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Purity: ≥98%
Acrizanib, formerly known as LHA510, is a novel, potent and selective angiogenesis inhibitor and VEGFR‑2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration.
ln Vitro |
The VEGFR-2 inhibitor acizanib has an IC50 for BaF3-KDR of 17.4 nM. Merely thirteen wild-type kinases were demonstrated to be susceptible to ≤10% residual kinase activity by Acrizanib (Compound 35): CSF1R, Kit, PDGFRα, PDGFRβ, VEGFR1, VEGFR2, VEGFR3, Fms (soluble VEGFR1), DDR1, DDR2, TIE1, and ABL1 (non-phosphorylated) [1].
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ln Vivo |
Studies on the ocular PK of acrizanib in rats revealed notable distinctions from those found with compound 25. The AUC ratio to acrizanib levels in plasma increased significantly (higher in PEC than in plasma at day 11), despite the fact that long-term exposure was evident in PEC once more. Furthermore, 10 days after administration, acrizanib significantly improved, in contrast to 25, the retinal to plasma AUC exposure ratio (598× for acrizanib vs. 0.8× for 25) [1].
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References |
[1]. Adams CM, et al. The Discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for
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Molecular Formula |
C20H18F3N7O2
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Molecular Weight |
445.4062
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Exact Mass |
445.1474
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CAS # |
1229453-99-9
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Related CAS # |
1229453-99-9;
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SMILES |
O=C(N1C=CC2=C1C=CC(OC3=NC=NC(CNC)=C3)=C2)NC4=NN(C)C(C(F)(F)F)=C4
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InChi Key |
XPIHPLVWOUDMPF-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C20H18F3N7O2/c1-24-10-13-8-18(26-11-25-13)32-14-3-4-15-12(7-14)5-6-30(15)19(31)27-17-9-16(20(21,22)23)29(2)28-17/h3-9,11,24H,10H2,1-2H3,(H,27,28,31)
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Chemical Name |
5-({6-[(methylamino)methyl]pyrimidin-4-yl}oxy)-N-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-1H-indole-1-carboxamide
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Synonyms |
Acrizanib LHA510 LHA 510 LHA-510.
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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 : ~41.67 mg/mL (~93.56 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.67 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 20.8 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: ≥ 2.08 mg/mL (4.67 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 20.8 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: ≥ 2.08 mg/mL (4.67 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 | 2.2451 mL | 11.2256 mL | 22.4512 mL | |
5 mM | 0.4490 mL | 2.2451 mL | 4.4902 mL | |
10 mM | 0.2245 mL | 1.1226 mL | 2.2451 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 |
NCT02076919 | Completed Has Results | Drug: LHA510 Ophthalmic Suspension Drug: LHA510 Vehicle |
Age-Related Macular Degeneration | Alcon Research | February 2014 | Phase 1 |
NCT02355028 | Completed Has Results | Drug: LHA510 ophthalmic suspension Drug: LHA510 vehicle |
Exudative Age-Related Macular Degeneration |
Alcon, a Novartis Company | March 3, 2015 | Phase 2 |
A noninvasive topical ocular therapy for the treatment of neovascular or “wet” age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in vivo models of choroidal neovascularization (CNV) as the primary means of developing SAR related to efficacy from topical administration. Ultimately, this effort led to the discovery of acrizanib (LHA510), a small-molecule VEGFR-2 inhibitor with potency and efficacy in rodent CNV models, limited systemic exposure after topical ocular administration, multiple formulation options, and an acceptable rabbit ocular PK profile. td> |