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| 25mg |
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Purity: ≥98%
BQR-695 (previously known as BQR695 or NVP-BQR695) is a potent and selective PI4KIII inhibitor with antimalarial activity . Its IC50 values for the human and Plasmodium variants of PI4KIII are 80 and 3.5 nM, respectively. At a resolution of 3.2, the crystal structure of PI4KIII in complex with the potent anti-malarial drug BQR695 in complex with GDP loaded Rab11 has been determined. Between the central quinoxaline's nitrogen and the amide hydrogen of V598 and the central quinoxaline's amino group and carbonyl of A601, respectively, BQR-695 forms two putative hydrogen bonds with PI4KIII.
| Targets |
Plasmodium; human PI4KIIIβ (IC50 = 80 nM); Plasmodium PI4KIIIβ (IC50 = 3.5 nM)
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| ln Vitro |
Treatment with 0.5 μM of either KAI407 or BQR695 causes GFP-PHOsh2 to redistribute to the parasite plasma membrane, consistent with depletion of intracellular PI4P upon inhibition of PfPI4K function. In addition to inducing a schizont-stage arrest that is identical to that seen in parasites treated with imidazopyrazine, BQR695 exhibits cross-resistance with the imidazopyrazine-resistant lines[2]. It also shows no signs of toxicity against mature red blood cells (RBCs).
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| ln Vivo |
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| Enzyme Assay |
A clonal population of P. falciparum Dd2 parasites is used to initiate two or three independent parasite cultures under the initial selection pressure of 12 nM KAI407, 1 nM KAI715 or 40 nM BQR695. Stepwise drug evolution continues until the final concentration is at least 3-fold higher than the initial concentration (typically 80 to 120 days). For each of the ten resistant strains, copy number variations (CNVs) and single nucleotide variations (SNVs) are detected using a whole-genome tiling array and analyzed with PfGenominator. The susceptibility of each resistant strain to KAI407, KAI715, KDU691 and BQR695 is determined by the 72-hr SYBR Green cell proliferation assay with four independent experiments assayed in duplicate.
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| Cell Assay |
BQR-695 (previously known as BQR695 or NVP-BQR695) is a potent and selective PI4KIIIβ inhibitor with antimalarial activity. It inhibits human PI4KIIIβ and Plasmodium variant of PI4KIIIβ with IC50 values of 80 and 3.5 nM, respectively. The crystal structure of PI4KIIIβ in complex with the potent anti‐malarial compound BQR695 in complex with GDP loaded Rab11 has been solved at a resolution of 3.2 Å. BQR-695 makes two putative hydrogen bonds with PI4KIIIβ, one between the nitrogen of the central quinoxaline and the amide hydrogen of V598, and one between the hydrogen on the amino group off the central quinoxaline with the carbonyl of A601.
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| References |
| Molecular Formula |
C19H20N4O3
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| Molecular Weight |
352.39
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| Exact Mass |
352.15
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| Elemental Analysis |
C, 64.76; H, 5.72; N, 15.90; O, 13.62
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| CAS # |
1513879-21-4
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| Related CAS # |
1513879-21-4
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| PubChem CID |
112499905
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
464
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LYPCULYCGFOIDA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H20N4O3/c1-20-19(24)11-22-18-10-21-14-6-4-12(8-15(14)23-18)13-5-7-16(25-2)17(9-13)26-3/h4-10H,11H2,1-3H3,(H,20,24)(H,22,23)
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| Chemical Name |
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| Synonyms |
NVP-BQR 695; NVP-BQR695; NVP-BQR-695; BQR-695; BQR 695; BQR695
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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: 2.5 mg/mL (7.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8378 mL | 14.1888 mL | 28.3776 mL | |
| 5 mM | 0.5676 mL | 2.8378 mL | 5.6755 mL | |
| 10 mM | 0.2838 mL | 1.4189 mL | 2.8378 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.
Structure of the active site of PI4KIIIβ in the Apo state and bound to the inhibitor BQR695.Protein Sci.2016 Apr;25(4):826-39. |
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HDX‐MS of Rab11 bound to PI4K, and conformational changes in switch regions of Rab11.Protein Sci.2016 Apr;25(4):826-39. |
HDX and structures of PI4KIIIβ bound to GTPγS and GDP loaded Rab11.Protein Sci.2016 Apr;25(4):826-39. |
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