imidazopyrrolopyridine | + | !scope="row" style="background-color:LemonChiffon" |NS-018<br>(JAK1, JAK3, TYK2, SRC, FYN, YES, LYNa, FGR, LCK, HCK, ABL, FLT3) |
| − | 0.0021 | + | |pyrazinopyridine diamine |
| − | TF-1-EPO ( | + | |0.00072 |
| − | 0.097 | + | |Ba/F3:JAK2<sup>V617F</sup><br>Ba/F3:TEL-JAK2<br>Ba/F3:MPL<sup>W515L</sup><br>SET-2<br>Ba/F3:TEL-JAK3<br>MV4-11(FLT3-ITD) |
| − | Zak et al. 2012 | + | |0.060 0.011 0.061 0.120 0.800 0.730 |
| − | + | |[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255248/ Nakaya et al. 2011]<br>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913942/ Nakaya et al. 2014] | |
| − | 7 | ||
| − | (JAK1,JAK3,TYK2) | ||
| − | imidazopyrrolopyridine | ||
| − | 0.0012 | ||
| − | TF-1-EPO ( | ||
| − | 0.86 | ||
| − | Kulagowski et al. 2012 | ||
| − | |||
| − | 31 | ||
| − | (JAK1,JAK3,TYK2) | ||
| − | imidazopyrrolopyridine | ||
| − | 0.068 | ||
| − | TF-1-EPO ( | ||
| − | 7.68 | ||
| − | Zak et al. 2013 | ||
| − | |||
| − | 46 | ||
| − | (JAK1,TYK2) | ||
| − | pyridine amide | ||
| − | 0.028 | ||
| − | TF-1-EPO ( | ||
| − | 1.7 | ||
| − | Liang et al. 2013 | ||
| − | |||
| − | 7j | ||
| − | (JAK1,JAK3,TYK2) | ||
| − | pyrazolopyrimidine | ||
| − | 0.0001 | ||
| − | SET-2 ( | ||
| − | TF-1-EPO ( | ||
| − | 0.0039 | ||
| − | 0.0074 | ||
| − | Hanan et al. 2012 | ||
| − | |||
| − | 6 | ||
| − | (JAK3) | ||
| − | pyrazolopyrimidine amine | ||
| − | 0.003 | ||
| − | Ba/F3:TEL-JAK2 | ||
| − | SET-2 | ||
| − | UKE1 | ||
| − | 0.006 | ||
| − | 0.078 | ||
| − | 0.050 | ||
| − | Guan et al. 2013 | ||
| − | |||
| − | 19a | ||
| − | (JAK1,JAK3, | ||
| − | KDR,ABL,FGR,TRKA,FLT4,FLT3,RET,ALK, | ||
| − | FGFR1,AuroraA, | ||
| − | LIMK1) | ||
| − | methylimidazole | ||
| − | 0.002 | ||
| − | Ba/F3:TEL-JAK2 | ||
| − | SET-2 | ||
| − | UKE1 | ||
| − | 0.012 | ||
| − | 0.014 | ||
| − | 0.055 | ||
| − | Su et al. 2014 | ||
|} | |} | ||
Aktualna wersja na dzień 16:07, 28 lis 2015
Small molecule inhibitors of the tyrosine kinase JAK2
| Nb | inhibitor (other kinase targets) |
chemical class | enzymatic test | cell test | references | |
|---|---|---|---|---|---|---|
| IC50 (µM) | cell line | GI50 (µM) | ||||
| 1 | AG490 (EGFR, PDGFR) |
tyrphostin | 36.4 48 145.3 |
B-precursor (KOCL-33,-45, -50,-69,KOPN-30bi,-55bi, -57bi,-72bi,KOPN-32,-62, -84,NALM 6) T-precursor (KOPT-K1,-5, -11,Jurkat) Ba/F3:JAK2V617F HEL (JAK2V617F) SET-2 (JAK2V617F/wt) XG-1 XG-2 U266 MDAH2774 Caov-3 MDA-MB-468 |
