| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
Aurora kinase inhibitor III, a 2,4-dianilinopyrimidine compound, is a novel, potent, highly selective, cell-permeable and ATP-competitive inhibitor of aurora related kinase (ARK) with IC50 of 42 nM for Aurora A kinase. With IC50 values of 386, 3,550, 591, 1,980, 2,510, 887, and >10,000 nM, respectively, it is more selective for Aurora A than for BMX, BTK, IGF-1R, c-Src, TRKB, SYK, and EGFR. Numerous tumor types have been studied using aurora kinase inhibitor III. Human and mouse c-myc driven B-cell lymphomas have higher levels of Aurora kinase proteins; research into the inhibition of these proteins may result in novel therapeutic approaches for cancer.
| Targets |
Aurora A (IC50 = 42 nM)
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| ln Vitro |
The compound is a 2,4-dianilinopyrimidine analog. The structure-activity relationship (SAR) of analogs is presented: Compound 1 (X=C, Y=N, Z=N) inhibits Aurora A with an IC50 of 42 nM. Compound 2 (X=N, Y=C, Z=N), a regioisomer, shows reduced potency (IC50 931 nM). Compound 3 (X=N, Y=N, Z=C), a 4,6-disubstituted pyrimidine, shows very weak inhibition of Aurora A (IC50 >10,000 nM).[1]
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| References | |
| Additional Infomation |
The 2.25 Å resolution crystal structure of the complex of Aurora A kinase and Aurora kinase inhibitor III was resolved. The inhibitor binds to the ATP-binding pocket in an s-cis conformation. [1]
This binding mode is novel. The dipyrimidine and aniline moieties mimic adenine, forming two hydrogen bonds with the backbone of hinge region A213. The cyclopropylamide moieties face the solvent-exposed region and interact with the carbonyl group of P214 and the side chain of R137 via hydrogen bonds. The trifluoromethyl group interacts with the backbone of G142 and the side chain of K143 in the p ring. [1] Compared to other Aurora A structures, this binding induces conformational changes in the p ring and the DFG motif. The p ring is shifted, and K143 moves and interacts with the trifluoromethyl group of the inhibitor. The conformation of the DFG motif differs from the active (DFG-in) and inactive (DFG-out) states observed in other structures, but is closer to the active form. [1] Unlike inhibitors such as VX-680 (whose similar groups are deeply bound near the DFG motif), the cyclopropylamide group in this compound is exposed in the solvent, which may explain its low kinase selectivity. Analysis suggests that extending the molecule at the trifluoromethyl site to allow it to interact more deeply with the DFG region may improve selectivity for Aurora A. [1] Structural analysis explains the structure-activity relationship: the reduced potency of compound 2 may be due to the breaking of the hydrogen bond with A213. The significant reduction in potency of compound 3 may be due to the need for greater energy to form the cis conformation required for hinge binding. [1] |
| Molecular Formula |
C21H18F3N5O
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| Molecular Weight |
413.4
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| Exact Mass |
413.146
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| Elemental Analysis |
C, 61.01; H, 4.39; F, 13.79; N, 16.94; O, 3.87
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| CAS # |
879127-16-9
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| Related CAS # |
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| PubChem CID |
9549303
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| Appearance |
White to off-white solid powder
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| LogP |
5.475
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
586
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1CC1)NC1C=C(NC2N=C(NC3C=C(C(F)(F)F)C=CC=3)C=CN=2)C=CC=1
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| InChi Key |
RDTDWGQDFJPTPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18F3N5O/c22-21(23,24)14-3-1-4-15(11-14)26-18-9-10-25-20(29-18)28-17-6-2-5-16(12-17)27-19(30)13-7-8-13/h1-6,9-13H,7-8H2,(H,27,30)(H2,25,26,28,29)
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| Chemical Name |
N-[3-[[4-[3-(trifluoromethyl)anilino]pyrimidin-2-yl]amino]phenyl]cyclopropanecarboxamide
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| Synonyms |
Aurora Kinase Inhibitor III; AKI-7169; AKI7169; AKI 7169
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.03 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 (5.03 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 (5.03 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 | 2.4190 mL | 12.0948 mL | 24.1896 mL | |
| 5 mM | 0.4838 mL | 2.4190 mL | 4.8379 mL | |
| 10 mM | 0.2419 mL | 1.2095 mL | 2.4190 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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