| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| 25mg | |||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
ROCK2 (IC50 = 10 nM); LIMK2 (IC50 = 1.6 nM); LIMK1 (IC50 = 24 nM); PKA (IC50 = 1 nM)
LX7101 targets LIMK1 (IC₅₀ = 24 nM), LIMK2 (IC₅₀ = 1.6 nM), ROCK2 (IC₅₀ = 10 nM), and PKA (IC₅₀ < 1 nM). It is a pyrrolopyrimidine-based small molecule that acts as a dual inhibitor of LIM-domain kinases and ROCK. The compound also inhibits Akt1 with an IC₅₀ of less than 1 nM. By inhibiting these kinases, LX7101 modulates the actin cytoskeleton and reduces intraocular pressure. |
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| ln Vitro |
LX7101 is a dual inhibitor of ROCK and LIM-kinase used to treat glaucoma and associated ocular hypertension. Additionally, LX-7101 exhibits strong Akt1 inhibition, as evidenced by an IC50 of less than 1 nM[1]. At higher physiological ATP concentrations, LX7101's overall selectivity for LIMK2 increases. LX7101's activity under physiological conditions is mostly brought on by LIMK2 inhibition[2].
In vitro, LX7101 is a potent inhibitor of LIMK1 (IC₅₀ = 24 nM), LIMK2 (IC₅₀ = 1.6 nM), ROCK2 (IC₅₀ = 10 nM), and PKA (IC₅₀ < 1 nM). It also inhibits Akt1 with an IC₅₀ of less than 1 nM. The compound's primary mechanism involves inhibition of LIMK2 under physiological conditions. |
| ln Vivo |
LX-7101 is a glaucoma treatment drug that has advanced to Phase-I clinical trials. It lowers intraocular pressure (IOP). After administration, LX-7101 significantly lowers intracranial pressure in rabbits between one and six hours[1]. The tolerability of LX-7101 topical doses on mice, rats, and rabbits' eyes is assessed. In non-GLP single dose trials, it is well tolerated at doses up to 0.5%. LX-7101 (5%) showed a long duration of action, with IOP not returning to baseline until more than 8 h postdose[2]. In the mouse IOP assay, it achieved additional reduction of IOP (5.0 mmHg total reduction) compared to the 0.1% formulation.
In vivo, LX7101 has been investigated in clinical trials for its efficacy in treating primary open-angle glaucoma and ocular hypertension. It functions as an inhibitor of specific enzymes involved in the regulation of intraocular pressure. The compound's activity as a dual LIMK/ROCK inhibitor makes it effective in reducing intraocular pressure. |
| Enzyme Assay |
Non-cellular enzyme assays for LX7101 involve measuring kinase inhibition using recombinant enzymes. LIMK1, LIMK2, ROCK2, PKA, and Akt1 are incubated with ATP, substrate, and varying concentrations of LX7101. Phosphorylation of the substrate is measured using radioactive or luminescent methods. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular experiments involve treating cells with LX7101 at various concentrations. Kinase inhibition is confirmed by measuring phosphorylation of downstream targets such as cofilin (for LIMK) and myosin light chain (for ROCK) by Western blot. Cell-based assays may also assess the compound's effects on actin cytoskeleton organization and cell migration.
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| Animal Protocol |
In vivo animal studies for LX7101 involve animal models of glaucoma and ocular hypertension. The compound is administered via topical or other appropriate routes. Intraocular pressure is measured over time to assess efficacy. The compound's effects on the ocular drainage system are also evaluated.
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| ADME/Pharmacokinetics |
LX7101 has a molecular weight of 451.52 g/mol and a molecular formula of C₂₃H₂₉N₇O₃. It is a pyrrolopyrimidine-based small molecule. The compound has been investigated in clinical trials for glaucoma and ocular hypertension.
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| Toxicity/Toxicokinetics |
Specific toxicity data for LX7101 is limited. As a kinase inhibitor, it would be expected to have on-target effects related to kinase inhibition. The compound is for research purposes only and should be handled with appropriate safety precautions.
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| References |
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| Additional Infomation |
LX-7101 is being studied in the clinical trial NCT01528111 (a study evaluating the safety, tolerability and efficacy of LX7101 in patients with primary open-angle glaucoma or ocular hypertension).
LX7101 is a potent dual inhibitor of LIMK1/2 and ROCK2 with IC₅₀ values of 24 nM, 1.6 nM, and 10 nM, respectively. It also inhibits PKA and Akt1 with IC₅₀ values of less than 1 nM. The compound is being developed for the treatment of glaucoma and ocular hypertension. This product is for research purposes only and is not for human therapeutic use. |
| Molecular Formula |
C23H30CLN7O3
|
|---|---|
| Molecular Weight |
487.99
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| Exact Mass |
451.233
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| Elemental Analysis |
C, 61.18; H, 6.47; N, 21.71; O, 10.63
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| CAS # |
1192189-69-7
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| Related CAS # |
1192189-69-7;2319882-48-7 (HCl);1192189-70-0 (acetate);1374644-79-7 (besylate);
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| PubChem CID |
56962369
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| Appearance |
White to off-white solid powder
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| LogP |
3.349
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
698
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1(C([H])([H])N([H])[H])C([H])([H])C([H])([H])N(C2C3C(C([H])([H])[H])=C([H])N([H])C=3N=C([H])N=2)C([H])([H])C1([H])[H])N([H])C1C([H])=C([H])C([H])=C(C=1[H])OC(N(C([H])([H])[H])C([H])([H])[H])=O
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| InChi Key |
PWPNYABQEOGNNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H29N7O3/c1-15-12-25-19-18(15)20(27-14-26-19)30-9-7-23(13-24,8-10-30)21(31)28-16-5-4-6-17(11-16)33-22(32)29(2)3/h4-6,11-12,14H,7-10,13,24H2,1-3H3,(H,28,31)(H,25,26,27)
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| Chemical Name |
[3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate
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| Synonyms |
LX-7101; LX 7101; LX7101
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| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~150 mg/mL (~332.2 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (16.61 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 75.0 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: ≥ 7.5 mg/mL (16.61 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 75.0 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: ≥ 7.5 mg/mL (16.61 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 | 2.0492 mL | 10.2461 mL | 20.4922 mL | |
| 5 mM | 0.4098 mL | 2.0492 mL | 4.0984 mL | |
| 10 mM | 0.2049 mL | 1.0246 mL | 2.0492 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01528111 | Completed | Drug: LX7101 (0.125%) Drug: LX7101 (0.25%) |
Primary Open-angle Glaucoma Ocular Hypertension |
Lexicon Pharmaceuticals | March 2012 | Phase 1 Phase 2 |
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