ROCK2 Inhibitor

LIMK-IN-1 (Compound 14) is an inhibitor of LIM-Kinase (LIMK), with IC₅₀s of 0.5 nM and 0.9 nM for LIMK1 and LIMK2, respectively. LIMK-IN-1 can be used for ocular hypertension and associated glaucoma research.

HSD1590 is potent ROCK inhibitor, with IC₅₀s of 1.22 and 0.51 nM for ROCK1 and ROCK2, respectively. HSD1590 exhibits single digit nanomolar binding to ROCK (K_ds<2 nM). HSD1590 displays low cytotoxicity.

Glycyl H-1152 hydrochloride (compound 18) is a glycyl derivative of Rho-kinase inhibitors H-1152 dihydrochloride. Glycyl H-1152 hydrochloride inhibits ROCKII, Aurora A, CAMKII and PKG, with IC₅₀s of 0.0118, 2.35, 2.57 and 3.26 μM respectively. Glycyl H-1152 hydrochloride has higher selective than H-1152 hydrochloride.

DJ4 is a ATP-competitive inhibitor of ROCK1/2 (IC₅₀ values:5 and 50 nM) and MRCKα/β (IC₅₀ values:10 and 100 nM). DJ4 blocks stress fiber formation and inhibits migration and invasion of cancer cells. DJ4 can be used for study of lung cancer, breast cancer, and pancreatic (PANC-1) cancer.

PF-4950834 is a potent, selective, orally bioavailable, ATP-competitive rho kinase inhibitor with IC₅₀ values of 8.35 nM and 33.12 nM against ROCK2 and ROCK1, respectively. PF-4950834 inhibits neutrophil migration.

Fasudil (HA-1077; AT877) dihydrochloride is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an K_i of 0.33 μM for ROCK1, IC₅₀s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil dihydrochloride is also a potent Ca²⁺ channel antagonist and vasodilator.

ROCK-IN-1 is a potent inhibitor of ROCK, with an IC₅₀ of 1.2 nM for ROCK2.

ROCK2-IN-12 (Compound A25) is a selective ROCK2 inhibitor with an IC₅₀ of 7.0  nM for ROCK2 over ROCK1. ROCK2-IN-12 has potent antifibrotic effects via the TGF-β/Smad and ROCK2/STAT3 signaling pathways. ROCK2-IN-12 significantly reduces collagen deposition and reverses fibrotic progression in Bleomycin (HY-108345)-induced pulmonary fibrosis (PF) mouse models. ROCK2-IN-12 can be used for lung diseases like pulmonary fibrosis research.

RKI-1313 is a ROCK inhibitor with IC₅₀s of 34, 8 µM for ROCK 1 and ROCK 2, respectively. RKI-1313 shows little effect on the phosphorylation levels of ROCK substrates, migration, invasion or anchorage-independent growth.

ROCK/HDAC-IN-2 (Compound C-9) is a ROCK/HDAC inhibitor, with IC₅₀ values of 0.185 µM, 0.8 µM, and 0.7 µM for HDAC6, ROCK1, and ROCK2, respectively. ROCK/HDAC-IN-2 can induce apoptosis and changes in mitochondrial membrane potential in cancer cells, demonstrating significant antitumor activity. ROCK/HDAC-IN-2 can be used in the research of pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).

Fasudil (HA-1077; AT877) hydrochloride semihydrate is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an K_i of 0.33 μM for ROCK1, IC₅₀s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil hydrochloride semihydrate is also a potent Ca²⁺ channel antagonist and vasodilator.

ROCK2-IN-11 (Compound A20) is a selective ROCK2 inhibitor with an IC₅₀ of 0.18 μM for ROCK2 over ROCK1. ROCK2-IN-11 can be used for idiopathic pulmonary fibrosis and cGVHD research.

ROCK/HDAC-IN-1 (Compound 10h) is an orally active ROCK/HDAC inhibitor. ROCK/HDAC-IN-1 inhibits ROCK1/2 (IC₅₀: 254.9 nM, 58.18 nM) and HDAC1/2/3/6/8 (IC₅₀: 9.09, 8.03, 6.26, 0.41, 7.69 nM). ROCK/HDAC-IN-1 stimulates the activation of DAMPs, specifically Calreticulin (CRT) exposure and HMGB1 release, indicating that it is a potential ICD inducer.. ROCK/HDAC-IN-1 has antiproliferative activity against breast cancer cells (IC₅₀: 0.37 μM for MDA-MB-231 cell), and inhibits tumor growth and activates T cells without apparent toxicity.

Verosudil (AR-12286) hydrochloride is the hydrochloride form of Verosudil (HY-16758). Verosudil hydrochloride is a ROCK inhibitor. Verosudil hydrochloride has equal inhibitory activity against ROCK1 and ROCK2 (K_i: 2 nM). Verosudil hydrochloride is less selective for PKA, PKCT, MRCKA, and CAM2A (K_i: 69 nM, 9322 nM, 28 nM, 5855 nM, respectively). Verosudil hydrochloride increases trabecular outflow capacity to reduce intraocular pressure. Verosudil hydrochloride is useful in the study of glaucoma and ocular hypertension.

ROCK2-IN-9 (compound 7u) is a selective ROCK2 inhibitor (IC₅₀=36.8 nM) with anticancer activity. ROCK2-IN-9 inhibits cancer cell migration and invasion by regulating multiple cellular activities of the actin cytoskeleton. ROCK2-IN-9 can be used in breast cancer research.

LASSBio-2382 is a dual ROCK1/ROCK2 inhibitor with ROCK1 IC₅₀ of 0.005 μM and ROCK2 IC₅₀ of 0.003 μM. LASSBio-2382 inhibits viability and migration of cancer cells. LASSBio-2382 can be used for the research of triple-negative breast cancer.

KD025m1 is a novel selective ROCK2 inhibitor. KD025m1 has good anti obesity, improved insulin sensitivity, and blood glucose control effects. KD025m1 can be used to study metabolic diseases such as diabetes and obesity.

ROCK2-IN-15 (2-11) is a ROCK2 inhibitor with selective activity against Rho-kinase mediated phosphorylation of myosin light chain phosphates .ROCK2-IN-15 can be used for the research of cardiovascular diseases, pulmonary diseases, inflammatory diseases, neurological diseases, proliferative diseases .

ROCK2-IN-13 is a selective ROCK2 inhibitor. ROCK2-IN-13 reduces nuclear expression by disrupting the interaction of ROCK2 with transcriptional co activators p300> and PGC 1α, repressing oncogenic transcription. ROCK2-IN-13 activates FOXO1 driven PTEN expression, leading to suppression of the PI3K/Akt pathway, induction of G₂/M cell cycle arrest, and promotion of apoptosis. ROCK2-IN-13 ablates the nuclear transcriptional function of ROCK2 that sustains oncogenic signaling and restores the tumor suppressive PTEN/FOXO1 axis. ROCK2-IN-13 can be used for prostate cancer reseach.

ROCK2-IN-20 is a selective ROCK2 inhibitor with an IC₅₀ value of 12 nM. ROCK2-IN-20 can be used for research on multiple sclerosis, pulmonary arterial hypertension, and glaucoma.