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Chemical Structure| 2095432-71-4 Chemical Structure| 2095432-71-4

Structure of GSK269962A HCl
CAS No.: 2095432-71-4

Chemical Structure| 2095432-71-4

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GSK269962 HCl is a selective ROCK (Rho-associated protein kinase) inhibitor with IC50 values of 1.6 and 4 nM for ROCK1 and ROCK2, respectively.

Synonyms: GSK269962 hydrochloride; GSK269962B; GSK269962

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Product Citations

Product Citations

Lou, Peng ; Liu, Shuyun ; Wang, Yizhuo ; Pan, Cheng ; Xu, Xuewen ; Zhao, Meng , et al.

Abstract: Chronic wounds remain a worldwide clinical challenge, and bioactive materials that can promote skin regeneration are required. Self-assembling peptide (SAP) hydrogels have shown great potential in tissue repair, but their regenerative efficacy and possible mechanism in chronic wound healing are unclear. Here, we report an SAP (KGH) that enhances extracellular matrix (ECM) remodeling and angiogenesis, thereby promoting chronic wound healing in diabetic mice. In vivo, the KGH hydrogel was retained in wounds up to 7 days after injection, and it was effective in speeding up wound closure by ∼20% compared to the control groups and enhancing angiogenesis (e.g., VEGFA, CD31+ capillaries), cell proliferation (e.g., PCNA+ cells), formation of granulation tissue (e.g., α-SMA), and ECM deposition/remodeling (e.g., collagen I, fibronectin). In vitro, the KGH hydrogel created a 3D microenvironment for skin cells, maintained the sustained growth of cell spheroids, and increased the secretion of ECM proteins (e.g., laminin) and growth factors (e.g., PDGFB, VEGFA, and TGF-β) in skin keratinocytes compared to the conventional 2D culture. Mechanistically, the KGH hydrogel might promote wound tissue regeneration by activating the Rho/ROCK and TGF-β/MEK/MAPK pathways. As a type of designed material, SAP can be further re-engineered with biological motifs, therapeutic reagents, or stem cells to enhance skin regeneration. This study highlights that SAP hydrogels are a promising material platform for advanced chronic wound healing and might have translational potential in future clinical applications.

Keywords: Chronic wound ; Self-assembling peptide ; 3D culture ; Extracellular matrix ; Angiogenesis

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Product Details of GSK269962A HCl

CAS No. :2095432-71-4
Formula : C29H31ClN8O5
M.W : 607.06
SMILES Code : O=C(NC1=CC=CC(OC2=CC3=C(N=C(C4=NON=C4N)N3CC)C=N2)=C1)C5=CC=C(OCCN6CCOCC6)C=C5.[H]Cl
Synonyms :
GSK269962 hydrochloride; GSK269962B; GSK269962
MDL No. :MFCD31536773
InChI Key :UYKVMFKKKLLDGL-UHFFFAOYSA-N
Pubchem ID :57398146

Safety of GSK269962A HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of GSK269962A HCl

cytoskeleton

Isoform Comparison

Biological Activity

Description
GSK269962A (GSK 269962) is a potent ROCK inhibitor, which effective against both ROCK1 and ROCK2 isoforms, with IC50 values of 1.6 and 4 nM, respectively. GSK269962A has anti-inflammatory and vasodilatory activities[1].
Target
  • ROCK1

    ROCK1, IC50:1.6 nM

  • ROCK2

    ROCK2, IC50:4 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
OCI-AML3 80 nM 72 hours Inhibited AML cell growth, induced G2 phase arrest and apoptosis Front Pharmacol. 2022 Dec 6;13:1064470.
MV4-11 80 nM 72 hours Inhibited AML cell growth, induced G2 phase arrest and apoptosis Front Pharmacol. 2022 Dec 6;13:1064470.
LepR+ MSCs 1 μM 48 hours Inhibition of ROCK1 signaling pathway, reducing the expression of fibrosis markers Col1a1, vimentin, and α-SMA Cell Commun Signal. 2024 May 6;22(1):257.
UACC62 625nM 48 hours To evaluate the effect of GSK269962A on the proliferation of MAPKi-resistant melanoma cells, showing complete inhibition of proliferation at 625nM concentration. bioRxiv [Preprint]. 2024 Jan 11:2024.01.09.574940.
M481 625nM 48 hours To evaluate the effect of GSK269962A on the proliferation of MAPKi-resistant melanoma cells, showing complete inhibition of proliferation at 625nM concentration. bioRxiv [Preprint]. 2024 Jan 11:2024.01.09.574940.
A375 625nM 48 hours To evaluate the effect of GSK269962A on the proliferation of MAPKi-resistant melanoma cells, showing complete inhibition of proliferation at 625nM concentration. bioRxiv [Preprint]. 2024 Jan 11:2024.01.09.574940.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD-SCID/IL2Rgnull mice AML model Intraperitoneal injection 5 mg/kg and 10 mg/kg 5 days per week for 4 weeks Significantly prolonged mouse survival and reduced leukemia cell infiltration Front Pharmacol. 2022 Dec 6;13:1064470.
Mice PE-induced prostatic hyperplasia model Intraperitoneal injection 5 mg/kg Four times a week for four weeks GSK269962A reduces prostatic stromal hyperplasia and collagen deposition by inhibiting ROCK1 signaling pathway Cell Commun Signal. 2024 May 6;22(1):257.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.65mL

0.33mL

0.16mL

8.24mL

1.65mL

0.82mL

16.47mL

3.29mL

1.65mL

References

 

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