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10mg | ||
25mg | ||
50mg | ||
100mg | ||
250mg |
Purity: ≥98%
SNIPER(ABL)-024 is a compound by conjugating GNF5 (an ABL inhibitor) to LCL161 derivative (IAP-inhibitor of apoptosis protein ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 5μM.Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate the BCR-ABL protein.
References |
Cancer Sci.2017 Aug;108(8):1657-1666.
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Molecular Formula |
C52H61F3N8O9S
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Molecular Weight |
1031.14916205406
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CAS # |
2222355-77-1
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SMILES |
O=C(NCCOCCOCCOCCOC1=CC(C(C2=CSC([C@H]3N(C([C@H](C4CCCCC4)NC([C@H](C)NC)=O)=O)CCC3)=N2)=O)=CC=C1)C5=CC=CC(C6=NC=NC(NC7=CC=C(OC(F)(F)F)C=C7)=C6)=C5
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Synonyms |
SNIPER(ABL)-024; SNIPER(ABL) 024
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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 Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 0.9698 mL | 4.8490 mL | 9.6979 mL | |
5 mM | 0.1940 mL | 0.9698 mL | 1.9396 mL | |
10 mM | 0.0970 mL | 0.4849 mL | 0.9698 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.
SNIPER(ABL)‐39 shows potent protein knockdown activity. (a) Chemical structures of SNIPER(ABL) with different linker length. (b) Effect of linker length on the protein knockdown activity of the SNIPER(ABL).(c) Dose response of the protein knockdown activity of SNIPER(ABL)‐39.(d) Binding affinities of SNIPER(ABL)‐39 to ABL and IAP. SNIPER(ABL)‐39 inhibits proliferation of chronic myelogenous leukemia (CML) cells expressing native BCR‐ABL.Cancer Sci.2017 Aug;108(8):1657-1666. th> |
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SNIPER(ABL) composed of various ABL inhibitors and IAP ligands. (a) Chemical structures of SNIPER(ABL). (b–e) The protein knockdown activities of imatinib‐conjugated (b), GNF5‐conjugated (c), HG‐7‐85‐01‐conjugated (d) and dasatinib‐conjugated SNIPER(ABL) (e) were evaluated.K562 cells were incubated with the indicated concentration of SNIPER or ligands mix (LM; indicated ABL inhibitor and IAP ligand) for 6h. Numbers below the ABL panel represent BCR‐ABL/GAPDH or BCR‐ABL/β‐tubulin ratio normalized by vehicle control as 100. (f) List of SNIPER(ABL) compounds and their DC50values. The upper name represents the code number of the SNIPER(ABL) and the lower number shows the concentration of SNIPER(ABL) required to reduce BCR‐ABL protein by 50% (DC50, nM).Cancer Sci.2017 Aug;108(8):1657-1666. td> |
Involvement of ubiquitin and IAP in SNIPER(ABL)‐39‐induced degradation of BCR‐ABL protein.(a) Turnover of BCR‐ABL proteins after SNIPER(ABL)‐39 treatment.(b) Expression ofBcr‐AblmRNA in K562 cells. (c) Effect of ubiquitin activating enzyme inhibitor MLN7243 on protein knockdown activity of SNIPER(ABL)‐39 in K562 cells. (d) Silencing of both cIAP1 and XIAP expression attenuates SNIPER(ABL)‐39‐dependent BCR‐ABL protein degradation. SNIPER(ABL)‐39 inhibits the BCR‐ABL‐related signaling pathway.K562 cells were incubated with the indicated concentration of SNIPER(ABL)‐39 or dasatinib for 6h. pBCR‐ABL, pSTAT5 and pCrkL stand for phosphorylated BCR‐ABL, STAT5 and CrkL, respectively.Cancer Sci.2017 Aug;108(8):1657-1666. td> |