NRL-1049
Based on 1 Customer Validation
NRL-1049 (BA-1049 (free base)) is an orally available and selective ROCK2 inhibitor with IC50 values of 0.59 µM for ROCK2 and 26 µM for ROCK1, respectively. NRL-1049 modulates ROCK signaling, preserves blood-brain barrier integrity, reduces edema, seizures and hemorrhage, and alleviates cerebral cavernous malformation lesion burden. NRL-1049 can be used for the study of acute brain injury, ischemic stroke, and cerebral cavernous malformations.
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- Pureté : 99.96%
- CAS No.: 1973494-16-4
- Formule: C16H21N3O2S
- Masse moléculaire:319.42
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[1]|
ROCK1 26 μM (IC50) |
ROCK2 0.59 μM (IC50) |
In Vitro
NRL-1049 potently and selectively inhibits purified recombinant ROCK2, with an IC50 of 0.59 μM, and is 43-fold more selective for ROCK2 than ROCK1[1].
NRL-1049 (10 μM) inhibits ROCK1, ROCK2, and eight additional human protein kinases by greater than 95%[1].
NRL-1049 (0.01-1000 μM; 1 hour prior to LPA stimulation) concentration-dependently inhibits LPA-induced ROCK activity (measured via MLC2 phosphorylation) in hBMVECs, with an EC50 of 26.3 μM after 1 hour of pre-incubation[1].
NRL-1049 (50 μM; 1 hour incubation) inhibits LPA-induced ROCK activity in HUVECs by 15% after 1 hour of incubation, with the effect fully reversed within 1 hour of compound washout[1].
NRL-1049 (1 μM) leads to mouse, cynomolgus monkey, and human hepatocytes producing the active metabolite NRL-2017, rat hepatocytes producing NRL-2017 and an inactive N-oxide metabolite, and dog hepatocytes producing no detectable metabolites[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
NRL-1049 (10 mg/kg; i.p.; single dose 15 minutes post-reperfusion) significantly reduces Evans Blue extravasation, lowers the incidence of hemorrhagic transformation to 25%, and improves hemorrhage grade, preserving blood-brain barrier integrity after transient MCAO in spontaneously hypertensive rats[1].
NRL-1049 (1 mg/kg; p.o.; daily; 3-4 months) reduces CCM lesion burden and hemorrhage in CCM knockout mice, with sustained retention in vascular tissues[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male and female, 18-22 gram, cortical cryoinjury-induced acute brain injury)[1]
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Dosage:10 mg/kg plus 10 mg/h (brain water content, seizure monitoring); 20 mg/kg plus 100 mg/kg/day (Evans Blue extravasation)
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Administration:i.p. (single dose immediately post-injury); s.c. (continuous via osmotic pump, 24 hours); oral (via drinking water, starting immediately post-injury)
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Result:Prevented seizure development to 0% within 24 hours post-injury.
Showed significantly lower ipsilesional brain water content at 24 hours post-injury, with a strong trend toward lower water content as early as 1 hour post-injury.
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Animal Model:Spontaneously hypertensive rats (SHR) (male, 170-300 gram, transient middle cerebral artery occlusion-induced ischemic stroke)[1]
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Dosage:10 mg/kg
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Administration:i.p. (single dose 15 minutes post-reperfusion)
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Result:Significantly reduced Evans Blue extravasation in the ischemic hemisphere compared to vehicle controls.
Reduced incidence of hemorrhagic transformation to 25% compared to 78% of vehicle-treated rats.
Achieved a significantly lower mean hemorrhage grade (0.43).
Chemical Information
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CAS No. 1973494-16-4
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Appearance Solid
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Masse moléculaire 319.42
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Formule C16H21N3O2S
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Color White to off-white
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SMILES
C[C@H](C1CCN(CC1)S(=O)(C2=C3C=CN=CC3=CC=C2)=O)N
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Synonyms
BA-1049 free base
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (313.07 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureté et documentation
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Fiche technique (277 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Mulder IA, et al. The novel ROCK2 selective inhibitor NRL-1049 preserves the blood-brain barrier after acute injury. J Cereb Blood Flow Metab. 2024;44(11):1238-1252. [Content Brief]
[2]. Madden S, et al. Safety, Tolerability, and Pharmacokinetics of NRL-1049, a Rho-Associated Kinase Inhibitor, in Healthy Volunteers: A Phase 1, First-in-Human, Single-Ascending Dose, Randomized, Placebo-Controlled Trial. CNS Drugs. 2025;39(9):865-877. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 3.1307 mL | 15.6534 mL | 31.3067 mL | 78.2669 mL |
| 5 mM | 0.6261 mL | 3.1307 mL | 6.2613 mL | 15.6534 mL | |
| 10 mM | 0.3131 mL | 1.5653 mL | 3.1307 mL | 7.8267 mL | |
| 15 mM | 0.2087 mL | 1.0436 mL | 2.0871 mL | 5.2178 mL | |
| 20 mM | 0.1565 mL | 0.7827 mL | 1.5653 mL | 3.9133 mL | |
| 25 mM | 0.1252 mL | 0.6261 mL | 1.2523 mL | 3.1307 mL | |
| 30 mM | 0.1044 mL | 0.5218 mL | 1.0436 mL | 2.6089 mL | |
| 40 mM | 0.0783 mL | 0.3913 mL | 0.7827 mL | 1.9567 mL | |
| 50 mM | 0.0626 mL | 0.3131 mL | 0.6261 mL | 1.5653 mL | |
| 60 mM | 0.0522 mL | 0.2609 mL | 0.5218 mL | 1.3044 mL | |
| 80 mM | 0.0391 mL | 0.1957 mL | 0.3913 mL | 0.9783 mL | |
| 100 mM | 0.0313 mL | 0.1565 mL | 0.3131 mL | 0.7827 mL |
NRL-1049 Related Classifications
HY-162596 Related Classifications
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