Z BioInf
(→Niskocząsteczkowe inhibitory domeny kinazowej JAK2) |
(→Niskocząsteczkowe inhibitory domeny kinazowej JAK2) |
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| Linia 20: | Linia 20: | ||
|<br>-<br>-<br>1.0<br>>20.0<br>>20.0<br>14.8<br>12.9<br>26.0<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. 1989,1991<br>Meydan et al. 1996<br>Vos et al. 2000<br>Miyamoto et al. 2001<br>Burke et al. 2001<br>Duhé et al. 2002<br>Reddy et al. 2010<br>Jatiani et al. 2010 | |Gazit et al. 1989,1991<br>Meydan et al. 1996<br>Vos et al. 2000<br>Miyamoto et al. 2001<br>Burke et al. 2001<br>Duhé et al. 2002<br>Reddy et al. 2010<br>Jatiani et al. 2010 | ||
| − | | | + | |- |
|2 | |2 | ||
| − | |LS104 | + | |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>Ba/F3:EpoR,JAK2<sup>wt</sup><br>HEL |
| − | |Ba/F3:EpoR, | + | |1.5<br>10.0 |
| − | Ba/F3:EpoR, | + | |Grunberger et al. 2003<br>Lipka et al. 2008 |
| − | HEL | + | |- |
| − | |1.5 | ||
| − | 10.0 | ||
| − | |Grunberger et al. 2003 | ||
| − | Lipka et al. 2008 | ||
| − | | | ||
|3 | |3 | ||
|WP1066 | |WP1066 | ||
|tyrphostin | |tyrphostin | ||
| − | |- | + | |<nowiki>-</nowiki> |
| − | HEL | + | |HEL |
|2.3 | |2.3 | ||
|Verstovsek et al. 2008 | |Verstovsek et al. 2008 | ||
| − | | | + | |- |
|4 | |4 | ||
| − | |ON044580 | + | |ON044580<br>(BCR-ABL) |
| − | (BCR-ABL) | ||
|&alfa;-benzoyl styryl benzyl sulfide | |&alfa;-benzoyl styryl benzyl sulfide | ||
| − | |0.9-1.2 | + | |0.9-1.2<br>4.2 |
| − | 4.2 | + | |Ba/F3:JAK2<sup>V617F</sup><br>HEL<br>SET-2 |
| − | |Ba/F3: | + | |0.25<br>0.90<br>3.00 |
| − | HEL | + | |Reddy et al. 2010<br>Jatiani et al. 2010<br>Samanta et al. 2010 |
| − | SET-2 | + | |- |
| − | |0.25 | ||
| − | 0.90 | ||
| − | 3.00 | ||
| − | |Reddy et al. 2010 | ||
| − | Jatiani et al. 2010 | ||
| − | Samanta et al. 2010 | ||
| − | | | ||
|5 | |5 | ||
| − | |CEP701 | + | |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 | + | |Hexner et al. 2008<br>Santos et al. 2010 |
| − | Santos et al. 2010 | + | |- |
| − | | | ||
|6 | |6 | ||
| − | |Go6976 | + | |Go6976<br>(JAK3, FLT3, PKC&alfa;,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 | ||
| − | TF-1 | ||
| − | Mo7E | ||
| − | HEL | ||
| − | |0.093 | ||
| − | 0.242 | ||
| − | - | ||
| − | - | ||
| − | - | ||
| − | - | ||
|Grandage et al. 2006 | |Grandage et al. 2006 | ||
| − | | | + | |- |
|7 | |7 | ||
| − | |TG02 | + | |TG02<br>(CDKs, FLT3) |
| − | (CDKs, | ||
| − | FLT3) | ||
|pyrimidine | |pyrimidine | ||
| − | |-HEL | + | |- |
| − | 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: | ||
| − | Karpas-1106P | ||
| − | 32D | ||
| − | |0.202 | ||
| − | 0.231 | ||
| − | 0.156 | ||
| − | 0.099 | ||
| − | 0.068 | ||
| − | 0.098 | ||
|Goh et al. 2011 | |Goh et al. 2011 | ||
| − | | | + | |- |
|8 | |8 | ||
| − | |TG101209 | + | |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>- |
| − | + | |Pardanani et al. 2007<br>Wang and Fiskus et al. 2009<br>Ramkrishnan et al. 2010 | |
| − | |0.2 | ||
| − | 2-5 | ||