- - 1.0 >20.0 >20.0 14.8 12.9 26.0 - - - |
Gazit et al. 1989 Gazit et al. 1991 Meydan et al. 1996 Vos et al. 2000 Miyamoto et al. 2001 Burke et al. 2001 Duhé et al. 2002 Reddy et al. 2010 Jatiani et al. 2010 |
| 2 | LS104 (BCR-ABL) |
tyrphostin | 2.52 0.1-0.6 |
Ba/F3:EpoR,JAK2V617F Ba/F3:EpoR,JAK2wt HEL |
1.5 10.0 |
Grunberger et al. 2003 Lipka et al. 2008 |
| 3 | WP1066 | tyrphostin | - | HEL | 2.3 | Verstovsek et al. 2008 |
| 4 | ON044580 (BCR-ABL) |
α-benzoyl styryl benzyl sulfide | 0.9-1.2 4.2 |
Ba/F3:JAK2V617F HEL SET-2 |
0.25 0.90 3.00 |
Reddy et al. 2010 Jatiani et al. 2010 Samanta et al. 2010 |
| 5 | lestaurtinib (CEP701) (FLT3,JAK3) |
indolocarbazole | 0.001 | HEL | 0.03-0.10 | Hexner et al. 2008 Santos et al. 2010 |
| 6 | Gö6976 (JAK3, FLT3, PKCα,β1) |
indolocarbazole | 0.13 | 32D 32D:TEL-JAK2 FDCP1 TF-1 Mo7E HEL |
0.093 0.242 - - - - |
Grandage et al. 2006 |
| 7 | TG02 (CDKs, TYK2, FLT3, TYRO3, ERK5, p38δ, Fms, Lck, Fyn, JAK1) |
pyrimidine | - | HEL SET-2 Ba/F3:JAK2wt Ba/F3:JAK2V617F Karpas-1106P 32D |
0.202 0.231 0.156 0.099 0.068 0.098 |
Goh et al. 2012 Pallis et al. 2012 |
| 8 | TG101209 (FLT3, RET, JAK3) |
pyrimidine | 0.006 | Ba/F3:JAK2V617F HEL multiple myeloma cell lines (RPMI8226, MM1S, OPM2, NCI-H929, Dox40, MM1R, LR5) |
0.2 2-5 - |
Pardanani et al. 2007 Wang and Fiskus et al. 2009 Ramakrishnan et al. 2010 |
| 9 | TG101348 (FLT3, RET, JAK1, JAK3, TYK2) |
pyrimidine | 0.003 | Ba/F3:JAK2V617F HEL |
0.270 0.305 |
Wernig et al. 2008 Pardanani et al. 2009 Pardanani et al. 2011 |
| 10 | R723 (JAK3, TYK2, FLT3, PRKD2, TBK1, SYK, PAK4, DAPK3, PRKD1, MYLK2, PRKCN, STK22D, IKBKE) |
pyrimidine | 0.002 | Ba/F3:JAK2V617F | 0.13-0.20 | Shide et al. 2009 Shide et al. 2011 |
| 11 | INCB018424 (JAK1, JAK3, TYK2) |
pyrrolopyrimidine | 0.0045 | - | - | Fridman et al. 2007 Verstovsek et al. 2007 Verstovsek et al. 2008 Verstovsek et al. 2010 Quintás-Cardama et al. 2010 Mesa et al. 2011 |
| 12 | INCB16562 (JAK1, JAK3) |
pyrrolopyrimidine | 0.0003 | Ba/F3:JAK2V617F Ba/F3:JAK2K539L Ba/F3:MPLW515L Ba/F3:TEL-JAK2 SET-2 UKE-1 |
0.177 0.406 0.600 0.168 0.046 0.573 |
Koppikar et al. 2010 |
| 13 | CP690550 (JAK1, JAK3, TYK2) |
pyrrolopyrimidine | 0.0041 0.011 0.012 0.020 |
FDCP-EpoR,JAK2wt FDCP-EpoR,JAK2V617F |
2.1 0.25 |
Changelian et al. 2003 Chen et al. 2006 Clark et al. 2007 Manshouri et al. 2008 Meyer et al. 2010 Thoma et al. 2011 |
