| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
- Compound 16 is a dual inhibitor of ROCK1 (IC₅₀ = 0.017 µM) and ROCK2 (IC₅₀ = 0.002 µM), with high selectivity over PKA (IC₅₀ = 0.24 µM) and broad kinome selectivity. [1]
- Compound 58 is a dual ROCK1 and ROCK2 inhibitor (IC₅₀ = 0.12 µM for ROCK1, 0.014 µM for ROCK2), showing >200-fold selectivity over PKA (IC₅₀ = 3.3 µM). [1] |
|---|---|
| ln Vitro |
- Compound 16 exhibited potent inhibition in a pMYPT1 ELISA cell assay (IC₅₀ = 0.012 µM), confirming its activity as a dual ROCK1/ROCK2 inhibitor in a cellular context. [1]
- Compound 58 showed cellular activity in the pMYPT1 ELISA assay with an IC₅₀ of 0.094 µM. [1] - Broad kinome profiling of Compound 16 against 80 kinases showed >10 µM IC₅₀ for 63 kinases and >1 µM for 10 kinases, with low nanomolar activity only against ROCK1, ROCK2, PKG1A (IC₅₀ = 1 nM), and PKA (IC₅₀ = 47 nM). [1] |
| ln Vivo |
- Compound 16 was tested in an optic nerve crush model in rats. Oral administration at 10 mg/kg once daily for 5 weeks showed significant protection of axons in the retinal nerve fiber layer (RNFL) compared to vehicle control. [1]
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| Cell Assay |
- pMYPT1 ELISA was used as a ROCK-dependent cell-based assay to evaluate compound activity in cells. Cells were treated with compounds and phosphorylation of MYPT1 was measured. [1]
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| Animal Protocol |
- In the optic nerve crush model, Sprague Dawley rats were orally administered Compound 16 at 10 mg/kg once daily for 5 weeks. Retinal nerve fiber layer protection was assessed via immunohistochemical staining for βIII-tubulin positive fibers. [1]
- Pharmacokinetic studies were performed in C57BL6 mice and Sprague Dawley rats with a dose of 10 µmol/kg via IV, IP, and PO administration. Plasma and brain exposure were measured. [1] |
| ADME/Pharmacokinetics |
Compound 16 showed a reasonable half-life (1.5–2.0 h in rats and mice), good plasma and brain tissue exposure, and moderate oral bioavailability (F = 39% in rats, no reported in mice). [1]
Compound 58 showed good solubility (51.2 µM), moderate plasma protein binding (57.1% free), and moderate permeability (PAMPA = 2.5 × 10⁻⁶ cm/s). [1] |
| References | |
| Additional Infomation |
Compound 16 was provided via the AbbVie Compound Toolbox as a tool compound for ROCK1/ROCK2 inhibition studies. [1]
- Cocrystal structure data of Compound 12 with PKA, ROCK1, and ROCK2 guided the design of selective inhibitors that target aspartic acid residues (Asp176 and Asp218) in ROCK2, which correspond to glutamic acid in PKA. [1] - Introducing a piperidine-3-methylamine group yielded Compound 58, which exhibited superior drug-like properties and reduced CYP inhibition. [1] |
| Molecular Formula |
C60H102O29
|
|---|---|
| Molecular Weight |
1287.4345
|
| Exact Mass |
1286.65
|
| CAS # |
1126032-65-2
|
| PubChem CID |
87753664
|
| Appearance |
White to off-white solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Index of Refraction |
1.644
|
| LogP |
1.42
|
| Hydrogen Bond Donor Count |
19
|
| Hydrogen Bond Acceptor Count |
29
|
| Rotatable Bond Count |
20
|
| Heavy Atom Count |
89
|
| Complexity |
2360
|
| Defined Atom Stereocenter Count |
35
|
| SMILES |
C[C@H](CC[C@H](C(C)(C)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@H](O1)CO[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)O)O)O[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)O)O)[C@H]4CC[C@@]5([C@@]4(C[C@H]([C@@]6([C@H]5CC=C7[C@H]6CC[C@@H](C7(C)C)O[C@H]8[C@@H]([C@H]([C@@H]([C@H](O8)CO)O[C@H]9[C@@H]([C@H]([C@@H]([C@H](O9)CO)O)O)O)O)O)C)O)C)C
|
| InChi Key |
SQKPHECGTGXVQW-MRLZYGMXSA-N
|
| InChi Code |
InChI=1S/C60H102O29/c1-23(9-13-35(57(4,5)79)87-55-50(89-54-47(77)42(72)38(68)29(20-63)83-54)43(73)39(69)31(85-55)22-80-51-45(75)40(70)36(66)27(18-61)81-51)24-15-16-58(6)32-12-10-25-26(60(32,8)33(65)17-59(24,58)7)11-14-34(56(25,2)3)86-52-48(78)44(74)49(30(21-64)84-52)88-53-46(76)41(71)37(67)28(19-62)82-53/h10,23-24,26-55,61-79H,9,11-22H2,1-8H3/t23-,24-,26-,27-,28-,29-,30-,31-,32+,33-,34+,35-,36-,37-,38-,39-,40+,41+,42+,43+,44-,45-,46-,47-,48-,49-,50-,51-,52+,53+,54+,55+,58+,59-,60+/m1/s1
|
| Chemical Name |
(2R,3R,4S,5S,6R)-2-[[(2R,3S,4S,5R,6S)-6-[(3R,6R)-6-[(3S,8S,9R,10R,11R,13R,14S,17R)-3-[(2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-11-hydroxy-4,4,9,13,14-pentamethyl-2,3,7,8,10,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-hydroxy-2-methylheptan-3-yl]oxy-3,4-dihydroxy-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
|
| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~77.67 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (1.94 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (1.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7767 mL | 3.8837 mL | 7.7674 mL | |
| 5 mM | 0.1553 mL | 0.7767 mL | 1.5535 mL | |
| 10 mM | 0.0777 mL | 0.3884 mL | 0.7767 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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