TARGETgenehuman
ROCK2 — Rho-associated protein kinase 2
Description
ROCK2 — Rho-associated kinase, druggable by Fasudil (approved in Japan/China for stroke). ROCK1/2 expression elevated in SMND7 mice. Fasudil Phase 2 in ALS (NCT03792490). Part of actin dynamics cascade: SMN-PFN1-RhoA-ROCK-LIMK-CFL2. Nobody has tested ROCK inhibitors in SMA mouse models — first-in-field.
Linked hypotheses (20)
- MN25_ROCK2 binds LIMK2_aC (Boltz-2 iPTM=0.921)targetconf 92%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
- [Survival] LIMK1 is implicated in SMA pathogenesis based on 3 converging claimstargetconf 90%
Top compound hits (10)
| Compound ID | SMILES | Score | Tier |
|---|---|---|---|
| Fasudil | O=C1CCN(Cc2cccc3cnccc23)CC1 | 0.488 | ready |
| CHEMBL128467 | O=S(=O)(O)CCNc1cc2ncnc(Nc3cccc(Br)c3)c2cn1 | 1.276 | promising |
| CHEMBL308645 | Cc1cc(CCC(=O)O)[nH]c1/C=C1\C(=O)Nc2ncnc(Nc3ccc(F)c(Cl)c3)c21 | 1.250 | promising |
| Riluzole | Oc1nc2ccc(OC(F)(F)F)cc2s1 | 1.206 | promising |
| GenMol_100 | O=C1CCN(Cc2csc(-c3ccccc3)n2)CC1 | 1.198 | promising |
| Ripasudil | O=S(=O)(NCC1CC1)c1ccc2[nH]c3c(c2c1)CNC3 | 1.194 | promising |
| CHEMBL409082 | O=C(Nc1nnc(SCc2ccccc2)s1)c1ccc(F)cc1 | 1.191 | promising |
| H-1152 | CC(C)C(=O)N1CCC(C(F)(F)F)CC1c1ccncc1 | 1.185 | promising |
| GenMol_103 | O=C1CCN(Cc2cccnc2-c2ccccc2)CC1 | 1.184 | promising |
| MW150 | Cc1nnc(-c2cccc(-c3cc(C)nn3C)c2)o1 | 1.150 | promising |
Linked claims (50)
| Type | Predicate | Conf | Source |
|---|---|---|---|
| pathway membership | The RHO-1/Rho GTPase-LET-502/ROCK-MLC-4 phosphorylation signaling pathway regulates axon regeneration (observed in C. elegans) | 90% | W2887003161 |
| protein interaction | af3_iptm | 83% | — |
| neuroprotection | Blockade of motor neuron K channels by 4-aminopyridine may prolong the action potential and introduce a significant delay and slowing of evoked synaptic currents (observed in zebrafish model) | 80% | W2120280034 |
| gene expression | fasudil (30 μM) specifically increased glial cell line-derived neurotrophic factor (GDNF) among the secreted proteins at the transcription and secretion levels (in vitro). | 69% | 25185536 |
| drug efficacy | The dual ROCK1/2 inhibitor, fasudil (10 mg/kg), reduced infarct size (mouse model). | 69% | 41704339 |
| drug efficacy | Oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris (clinical). | 69% | 28389592 |
| pathway membership | Activation of the Rho kinase (ROCK) pathway appears to be instrumental for the modulation of the microglial phenotype. | 65% | 28420986 |
| drug efficacy | ROCK inhibition with Y-27632 produced a genotype-specific response, restoring β-catenin nuclear localization exclusively in FlncKO-C2C12 without affecting WT-C2C12 cells (in vitro). | 65% | 41724730 |
| pathway membership | The endoplasmic reticulum-to-Golgi transport of SREBP cleavage-activating protein requires the actin-based cytoskeleton and is enhanced by the Rho-ROCK-LIMK-cofilin pathway. | 65% | 12775580 |
| gene expression | KD025 downregulated the expression of lipogenic factors FABP4 and Glut4 during adipogenesis (in vitro). | 65% | 29410516 |
| pathway membership | Fluid shear stress activates the Rho downstream effectors ROCK, LIM kinase (LIMK), and cofilin. | 65% | 12775580 |
| pathway membership | The ROCK/LIMK/Cofilin pathway is suppressed in rat fibroblasts upon expression of activated Ras (in vitro). | 65% | 16007212 |
| drug efficacy | Inhibiting ROCK by Y-27632 treatment at the zygote stage resulted in most embryos failing to develop to the 8-cell stage (mouse model). | 65% | 24562870 |
| drug efficacy | KD025 dose-dependently reduced infarct volume after transient middle cerebral artery occlusion (mouse model). | 65% | 24466563 |
| drug efficacy | Y27632 (a specific ROCK inhibitor) (in vitro) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. | 65% | 26268695 |
| pathway membership | Activation of the Rho-associated kinase (ROCK) pathway participates in the dopaminergic neuron degeneration and possibly in Parkinson's disease (PD). | 65% | PMID:25908255 |
| drug efficacy | Specific ROCK2 inhibitors (e.g. belumosudil) could be repurposed for cystic kidney disease treatment (in vitro). | 65% | 40253509 |
| drug efficacy | Treatment with Y-27632, a specific ROCK inhibitor, dysregulation of ROCK/cofilin pathway decreased p-cofilin expression and induced cell migration. | 65% | 21769918 |
| drug efficacy | Oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in res... | 65% | 25385601 |
| drug efficacy | Fasudil treatment significantly reduced α-Syn aggregation in vitro in a H4 cell culture model as well as in a cell-free assay. | 65% | 27101974 |
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