Niskocząsteczkowe inhibitory domeny kinazowej JAK2
HEL SET-2 Ba/F3:JAK2wt Ba/F3:JAK2V617F Karpas-1106P 32D| 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,JAK2V617F
Ba/F3:EpoR,JAK2wt HEL |
1.5
10.0 |
Grunberger et al. 2003
Lipka et al. 2008 |
3 | WP1066 | tyrphostin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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, PKCa,b1) |
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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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, 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 |
0.0004 | 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, CaMKIId,g,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 hexabromo cyclohexane low mM 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,CK2a2, 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 | ||||||||||||