rho 1

Rho-Kinase-IN-1 is an inhibitor of ROCK with Kis of 30.5 nM and 3.9 nM for ROCK1 and ROCK2, respectively. Rho-Kinase-IN-1 can be used in studies about excessive cell proliferation, remodeling, edema and inflammation diseases.

Chroman 1 is an inhibitor of ROCK2 (IC50: 1 nM).

CCG-257081 (MRTF SRF-IN-1) is an inhibitor of cardiac myosin-related transcription factor and serum response factor (MRTF SRF) that acts by inhibiting the Rho MRTF SRF pathway.CCG-257081 has shown efficacy in preventing bleomycin-induced fibrosis in several mouse models. CCG-257081 can be used in cancer prevention and fibrosis research.

Fasudil (HA-1077) is a potent inhibitor of ROCK1, PKA, PKC, and MLCK.

Conopeptide rho-TIA, a peptide from Conus tulipa venom, acts as a selective, noncompetitive inhibitor at the human α1B-Adrenergic Receptor and as a competitive inhibitor at the α1A and α1D-Adrenergic Receptors. Binding to these subtypes, conopeptide rho-TIA may inform the creation of new α1-Adrenergic Receptor subtype-selective drugs [1].

Rho-Kinase-IN-2 (Compound 23) is an orally active and selective inhibitor of Rho Kinase (ROCK) with CNS penetration, exhibiting a high affinity for ROCK2 with an IC50 of 3 nM. This compound is of potential interest for further investigations in Huntington's disease research [1].

1. Methylophiopogonanone B (MOPB) induces cell morphological change and Rho activation via melanocyte dendrite retraction and stress fiber formation.

Promotes proteasomal degradation of Miro1 (mitochondrial Rho GTPase 1). Reduces Miro1 levels in fibroblasts from Parkinson's disease (PD) patients (IC50 = 7.8 μM). Exhibits no significant effect on related outer mitochondrial membrane protein Mitofusin. Reduces stress-induced degeneration of dopaminergic neurons derived from PD patient iPSCs. Rescues age-dependent neuronal loss and prolongs lifespan in fly PD models.

PKN1 2-IN-1 is a potent and selective PKN2 inhibitor with 14-fold higher selectivity for PKN2 than PKN1, membrane permeability and anticancer potential.Protein kinase N proteins (PKN1, PKN2 and PKN3) are effectors of Rho GTPases and are critical for survival in several tumor cell lines including prostate and breast cancer.

Netarsudil, also known as AR-11324, is a Rho-associated protein kinase inhibitor. Netarsudil is potential useful for treating glaucoma and or reducing intraocular pressure. Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms. Netarsudil inhibited kinases ROCK1 and ROCK2 with a Ki of 1 nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC50s of 79 and 16 nM, respectively, and blocked the profibrotic effects of TGF-β2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24 h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect.

CCG-203971 is an inhibitor of SRE activation in the prostate cancer cell line PC-3 (IC50: 6.4 μM), with 87% inhibition of SRE activation achieved at 100 μM. This compound also inhibits PC-3 cell migration (IC50: 4.2 μM), as determined by a scratch wound assay. CCG-203971(CCG203971) causes no cytotoxicity when evaluated by the WST-1 assay. It is well tolerated in normal mice up to doses of 100 mg kg given intraperitoneally over five days.

GSK180736A is an effective and selective GRK2 inhibitor (IC50: 0.77 μM) and >100-fold selectivity over other GRKs. It is a weak inhibitor of PKA (IC50: 30 μM), but highly effective against ROCK1 (IC50: 100 nM).

LX7101 is a potent inhibitor of both LIM kinase (LIMK) 1 and 2, and Rho-associated kinase 1 (ROCK1) and ROCK2, with IC50 values of 32, 4.3, 69, and 32 nM, respectively. It is selective, demonstrated by its lack of cross-reactivity in a panel of binding assays involving 78 receptors, transporters, and an additional 430 kinases, at a concentration of 10 μM. The topical administration of LX7101 (3 μl of a 1 mg ml solution) to the eye has been shown to reduce intraocular pressure in a dexamethasone-induced mouse model of glaucoma.