|- | |- | ||
| − | |||
| − | |||
| − | |||
| − | |||
|9 | |9 | ||
| − | |TG101348 | + | |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 | + | |Wernig et al. 2008<br>Animesh et al. 2009<br>Pardanani et al. 2011 |
| − | 0.305 | + | |- |
| − | |Wernig et al. 2008 | ||
| − | Animesh et al. 2009 | ||
| − | Pardanani et al. 2011 | ||
| − | | | ||
|10 | |10 | ||
| − | |R723 | + | |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 | + | |Shide et al. 2009<br>Shide et al. 2011 |
| − | Shide et al. 2011 | + | |- |
| − | | | ||
|11 | |11 | ||
| − | |INCB018424 | + | |INCB018424<br>(JAK1, JAK3, TYK2) |
| − | (JAK1,JAK3,TYK2) | ||
|pyrrolopyrimidine | |pyrrolopyrimidine | ||
|0.0045 | |0.0045 | ||
| − | - | + | |<nowiki>-</nowiki> |
| − | - | + | |<nowiki>-</nowiki> |
| − | |Verstovsek et al. 2008 | + | |Verstovsek et al. 2008<br>Verstovsek et al. 2010<br>Mesa 2010 |
| − | Mesa 2010 | + | |- |
| − | | | ||
|12 | |12 | ||
| − | |INCB16562 | + | |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: | ||
| − | Ba/F3:TEL-JAK2 | ||
| − | SET-2 | ||
| − | UKE-1 | ||
| − | |0.177 | ||
| − | 0.406 | ||
| − | 0.600 | ||
| − | 0.168 | ||
| − | 0.046 | ||
| − | 0.573 | ||
|Koppikar et al. 2010 | |Koppikar et al. 2010 | ||
| − | | | + | |- |
|13 | |13 | ||
| − | |CP690550 | + | |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 | + | |Changelian et al. 2003<br>Chen et al. 2006<br>Clark et al. 2007<br>Manshouri et al. 2008<br>Meyer et al. 2010<br>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 | + | |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 | + | |Hedvat et al. 2009<br>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 | + | |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 | + | |Pardanani et al. 2009<br>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 | + | |SGI1252<br>(JAK1, JAK3, TYK2, YES, FLT3, ABL, SRC, LCK) |
| − | (JAK1,JAK3,TYK2, | ||
| − | YES,FLT3,ABL,SRC, | ||
| − | LCK) | ||
|diaminopyrimidine | |diaminopyrimidine | ||
| − | |0.002 | + | |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, | + | |Olsen et al. 2008<br>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 | + | |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 | + | |Hart et al. 2011<br>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 | |Z3 | ||
|pyridine | |pyridine | ||
| − | |15.0 | + | |15.0<br>28.0 |
| − | 28.0 | ||
|HEL | |HEL | ||
|Sayyah et al. 2008 | |Sayyah et al. 2008 | ||
| − | | | + | |- |
|19 | |19 | ||
| − | |25(JAK1,GAK,YSK4) | + | |"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 | |Schenkel et al. 2011 | ||
| − | | | + | |- |
|20 | |20 | ||
| − | |65 | + | |"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 | + | |Lim et al. 2011 |
| − | 21 | + | |- |
| − | AT9283 | + | |21 |
| − | (AuroraK,JAK3, FLT3,ABL) | + | |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 | + | |Howard et al. 2009<br>Dawson et al. 2010 |
| − | Ba/F3-IL-3 | + | |- |
| − | TF-1-IL-3 | + | |22 |
