TG 100572 Hydrochloride 

TG 100572 Hydrochloride is a multi-targeted kinase inhibitor which inhibits receptor tyrosine kinases and Src kinases; has IC₅₀s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 nM for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, Yes, respectively.

IC50: 2 nM (VEGFR1), 7 nM (VEGFR2), 2 nM (FGFR1), 16 nM (FGFR2), 13 nM (PDGFRβ), 5 nM (Fgr), 0.5 nM (Fyn), 6 nM (Hck), 0.1 nM (Lck), 0.4 nM (Lyn), 1 nM (Src), 0.2 nM (Yes)^[1]

TG 100572 shows sub-nanomolar activity against the Src family as well as RTK such as VEGFR1 and R2, FGFR1 and R2, and PDGFRβ. TG 100572 inhibits vascular endothelial cell proliferation (ED₅₀=610±71 nM) and blocks VEGF-induced phosphorylation of extracellular signal-regulated kinase. TG 100572 induces apoptosis in rapidly proliferating, but not quiescent, endothelial cell cultures^[1]. TG 100572 is shown to inhibit hRMVEC cell proliferation, with an IC₅₀ of 610±72 nM. This suggests that TG 100572 has the therapeutic potential to inhibit VEGF function in ocular endothelial cells, a contributing factor to pathological angiogenesis in diseases such as AMD and PDR^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Systemic delivery of TG 100572 in a murine model of laser-induced choroidal neovascularization (CNV) causes significant suppression of CNV, but with an associated weight loss suggestive of systemic toxicity^[1]. A concentration of 23.4 µM (C_max) of TG 100572 is reached in 30 min (T_max)=0.5 h) in the choroid and the sclera. However, the levels of TG 100572 in the retina are relatively low. The half-life of TG 100572 in ocular tissues is very short; hence, the compound is administered topically minimum t.i.d. to maintain appropriate drug levels in the eye. The maximum concentration one can achieve in formulations using TG 100572 is 0.7% w/v^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

512.43

Solid

C₂₆H₂₇Cl₂N₅O₂

867331-64-4

ClC1=CC=C(O)C=C1C2=CC(C)=C(N=C(NC(C=C3)=CC=C3OCCN4CCCC4)N=N5)C5=C2.Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Doukas J, et al. Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema. J Cell Physiol. 2008 Jul;216(1):29-37.  [Content Brief]

  [2]. Palanki MS, et al. Development of prodrug 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl benzoate (TG100801): a topically administered therapeutic candidate in clinical trials for the treatment of age-rela  [Content Brief]