IMM-01 is a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division. GTP-bound Rho activates mDia family members by disrupting the interaction between the DID and DAD autoregulatory domains, which releases the FH2 domain to modulate actin and microtubule dynamics[1].

Phenylpyropene A is a fungal metabolite originally isolated from P. griseofulvum that has enzyme inhibitory and insecticidal activities.1,2,3 It inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 0.8 μM).1 Phenylpyropene A inhibits diacylglycerol acyltransferase (DGAT) in rat liver microsomes (IC50 = 78.7 μM). It induces mortality in 100% of M. persicae when used at a concentration of 5 ppm.3 |1. Kwon, O.E., Rho, M.C., Song, H.Y., et al. Phenylpyropene A and B, new inhibitors of acyl-CoA: Cholesterol acyltransferase produced by Penicillium griseofulvum F1959. J. Antibiot. (Tokyo) 55(11), 1004-1008 (2002).|2. Lee, S.W., Rho, M.C., Choi, J.H., et al. Inhibition of diacylglycerol acyltransferase by phenylpyropenes produced by Penicillium griseofulvum F1959. J. Microbiol. Biotechnol. 18(11), 1785-1788 (2008).|3. Horikoshi, R., Goto, K., Mitomi, M., et al. Identification of pyripyropene A as a promising insecticidal compound in a microbial metabolite screening. J. Antibiot. (Tokyo) 70(3), 272-276 (2017).

This novel compound is an orally bioavailable antagonist of P2X3 P2X2 3 receptors, exhibiting potent activity with a pIC50 of 8 in both human and rat, and a pIC50 of 7.3 specifically for the human P2X2 3 receptor. It demonstrates high brain penetration, evidenced by a brain to plasma ratio of 6, and effectively blocks agonist-evoked intracellular Ca2+ flux and inward currents within the nanomolar range (10 nM to 1 µM) in cell lines that express human P2X3 and P2X2 3 receptors recombinantly. The compound also shows favorable pharmacokinetic properties, with a half-life (t1 2) of 1.63 hours and a time to reach maximum concentration (Tmax) of 30 minutes.

ROCK-IN-2 (Azaindole 1) is a selective and ATP-competitive ROCK inhibitor with IC50 of 0.6 and 1.1 nM for human ROCK-1 and ROCK-2.

1. Coptisine (Coptisin) treatment increases cell viability based on its reversal effect on the enhanced activity of Indoleamine 2, 3-dioxygenase . 2. Coptisine treats myocardial I R likely through suppressing myocardial apoptosis and inflammation by inhibiting the Rho ROCK pathway. 3. Coptisine is a potential anti-osteosarcoma drug candidate, via exerting a strong anti-osteosarcoma effect with very low toxicity . 4. Coptisine with a high dosage could inhibit cholesterol synthesis via suppressing the HMGCR expression and promoting the use and excretion of cholesterol via up-regulating LDLR and CYP7A1 expression. 5. Coptisine suppresses adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function for breast cancer.

Rhosin hydrochloride is a specific inhibitor of the RhoA subfamily Rho GTPases and inhibits the RhoA-GEF interaction. Rhosin hydrochloride can significantly induce cell apoptosis without affecting cell cycle progression. [1]

DCP-Rho1 is a fluorescent probe for the detection of sulfenic acid-containing proteins.1,2 It displays excitation/emission maxima of 560/581 nm, respectively, and has been used to visualize protein oxidation sites in situ. |1. Klomsiri, C., Rogers, L.C., Soito, L., et al. Endosomal H2O2 production leads to localized cysteine sulfenic acid formation on proteins during lysophosphatidic acid-mediated cell signaling. Free Rad. Biol. Med. 71, 49-60 (2014).|2. Holmila, R.J., Vance, S.A., Chen, X., et al. Mitochondria-targeted probes for imaging protein sulfenylation. Sci. Rep. 8(1), 6635 (2018).

CCG-232964 is an orally active Rho MRTF SRF inhibitor that suppresses LPA-induced CTGF gene expression [1].

SAR407899 is Rho kinase inhibitor potently inhibits endothelin-1-induced constriction of renal resistance arteries.