CCG-100602

Uses

The Rho family of small GTPases play an important role in transduction of cell signaling events associated with several human cancers. CCG-1423 is a specific inhibitor of Rho pathway-mediated signaling and activation of serum response factor (SRF) transcription. The site of inhibition in the pathway is not precisely defined but CCG-1423 appears to act on some aspect of the interaction of SRF with its transcriptional cofactor megakaryoblastic leukemia 1 (MKL1) at a point upstream of DNA binding. CCG-100602 is a CCG-1423 analog developed for improved selectivity, potency, and attenuated cytotoxicity relative to its parent compound. CCG-100602 inhibits RhoA/C-mediated, SRF-driven luciferase expression in PC-3 prostate cancer cells with an IC50 value of 9.8 μM. At 100 μM, CCG-100602 demonstrates 72% inhibition of PC-3 cell invasion into a Matrigel model of metastasis, exhibiting an efficacy:toxicity profile superior to that of CCG-1423 at 10 μM.[Cayman Chemical]

Biological Activity

ccg-100602 is a rho pathway inhibitor.rho, a member of the ras superfamily of small gtp-binding proteins, plays a key role in various biological processes including microtubule dynamics, gene transcription, actin cytoskeleton organization, cell cycle progression, oncogenic transformation, as well as epithelial wound repair.

in vitro

ccg-100602 was developed as a ccg-1423 analog for improved selectivity, potency, and attenuated cytotoxicity. it was found that ccg-100602 was able to inhibit rhoa/c-mediated and srf-driven luciferase expression in pc-3 prostate cancer cells. at 100 μm, ccg-100602 showed 72% inhibition of pc-3 cell invasion into a matrigel model of metastasis, having an superior efficacy-toxicity profile to that of ccg-1423 [1].

in vivo

to evaluate whether inhibition of srf could protect podocytes from hyperglycaemia injury, daily ip administration of ccg-1423 was performed in dm rata. results showed that ccg-1423 could ameliorate proteinuria dose-dependently. ccg-1423 at 0.02 mg/kg could significantly reduce the body weight, compared with the vehicle controls. in addition, the inhibition of srf with ccg-1423 also significantly abrogated the reduction of synaptopodin expression and the induction of srf,α-sma, fsp-1 expression in renal cortex tissues [2].

IC 50

9.8 μm for pc-3 prostate cancer cells

References

[1] evelyn, c. r.,bell, j.l.,ryu, j.g., et al. design, synthesis and prostate cancer cell-based studies of analogs of the rho/mkl1 transcriptional pathway inhibitor, ccg-1423. bioorganic & medicinal chemistry letters 20, 665-672 (2010).
[2] zhao l, wang x, sun l, nie h, liu x, chen z, guan g. critical role of serum response factor in podocyte epithelial-mesenchymal transition of diabetic nephropathy. diab vasc dis res. 2016 jan;13(1):81-92.