JAK2 inhibitor

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