Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

Table 1 Single-targeted and multi-targeted inhibitors of cellular tyrosine kinases ABL, SRC and janus kinase family

Inhibitor	Tyrosine kinase target	Neoplasm(s) targeted	Clinical status
Bcr-Abl inhibitors
Imatinib mesylate (STI571)	Bcr-Abl, Kit, PDGFRβ	CML, ALL, GISTs	Approved
Nilotinib (AMN107)	BcrAbl, Kit, PDGFRβ	CML, Pcp ALL, HS, SM	Approved
Tyrphostin AG1024	Bcr-Abl, P-Akt	CML (refract to STI571)	Preclinical
ON012380	Bcr-Abl	CML	Phase I
Tyrphostin AG957	Bcr-Abl	CML	Preclinical
Adaphostin	Bcr-Abl	CML	Preclinical
NS-187	Bcr-Abl, Lyn	CML, Pcp ALL	Preclinical
SRC family inhibitors
Dasatinib (BMS354825)	Bcr-Abl, SRC	Adult CML, Pcp ALL	Approved
SKI-606	Bcr-Abl, SRC	Pcp leukemia, breast	Phase I/II
AZD0530	Bcr-Abl, SRC	Solid tumors	Phase I
		Lung, liver, colorectal	Phase II
TG100435	SRC, Lyn, abl, yes, lck, EphB4	Anti-cancer	Preclinical
PD166326	Bcr-Abl, SRC, lyn	CML	Preclinical
PD180970	Bcr-Abl, SRC, Kit	CML	Preclinical
AZM475271	SRC	Pancreatic	Preclinical
CGP76030	Bcr-Abl, SRC	CML, prost, bone met	Preclinical
PP1	FYN, Lck, Kit, Bcr-Abl	CML	Preclinical
PP2	SRC, Lck, Fyn, Hck	Colon	Preclinical
AP-23236	SRC	Bone metastases	Preclinical
PD173955 + 56	BA, Kit, csk, PDGFRβ, EGFR	CML	Preclinical
SU6656	Scr, Fyn, Yes, Lyn	Lymphoma	Preclinical
CGP77675	SRC	Bone	Preclinical
SU11333 + 36	SRC	Breast, colon	Preclinical
JAK inhibitors
CP-690 550	JAK3	Immunogenic	Preclinical
AG-490	JAK2/3, EGFR	Leukemia, glioma	Preclinical
WHI-P154	JAK3, Hck, Syk	Neural precursor cells	Preclinical
WHI-P131	JAK3	Leukemia, GVHD	Preclinical
WP-1034	JAK, Stat	AML	Preclinical
LFM-A13	JAK2, BTK	Leukemia	Preclinical

BTK: Bruton’s tyrosine kinase; CML: Chronic myeloid leukemia; Pcp: Philadelphia chromosome positive; ALL: Acute lymphoblastic leukemia; GIST: Gastrointestinal stromal tumors; HS: Hypereosinophilic syndrome; SM: Systemic mastocytosis; GVHD: Graft-versus-host disease; Cancer: Several cancer indications; PDGFR: Platelet derived growth factor receptor; EGFR: Epidermal growth factor receptor.