| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
IC50: 0.21 µM (ABHD17B)[1]
ABHD17A, ABHD17B, ABHD17C (alpha/beta hydrolase domain-containing protein 17 family) |
|---|---|
| ln Vitro |
N-Ras depalmitoylation in AML cells is attenuated by ABD957 (500 nM; pretreatment for 1 hour)[1]. NRAS-mutant leukemia cells' signaling and proliferation are inhibited by ABD957 (0.11), 10 μM, and 72 hours[1].
ABD957 has an IC50 of 0.21 uM for ABHD17B. It selectively targets the active-site cysteine residue of ABHD17 enzymes, forming an irreversible covalent bond. It effectively blocks N-Ras depalmitoylation, leading to the inhibition of N-Ras signaling. This results in the suppression of growth in NRAS mutant acute myeloid leukemia (AML) cells. |
| ln Vivo |
In vivo, ABD957 has been shown to block the growth of NRAS-mutant AML cells. By inhibiting ABHD17, it prevents the depalmitoylation and proper localization of NRAS, thereby suppressing the MAPK signaling pathway that drives the proliferation of these cancer cells. It represents a potential targeted therapy for NRAS-mutant cancers.
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| Enzyme Assay |
In a non-cell-based biochemical assay, recombinant human ABHD17B enzyme is incubated with a fluorogenic substrate (e.g., 4-methylumbelliferyl palmitate) in assay buffer (e.g., 50 mM HEPES, pH 7.4, 150 mM NaCl). The test compound (ABD957) is pre-incubated with the enzyme for a period (e.g., 30-60 min) to allow covalent modification. The reaction is then initiated by adding the substrate. Fluorescence intensity (Ex 360 nm, Em 465 nm) is measured continuously to determine the IC50 value.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: OCI-AML3, THP1, HL60, NB-4 and NOMO1 cells Tested Concentrations: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Duration: 72 hrs (hours) Experimental Results: decreased the growth of NRAS-mutant AML cell lines(OCI-AML3, THP1 and HL60), but not KRAS mutant cell lines(NB-4 and NOMO1). For in vitro cell assays, human AML cell lines (e.g., OCI-AML3, THP1, HL60) are treated with various concentrations of ABD957 (0.1-10,000 nM) for 72 hours. Cell viability is measured using a resazurin-based assay or by counting the number of viable cells. The growth of NRAS-mutant cell lines is selectively inhibited, with IC50 values in the low nanomolar range. |
| Animal Protocol |
In a mouse xenograft model, NRAS-mutant AML cells are injected subcutaneously into immunodeficient mice. Once tumors are established, ABD957 is administered, typically via intraperitoneal injection at a dose of 10-50 mg/kg. Tumor volume is measured every 3-4 days. At the end of the study, tumor tissue is collected for Western blot analysis to confirm the inhibition of N-Ras depalmitoylation and downstream signaling (p-ERK).
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| ADME/Pharmacokinetics |
Pharmacokinetic studies have shown that ABD957 has suitable properties for in vivo use, but specific parameters are not publicly available. As a covalent inhibitor, its in vivo activity is dependent not only on its plasma half-life but also on the residence time of the covalent bond. It is typically dosed once or twice daily in animal models to maintain target inhibition.
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| Toxicity/Toxicokinetics |
No formal toxicology studies have been reported for ABD957. As a novel inhibitor of depalmitoylases, its potential toxicities are not fully understood. NRAS is a key oncogene, but it also plays a role in normal cell signaling. Long-term inhibition could have effects on normal tissues, particularly the hematopoietic system. This is a research compound, not a clinical drug.
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| References | |
| Additional Infomation |
N-Ras is one of the most frequently mutated oncogenes in human cancers, particularly in melanomas and leukemias. Direct inhibition of NRAS has proven challenging, making its regulators, like ABHD17, attractive drug targets. ABD957 is a first-in-class chemical probe for studying the biological role of ABHD17. It is for research use only.
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| Molecular Formula |
C27H36F3N7O5S
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|---|---|
| Molecular Weight |
627.68
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| CAS # |
3007772-60-0
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| Appearance |
White to off-white solid powder
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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 :~25 mg/mL (~39.83 mM)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5932 mL | 7.9658 mL | 15.9317 mL | |
| 5 mM | 0.3186 mL | 1.5932 mL | 3.1863 mL | |
| 10 mM | 0.1593 mL | 0.7966 mL | 1.5932 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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