| − | CMK ( | + | |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 | + | |Gozgit et al. 2008<br>Yang et al. 2010 |
| − | 0.026 | + | |- |
| − | Howard et al. 2009 | + | |23 |
| − | Dawson et al. 2010 | + | |CMP6<br>(JAK1, JAK3, TYK2) |
| − | 22 | + | |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, | + | |Thompson et al. 2002<br>Lucet et al. 2006<br>Pedranzini et al. 2008 |
| − | BrSK2,FAK) | + | |- |
| − | pyrazole nicotinonitrile | + | |24 |
| − | 0.003 | + | |"13" |
| − | SET-2 ( | + | |sulfonamide aminoindazole |
| − | Ba/F3:TEL-JAK2 | + | |0.078<br>-<br>- |
| − | HTLV-1 infected T cells (MT-1, MT-2) | + | |Antonysamy et al. 2009 |
| − | 0.033 | + | |- |
| − | 0.025 | + | |25 |
| − | - | + | |comp 9<br>(JAK3, ALK, cKIT, GCK) |
| − | + | |polycyclic azaindole | |
| − | Gozgit et al. 2008 | + | |0.001 |
| − | Yang et al. 2010 | + | |TF-1-GMCSF (IC<sub>50</sub>)<br>HT2-IL2 (IC<sub>50</sub>) |
| − | 23 | + | |0.27<br>1.53 |
| − | CMP6 | + | |Wang et al. 2009 |
| − | (JAK1, | + | |- |
| − | JAK3, | + | |26 |
| − | TYK2) | + | |"15a" |
| − | pyridone tetracycle | + | |polycyclic azaindole |
| − | 0.001 | + | |0.0008 |
| − | CTLL-2 | + | |TF-1-GMCSF (IC<sub>50</sub>) |
| − | B9 | + | |0.16 |
| − | U266 | + | |Wang et al. 2010 |
| − | KMS11 | + | |- |
| − | 0.052-0.1 | + | |27 |
| − | 0.25 | + | |"40"<br>(JAK3) |
| − | - | + | |aminopyrazolopyrimidine |
| − | - | + | |0.0002 |
| − | Thompson et al. 2002 | + | |TF-1-GMCSF (IC<sub>50</sub>)<br>HT2-IL2 (IC<sub>50</sub>) |
| − | Lucet et al. 2006 | + | |0.16<br>3.2 |
| − | Pedranzini et al. 2008 | + | |Ledeboer et al. 2009 |
| − | 24 | + | |- |
| − | 13 | + | |28 |
| − | sulfonamide aminoindazole | + | |"29"<br>(JAK1, JAK3) |
| − | 0.078 | + | |pyrrolotriazine aminopyrrazole |
| − | - | + | |0.0018 |
| − | - | + | |SET-2 |
| − | Antonysamy et al. 2009 | + | |0.11 |
| − | 25 | + | |Harikrishnan et al. 2011 |
| − | comp 9 | + | |- |
| − | (JAK3,ALK, | + | |29 |
| − | cKIT,GCK) | + | |atiprimod<br>(JAK3) |
| − | polycyclic azaindole | + | |azaspirane |
| − | 0.001 | + | |<nowiki>-</nowiki> |
| − | TF-1-GMCSF ( | + | |FDCP-EpoR,JAK2<sup>wt</sup><br>FDCP-EpoR,JAK2<sup>V617F</sup><br>SET-2 |
| − | HT2-IL2 ( | + | |0.69<br>0.42<br>0.53 |
| − | 0.27 | + | |Hamasaki et al. 2005<br>Quintás-Cardama et al. 2011 |
| − | 1.53 | + | |- |
| − | Wang et al. 2009 | + | |30 |
| − | 26 | + | |G6 |
| − | 15a | + | |stilbenoid<br>(diaryleten) |
| − | polycyclic azaindole | + | |0.060 |
| − | 0.0008 | + | |Ba/F3:EpoR,JAK2<sup>V617F</sup><br>HEL |
| − | TF-1-GMCSF ( | + | |<nowiki>-</nowiki><br>4.0 |
| − | 0.16 | + | |Kiss et al. 2009<br>Majumder et al. 2010<br>Kirabo et al. 2011 |
| − | Wang et al. 2010 | + | |- |
| − | 27 | + | |31 |
| − | 40 | + | |NVP-BSK805<br>(JAK1, TYK2, ABL) |
| − | (JAK3) | + | |diarylquinoxaline |
| − | aminopyrazolopyrimidine | + | |0.00048<br>0.00058<br>0.00056 |
| − | 0.0002 | + | |Ba/F3:JAK2<sup>V617F</sup><br>SET-2<br>MB-02<br>UKE-1<br>MUTZ-8 |