| 14 | AZD1480 (JAK1, JAK3, TRKA, AuroraA, FLT4, FGFR1, ARK5) |
pyrazolopyrimidine | 0.003 | Ba/F3:TEL-JAK2 SET-2 UKE1 HEL |
0.06 0.016 0.054 0.39 |
Hedvat et al. 2009 Ioannidis et al. 2011 |
| 15 | CYT387 (JAK1, TYK2, CDK2/cyclinA, JNK1, PRKCN, PRKD1, ROCK2, TBK1) |
aminopyrimidine | 0.018 | Ba/F3:EpoR,JAK2V617F 32D:EpoR,JAK2V617F HEL TF-1 U266 CHRF-288-11:JAK2T875N Ba/F3:TEL-JAK2 |
0.5 1.5 1.5 1.25 0.75 0.001 0.724 |
Pardanani et al. 2009 Tyner et al. 2010 |
| 16 | SGI1252 (JAK1, JAK3, TYK2, YES, FLT3, ABL, SRC, LCK) |
diaminopyrimidine | 0.0054 0.002 0.0197 |
FDCP-EpoR,JAK2wt FDCP-EpoR,JAK2V617F HEL SET-2 UKE-1 |
0.074 0.110 0.441 0.055 0.089 |
Olsen et al. 2008 Riaz Ahmed et al. 2008 Riaz Ahmed et al. 2011 |
| 17 | SB1518 (FLT3, JAK1, JAK3, TYK2) |
aminopyrimidine macrocycle | 0.023 0.019 |
Ba/F3:JAK2V617F HEL SET-2 Karpas-1106P U266 |
0.16 1.726 0.217 0.348 1.350 |
Hart et al. 2011 William et al. 2011 |
| 18 | "38" (JAK1, TYK2, JAK3, MEKK2, MEKK3) |
8-oxo-pyridopyrimidine | 0.001 | TF-1-EPO (IC50) | 0.115 | Labadie et al. 2013 |
| 19 | Z3 | pyridine | 15.0 28.0 |
HEL | - | Sayyah et al. 2008 |
| 20 | "25" (JAK1, GAK, YSK4) |
thienopyridine | 0.002 | Ba/F3:TEL-JAK2 (IC50) | 1.62 | Schenkel et al. 2011 |
| 21 | "65" (JAK1, cSRC, TRKA, ACK1, FMS, FYN, FLT3, HCK, RET, BMX, LYN, FGR, LCK, ARK5, BTK, YES, PTK5, TRKB, CaMKIIδ,γ, PRK2, ARG, MLK1, ALK) |
pyridoindolcarboxamide | 0.0008 | irf1-bla HEL (IC50) | 0.025 | Lim et al. 2011 |
| 22 | AT9283 (AuroraK, JAK3, FLT3, ABL) |
pyrazole benzimidazole | 0.0012 | HEL (JAK2V617F) SET-2 (JAK2V617F/wt) Ba/F3:ETV6-JAK2 Ba/F3-IL-3 TF-1-IL-3 CMK (JAK2A572V) |
0.110 0.057 0.016 0.017 0.040 0.026 |
Howard et al. 2009 Dawson et al. 2010 |
| 23 | AZ960 (TRKA, AuroraA, ARK5, ALK, CaMKII, FLT4, FGFR1, LIMK1, BrSK2, FAK) |
pyrazole nicotinonitrile | 0.003 | SET-2 (JAK2V617F/wt) Ba/F3:TEL-JAK2 HTLV-1 infected T cells (MT-1, MT-2) |
0.033 0.025 - |
Gozgit et al. 2008 Yang et al. 2010 |
| 24 | CMP6 (JAK1, JAK3, TYK2) |
pyridone tetracycle | 0.001 | CTLL-2 B9 U266 KMS11 |
0.052-0.1 0.25 - - |
Thompson et al. 2002 Lucet et al. 2006 Pedranzini et al. 2006 |
| 25 | "13" | sulfonamide aminoindazole | 0.078 | - | - | Antonysamy et al. 2009 |
| 26 | comp 9 (JAK3, ALK, cKIT, GCK) |
polycyclic azaindole | 0.001 | TF-1-GMCSF (IC50) HT2-IL2 (IC50) |
0.27 1.53 |
Wang et al. 2009 |
| 27 | "15a" | polycyclic azaindole | 0.0008 | TF-1-GMCSF (IC50) | 0.16 | Wang et al. 2010 |
