Z BioInf
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 |