rock-in-2

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.

ROCK inhibitor-2 is a selective dual inhibitor of ROCK1 and ROCK2 (IC50s of 17 nM and 2 nM, respectively).

3'-Dephosphocoenzyme A is an intermediate in the biosynthesis of coenzyme A from pantothenic acid .1 It is phosphorylated by CoA synthase in humans to form CoA. 3'-Dephosphocoenzyme A can be used as a transcription initiator in the synthesis of CoA-RNA by in vitro transcription.2,3 References1. Leonardi, R., Zhang, Y.M., Rock, C.O., et al. Coenzyme A: Back in action. Prog. Lipid Res. 44(2-3), 125-153 (2005).2. Huang, F. Efficient incorporation of CoA, NAD and FAD into RNA by in vitro transcription. Nucleic Acids Res. 31(3), e8 (2003).3. Sapkota, K., and Huang, F. Efficient one-pot enzymatic synthesis of dephospho coenzyme A. Bioorg. Chem. 76, 23-27 (2018).

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg/ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg/ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg/kg, respectively). Zonisamide (40 mg/kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).

ROCK2-IN-2 is a selective inhibitor of ROCK2 (IC50 of <1 μM).

Rho-Kinase-IN-2 (Compound 23) is an orally active and selective inhibitor of Rho Kinase (ROCK), which can penetrate the central nervous system (CNS). It exhibits a high affinity for ROCK2 with an inhibition constant (IC50) of 3 nM. This compound is of potential interest for further investigations in the field of Huntington's disease research [1].

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.

1. beta-Asarone (Cis-Isoelemicin) may be a potential preventive drug for Alzheimer's disease. 2. Beta-Asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice. 3. The co-administration of beta-Asarone(Cis-Isoasarone) and l-dopa may contribute to the treatment of 6-OHDA-induced damage in rats by inhibiting autophagy activity. 4. Beta-Asarone exhibits anti-inflammatory effects by suppressing the production of pro-inflammatory mediators through NF-κB signaling and the JNK pathways in activated microglial cells and might be developed as a promising candidate to treat various neuroinflammatory diseases.

Verosudil (AR-12286) is a highly potent Rho kinase (ROCK) inhibitor with a Ki of 2 and 2 nM against ROCK1 and ROCK2, respectively. AR-12286 reverses steroid-induced intraocular pressure in mice by decreasing intraocular pressure by increasing outflow of aqueous ether through the trabecular reticulum.

ROCK-IN-D2 is an effective and selective inhibitor of ROCK.

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Zonisamide sodium is a 1,2 benzisoxazole derivative. It is the first agent of this chemical class to be developed as an antiepileptic drug.