| 28 | "40" (JAK3) |
aminopyrazolopyrimidine | 0.0002 | TF-1-GMCSF (IC50) HT2-IL2 (IC50) |
0.16 3.2 |
Ledeboer et al. 2009 |
| 29 | "29" (JAK1, JAK3) |
pyrrolotriazine aminopyrrazole | 0.0018 | SET-2 | 0.11 | Harikrishnan et al. 2011 |
| 30 | atiprimod (JAK3) |
azaspirane | - | FDCP-EpoR,JAK2wt FDCP-EpoR,JAK2V617F SET-2 |
0.69 0.42 0.53 |
Hamasaki et al. 2005 Quintás-Cardama et al. 2011 |
| 31 | G6 | stilbenoid (diaryleten) |
0.060 | Ba/F3:EpoR,JAK2V617F HEL |
- 4.0 |
Kiss et al. 2009 Majumder et al. 2010 Kirabo et al. 2011 |
| 32 | NVP-BSK805 (JAK1, TYK2, ABL) |
diarylquinoxaline | 0.00048 0.00058 0.00056 |
Ba/F3:JAK2V617F SET-2 MB-02 UKE-1 MUTZ-8 |
0.039 0.051 0.064 0.071 0.331 |
Baffert et al. 2010 |
| 33 | "26" (ABL) |
diarylquinoxaline | 0.0073 | SET-2 | 0.088 | Pissot-Soldermann et al. 2010 |
| 34 | hexabromo cyclohexane | cyclohexane | low µM | γ-2A | - | Sandberg et al. 2005 |
| 35 | XL019 (JAK1, JAK3, FLT3, PDGFRB, cKIT) |
arylaminopyrimidine | 0.002 | HEL | - | Paquette et al. 2008 Shah et al. 2008 Forsyth et al. 2012 |
| 36 | CEP33779 (JAK1, JAK3) |
triazolopyridine | 0.0018 | irf1-bla TF-1 (IC50) | 0.061 | Dugan et al. 2012 |
| 37 | "29" (JAK1, JAK3, TYK2) |
triazolopyridine | 0.0017 | SET-2 (IC50) | 0.212 | Siu et al. 2013 |
| 38 | "6" (JAK1, JAK3, TYK2) |
imidazopyrrolopyridine | 0.0021 | TF-1-EPO (IC50) | 0.097 | Zak et al. 2012 |
| 39 | "7" (JAK1, JAK3, TYK2) |
imidazopyrrolopyridine | 0.0012 | TF-1-EPO (IC50) | 0.86 | Kulagowski et al. 2012 |
| 40 | "31" (JAK1, JAK3, TYK2) |
imidazopyrrolopyridine | 0.068 | TF-1-EPO (IC50) | 7.68 | Zak et al. 2013 |
| 41 | "46" (JAK1, TYK2) |
pyridine amide | 0.028 | TF-1-EPO (IC50) | 1.7 | Liang et al. 2013 |
| 42 | "7j" (JAK1, JAK3, TYK2) |
pyrazolopyrimidine | 0.0001 | SET-2 (IC50) TF-1-EPO (IC50) |
0.0039 0.0074 |
Hanan et al. 2012 |
| 43 | "6" (JAK3) |
pyrazolopyrimidine amine | 0.003 | Ba/F3:TEL-JAK2 SET-2 UKE1 |
0.006 0.078 0.050 |
Guan et al. 2013 |
| 44 | "19a" (JAK1, JAK3, CK2α2, KDR, ABL, FGR, TRKA, FLT4, FLT3, RET, ALK, FGFR1, AuroraA, LIMK1) |
methylimidazole | 0.002 | Ba/F3:TEL-JAK2 SET-2 UKE1 |
0.012 0.014 0.055 |
Su et al. 2014 |
| 45 | NS-018 (JAK1, JAK3, TYK2, SRC, FYN, YES, LYNa, FGR, LCK, HCK, ABL, FLT3) |
pyrazinopyridine diamine | 0.00072 | Ba/F3:JAK2V617F Ba/F3:TEL-JAK2 Ba/F3:MPLW515L SET-2 Ba/F3:TEL-JAK3 MV4-11(FLT3-ITD) |
0.060 0.011 0.061 0.120 0.800 0.730 | Nakaya et al. 2011 Nakaya et al. 2014 |