| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
BTK
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|---|---|
| ln Vitro |
LOXO-305 is a highly selective, non-covalent, next generation BTK inhibitor. We previously showed that LOXO-305 potently inhibited both wild-type (WT) BTK and BTK C481S -mediated kinase activity in enzyme and cell-based assays with nanomolar potency, caused regression of BTK-dependent lymphoma mouse xenograft models, and was more than 300-fold selective for BTK over 98% of 370 other kinases tested and showed no significant inhibition of non-kinase off targets at 1 mM (Brandhuber et al. SOHO 2018) [1].
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| ln Vivo |
In addition, ADME and pharmacokinetic experiments in two preclinical species predicted that LOXO-305 will have high human exposure and sustained BTK C481S target coverage in patients at clinically achievable doses[1].
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| Cell Assay |
To assess cellular BTK inhibitor potency, HEK293T cell lines transiently expressing wild-type BTK and BTK C481 substitution mutations were serum starved and incubated with LOXO-305 overnight. Cells were next incubated with serum and orthovanadate for 5 min and the phosphorylated Y223 BTK was analyzed by immunoblot. Bands were quantified and the IC50 values calculated with GraphPad Prism. The equilibrium-binding affinities for targeted BTK inhibitors to BTK enzyme variants were determined by surface plasmon resonance (SPR) using the Biacore T200. Biotinylated BTK variants were immobilized on a docked streptavidin coated sensor chip. Five concentrations of each inhibitor plus blank controls were analyzed. Association/dissociation rate constants were calculated by global fitting of the data to a 1:1 binding interaction model[1].
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| References |
| Molecular Formula |
C22H21F4N5O3
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|---|---|
| Molecular Weight |
479.43
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| Exact Mass |
479.16
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| Elemental Analysis |
C, 55.12; H, 4.42; F, 15.85; N, 14.61; O, 10.01
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| CAS # |
2101700-14-3
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| Related CAS # |
Pirtobrutinib;2101700-15-4
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| PubChem CID |
129269918
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| Appearance |
Typically exists as light yellow to yellow solids at room temperature
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
719
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](C(F)(F)F)N1C(=C(C(=N1)C2=CC=C(C=C2)CNC(=O)C3=C(C=CC(=C3)F)OC)C(=O)N)N
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| InChi Key |
FWZAWAUZXYCBKZ-LLVKDONJSA-N
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| InChi Code |
InChI=1S/C22H21F4N5O3/c1-11(22(24,25)26)31-19(27)17(20(28)32)18(30-31)13-5-3-12(4-6-13)10-29-21(33)15-9-14(23)7-8-16(15)34-2/h3-9,11H,10,27H2,1-2H3,(H2,28,32)(H,29,33)/t11-/m1/s1
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| Chemical Name |
5-amino-3-[4-[[(5-fluoro-2-methoxybenzoyl)amino]methyl]phenyl]-1-[(2R)-1,1,1-trifluoropropan-2-yl]pyrazole-4-carboxamide
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| Synonyms |
R)-Pirtobrutinib; 2101700-14-3; (R)-5-Amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide; SCHEMBL19014260; (R)-LOXO-305; FWZAWAUZXYCBKZ-LLVKDONJSA-N; AKOS040754869;
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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: 200 mg/mL (417.16 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 50.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0858 mL | 10.4291 mL | 20.8581 mL | |
| 5 mM | 0.4172 mL | 2.0858 mL | 4.1716 mL | |
| 10 mM | 0.2086 mL | 1.0429 mL | 2.0858 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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