| − | TF-1-GMCSF ( | + | |0.039<br>0.051<br>0.064<br>0.071<br>0.331 |
| − | HT2-IL2 ( | + | |Baffert et al. 2010 |
| − | 0.16 | + | |- |
| − | 3.2 | + | |32 |
| − | Ledeboer et al. 2009 | + | |"26"<br>(ABL) |
| − | 28 | + | |diarylquinoxaline |
| − | 29 | + | |0.0073 |
| − | (JAK1,JAK3) | + | |SET-2 |
| − | pyrrolotriazine aminopyrrazole | + | |0.088 |
| − | 0.0018 | + | |Pissot-Soldermann et al. 2010 |
| − | SET-2 | + | |- |
| − | 0.11 | + | |33 |
| − | Harikrishnan et al. 2011 | + | |hexabromo cyclohexane |
| − | 29 | + | |cyclohexane |
| − | atiprimod | + | |low µM |
| − | (JAK3) | + | |g-2A |
| − | azaspirane | + | |<nowiki>-</nowiki> |
| − | - | + | |Sandberg et al. 2005 |
| − | FDCP-EpoR, | + | |- |
| − | FDCP-EpoR, | + | |34 |
| − | SET-2 | + | |XL019<br>(JAK1, JAK3, FLT3, PDGFRB, cKIT) |
| − | 0.69 | + | |arylaminopyrimidine |
| − | 0.42 | + | |0.002 |
| − | 0.53 | + | |HEL |
| − | Hamasaki et al. 2005 | + | |<nowiki>-</nowiki> |
| − | Quintás-Cardama et al. 2011 | + | |Paquette et al. 2008<br>Shah et al. 2008<br>Forsyth et al. 2012 |
| − | 30 | + | |- |
| − | G6 | + | |35 |
| − | stilbenoid | + | |CEP33779<br>(JAK1, JAK3) |
| − | (diaryleten) | + | |triazolopyridine |
| − | 0.060 | + | |0.0018 |
| − | Ba/F3:EpoR, | + | |irf1-bla TF-1 (IC<sub>50</sub>) |
| − | HEL | + | |0.061 |
| − | - | + | |Dugan et al. 2012 |
| − | + | |- | |
| − | 4.0 | + | |36 |
| − | Kiss et al. 2009 | + | |"29"<br>(JAK1, JAK3, TYK2) |
| − | Majumder et al. 2010 | + | |triazolopyridine |
| − | Kirabo et al. 2011 | + | |0.0017 |
| − | 31 | + | |SET-2 (IC<sub>50</sub>) |
| − | NVP-BSK805 | + | |0.212 |
| − | (JAK1,TYK2,ABL) | + | |Siu et al. 2013 |
| − | diarylquinoxaline | + | |- |
| − | 0.00048 | + | |37 |
| − | 0.00058 | + | |"6"<br>(JAK1, JAK3, TYK2) |
| − | 0.00056 | + | |imidazopyrrolopyridine |
| − | Ba/F3: | + | |0.0021 |
| − | SET-2 | + | |TF-1-EPO (IC<sub>50</sub>) |
| − | MB-02 | + | |0.097 |
| − | UKE-1 | + | |Zak et al. 2012 |
| − | MUTZ-8 | + | |- |
| − | 0.039 | + | |38 |
| − | 0.051 | + | |"7"<br>(JAK1, JAK3, TYK2) |
| − | 0.064 | + | |imidazopyrrolopyridine |
| − | 0.071 | + | |0.0012 |
| − | 0.331 | + | |TF-1-EPO (IC<sub>50</sub>) |
| − | Baffert et al. 2010 | + | |0.86 |
| − | 32 | + | |Kulagowski et al. 2012 |
| − | 26 | + | |- |
| − | (ABL) | + | |39 |
| − | diarylquinoxaline | + | |"31"<br>(JAK1, JAK3, TYK2) |
| − | 0.0073 | + | |imidazopyrrolopyridine |
| − | SET-2 | + | |0.068 |
| − | 0.088 | + | |TF-1-EPO (IC<sub>50</sub>) |
| − | Pissot-Soldermann et al. 2010 | + | |7.68 |
| − | 33 | + | |Zak et al. 2013 |
| − | hexabromo cyclohexane | + | |- |
| − | + | |40 | |
| − | low | + | |"46"<br>(JAK1, TYK2) |
| − | g-2A | + | |pyridine amide |
| − | - | + | |0.028 |
| − | Sandberg et al. 2005 | + | |TF-1-EPO (IC<sub>50</sub>) |
| − | 34 | + | |1.7 |
| − | XL019 | + | |Liang et al. 2013 |
| − | (JAK1,JAK3,FLT3, | + | |- |
| − | PDGFRB,cKIT) | + | |41 |
| − | arylaminopyrimidine | + | |"7j"<br>(JAK1, JAK3, TYK2) |
| − | 0.002 | + | |pyrazolopyrimidine |
| − | HEL | + | |0.0001 |
| − | - | + | |SET-2 (IC<sub>50</sub>)<br>TF-1-EPO (IC<sub>50</sub>) |
| − | Paquette et al. 2008 | + | |0.0039<br>0.0074 |
| − | Shah et al. 2008 | + | |Hanan et al. 2012 |
| − | Forsyth et al. 2012 | + | |- |
| − | 35 | + | |42 |
| − | CEP33779 | + | |"6"<br>(JAK3) |
| − | (JAK1,JAK3) | + | |pyrazolopyrimidine amine |
| − | triazolopyridine | + | |0.003 |
| − | 0.0018 | + | |Ba/F3:TEL-JAK2<br>SET-2<br>UKE1 |
| − | irf1-bla TF-1 ( | + | |0.006<br>0.078<br>0.050 |
| − | 0.061 | + | |Guan et al. 2013 |
| − | Dugan et al. 2012 | + | |- |
| − | 36 | + | |43 |
| − | 29 | + | |"19a"<br>(JAK1, JAK3, CK2&alfa;2, KDR, ABL, FGR, TRKA, FLT4, FLT3, RET, ALK, FGFR1, AuroraA, LIMK1) |
| − | (JAK1,JAK3,TYK2) | + | |methylimidazole |
| − | triazolopyridine | + | |0.002 |
| − | 0.0017 | + | |Ba/F3:TEL-JAK2<br>SET-2<br>UKE1 |
| − | SET-2 ( | + | |0.012<br>0.014<br>0.055 |
| − | 0.212 | + | |Su et al. 2014 |
| − | Siu et al. 2013 | ||
| − | 37 | ||
| − | 6 | ||
| − | (JAK1,JAK3,TYK2) | ||
| − | imidazopyrrolopyridine | ||
| − | 0.0021 | ||
| − | TF-1-EPO ( | ||
| − | 0.097 | ||
| − | Zak et al. 2012 | ||
| − | 38 | ||
| − | 7 | ||
| − | (JAK1,JAK3,TYK2) | ||
| − | imidazopyrrolopyridine | ||
| − | 0.0012 | ||
| − | TF-1-EPO ( | ||
| − | 0.86 | ||
| − | Kulagowski et al. 2012 | ||
| − | 39 | ||
| − | 31 | ||
| − | (JAK1,JAK3,TYK2) | ||
| − | imidazopyrrolopyridine | ||
| − | 0.068 | ||
| − | TF-1-EPO ( | ||
| − | 7.68 | ||
| − | Zak et al. 2013 | ||
| − | 40 | ||
| − | 46 | ||
| − | (JAK1,TYK2) | ||
| − | pyridine amide | ||
| − | 0.028 | ||
| − | TF-1-EPO ( | ||
| − | 1.7 | ||
| − | Liang et al. 2013 | ||
| − | 41 | ||
| − | 7j | ||
| − | (JAK1,JAK3,TYK2) | ||
| − | pyrazolopyrimidine | ||
| − | 0.0001 | ||
| − | SET-2 ( | ||
| − | TF-1-EPO ( | ||
| − | 0.0039 | ||
| − | 0.0074 | ||
| − | Hanan et al. 2012 | ||
| − | 42 | ||
| − | 6 | ||
| − | (JAK3) | ||
| − | pyrazolopyrimidine amine | ||
| − | 0.003 | ||
| − | Ba/F3:TEL-JAK2 | ||
| − | SET-2 | ||
| − | UKE1 | ||
| − | 0.006 | ||
| − | 0.078 | ||
| − | 0.050 | ||
| − | Guan et al. 2013 | ||
| − | 43 | ||
| − | 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 | ||
|} | |} | ||
Wersja z 10:45, 17 maj 2014
Niskocząsteczkowe inhibitory domeny kinazowej JAK2
| Lp. | inhibitor (inne hamowane kinazy) |
klasa chemiczna | test enzym. | test komórkowy | literatura | |
|---|---|---|---|---|---|---|
| IC50 (µM) | linia komórkowa | 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. 1989,1991 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,JAK2V617FBa/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) |
&alfa;-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 | CEP701 (FLT3,JAK3) |
indolocarbazole | 0.001 | HEL | 0.03-0.10 | Hexner et al. 2008 Santos et al. 2010 |
| 6 | Go6976 (JAK3, FLT3, PKC&alfa;,β1) |
indolocarbazole | 0.13 | 32D 32D:TEL-JAK2 FDCP1 TF-1 Mo7E HEL |
0.093 0.242 - - - - |
Grandage et al. 2006 |
| 7 | TG02 (CDKs, FLT3) |
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. 2011 | ||||
| 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 Ramkrishnan 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 Animesh 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 | - | - | Verstovsek et al. 2008 Verstovsek et al. 2010 Mesa 2010 |
| 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 | 0.002 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. 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 | Z3 | pyridine | 15.0 28.0 |
HEL | Sayyah et al. 2008 | |
| 19 | "25" (JAK1, GAK, YSK4) |
thienopyridine | 0.002 | Ba/F3:TEL-JAK2 (IC50) | 1.62 | Schenkel et al. 2011 |
| 20 | "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 |
| 21 | 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 |
| 22 | 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 |
| 23 | 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. 2008 |
| 24 | "13" | sulfonamide aminoindazole | 0.078 - - |
Antonysamy et al. 2009 | ||
| 25 | 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 |
| 26 | "15a" | polycyclic azaindole | 0.0008 | TF-1-GMCSF (IC50) | 0.16 | Wang et al. 2010 |
| 27 | "40" (JAK3) |
aminopyrazolopyrimidine | 0.0002 | TF-1-GMCSF (IC50) HT2-IL2 (IC50) |
0.16 3.2 |
Ledeboer et al. 2009 |
| 28 | "29" (JAK1, JAK3) |
pyrrolotriazine aminopyrrazole | 0.0018 | SET-2 | 0.11 | Harikrishnan et al. 2011 |
| 29 | 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 |
| 30 | G6 | stilbenoid (diaryleten) |
0.060 | Ba/F3:EpoR,JAK2V617F HEL |
- 4.0 |
Kiss et al. 2009 Majumder et al. 2010 Kirabo et al. 2011 |
| 31 | 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 |
| 32 | "26" (ABL) |
diarylquinoxaline | 0.0073 | SET-2 | 0.088 | Pissot-Soldermann et al. 2010 |
| 33 | hexabromo cyclohexane | cyclohexane | low µM | g-2A | - | Sandberg et al. 2005 |
| 34 | XL019 (JAK1, JAK3, FLT3, PDGFRB, cKIT) |
arylaminopyrimidine | 0.002 | HEL | - | Paquette et al. 2008 Shah et al. 2008 Forsyth et al. 2012 |
| 35 | CEP33779 (JAK1, JAK3) |
triazolopyridine | 0.0018 | irf1-bla TF-1 (IC50) | 0.061 | Dugan et al. 2012 |
| 36 | "29" (JAK1, JAK3, TYK2) |
triazolopyridine | 0.0017 | SET-2 (IC50) | 0.212 | Siu et al. 2013 |
| 37 | "6" (JAK1, JAK3, TYK2) |
imidazopyrrolopyridine | 0.0021 | TF-1-EPO (IC50) | 0.097 | Zak et al. 2012 |
| 38 | "7" (JAK1, JAK3, TYK2) |
imidazopyrrolopyridine | 0.0012 | TF-1-EPO (IC50) | 0.86 | Kulagowski et al. 2012 |
| 39 | "31" (JAK1, JAK3, TYK2) |
imidazopyrrolopyridine | 0.068 | TF-1-EPO (IC50) | 7.68 | Zak et al. 2013 |
| 40 | "46" (JAK1, TYK2) |
pyridine amide | 0.028 | TF-1-EPO (IC50) | 1.7 | Liang et al. 2013 |
| 41 | "7j" (JAK1, JAK3, TYK2) |
pyrazolopyrimidine | 0.0001 | SET-2 (IC50) TF-1-EPO (IC50) |
0.0039 0.0074 |
Hanan et al. 2012 |
| 42 | "6" (JAK3) |
pyrazolopyrimidine amine | 0.003 | Ba/F3:TEL-JAK2 SET-2 UKE1 |
0.006 0.078 0.050 |
Guan et al. 2013 |
| 43 | "19a" (JAK1, JAK3, CK2&alfa;2, 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 |