| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
NONO[1]
NONO (non-POU domain-containing octamer-binding protein). (S)-SKBG-1 is the S-enantiomer of the covalent ligand SKBG-1, designed to target the RNA-binding protein NONO. It is classified as an inactive covalent NONO ligand, failing to productively engage NONO Cys145, and is used as an assay control in stereoselective studies investigating NONO modulation and protein degradation mechanisms in cancer cells. |
|---|---|
| ln Vitro |
In vitro, (S)-SKBG-1 displays no significant target engagement or functional inhibition. At 20 uM, it does not suppress androgen receptor (AR) mRNA or protein expression, nor does it inhibit cancer cell proliferation. RNA-seq studies in 22Rv1 cells treated with (S)-SKBG-1 (20 uM, 4 h) show minimal transcriptomic changes compared to active (R)-SKBG-1. Cysteine-directed ABPP confirms that (S)-SKBG-1 fails to engage NONO Cys145, establishing its role as an inactive negative control.
|
| ln Vivo |
In rodent models, (S)-SKBG-1 shows lower potency, requiring higher doses (generally 5-20 mg/kg) to elicit detectable effects on behavior and cognitive function, while maintaining acceptable tolerability and CNS exposure. In xenograft models, (S)-SKBG-1 treatment results in minimal tumor growth suppression, consistent with its inactivity as a NONO-targeting PROTAC ligand, confirming its utility as a negative stereochemical control in vivo.
|
| Enzyme Assay |
Measure target engagement using cysteine-directed activity-based protein profiling (ABPP) in live cells. Treat cells with (S)-SKBG-1 (20 uM, 6 h), then lyse and label remaining free cysteines with a rhodamine-tagged alkyne probe. Resolve samples by SDS-PAGE and visualize in-gel fluorescence. Minimal labeling reduction indicates lack of target engagement. Alternatively, use biotin-alkyne probes for enrichment and MS-based identification. Competition experiments with active (R)-SKBG-1 confirm stereoselectivity.
|
| Cell Assay |
Treat 22Rv1 cells (or other NONO-expressing cancer cell lines) with (S)-SKBG-1 at concentrations up to 20 uM for 24-48 hours. Include DMSO vehicle control and active (R)-SKBG-1 as positive comparator. Assess cell viability using CellTiter-Glo after 4-6 days of treatment. Evaluate AR-FL and AR-V7 mRNA levels by qPCR and protein expression by Western blot. Use sgNONO knockout cells to confirm NONO-dependent effects. Fluorescence microscopy for NONO nuclear foci localization can be performed after 2-24 h treatment.
|
| Animal Protocol |
For in vivo efficacy studies, administer (S)-SKBG-1 to tumor-bearing mice (e.g., 22Rv1 xenografts) via intraperitoneal or oral route at doses of 5-20 mg/kg. For pharmacokinetic studies, collect plasma samples at predetermined time points and analyze compound concentration by LC-MS/MS. Prepare dosing formulations with DMSO/PEG300/Tween 80/saline (10:40:5:45). Assess tumor volume, body weight, and tissue distribution. Compare effects with active (R)-SKBG-1 to validate stereoselective target engagement and inactivity in disease models.
|
| ADME/Pharmacokinetics |
(S)-SKBG-1 has a molecular weight of 495.98 g/mol and a molecular formula of C22H26ClN3O6S. It is soluble in DMSO at 100 mg/mL (~201.62 mM). The compound is stable as powder at -20degC for 3 years and at -80degC in solvent for 6 months. For in vivo formulation, it can be prepared in DMSO:PEG300:Tween 80:saline (10:40:5:45). In rodent models, higher doses (5-20 mg/kg) are typically required to achieve detectable CNS exposure and systemic circulation.
|
| Toxicity/Toxicokinetics |
According to available safety data, (S)-SKBG-1 is not classified as a hazardous substance or mixture. Under fire conditions, it may decompose and emit toxic fumes (including hydrogen chloride, carbon monoxide, and nitrogen oxides). Standard laboratory safety precautions should be followed, including wearing protective gloves and lab coats. The compound is intended for research use only and not for human consumption or therapeutic use.
|
| Additional Infomation |
(S)-SKBG-1 (CAS: 2955618-24-1) is the inactive S-enantiomer of SKBG-1 developed by the Cravatt laboratory (Scripps Research) as a matched negative control for the active NONO-targeting covalent ligand (R)-SKBG-1. It is cataloged as a PROTAC target protein ligand and widely used in target validation, structure-activity relationship (SAR) studies, and stereoselectivity analysis in CNS-active drug development. The compound is for research use only and has not entered clinical trials or received regulatory approval for therapeutic use.
|
| Molecular Formula |
C22H26CLN3O6S
|
|---|---|
| Molecular Weight |
495.98
|
| Exact Mass |
495.123
|
| CAS # |
2955618-24-1
|
| PubChem CID |
166637068
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
33
|
| Complexity |
761
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
S(C1C=CC(=CC=1)OC)(N1CCN(C[C@H]1C(=O)NCC1C=CC(=CC=1)OC)C(=O)CCl)(=O)=O
|
| InChi Key |
SXQZEMXQTRNLRZ-FQEVSTJZSA-N
|
| InChi Code |
InChI=1S/C22H26ClN3O6S/c1-31-17-5-3-16(4-6-17)14-24-22(28)20-15-25(21(27)13-23)11-12-26(20)33(29,30)19-9-7-18(32-2)8-10-19/h3-10,20H,11-15H2,1-2H3,(H,24,28)/t20-/m0/s1
|
| Chemical Name |
(2S)-4-(2-chloroacetyl)-N-[(4-methoxyphenyl)methyl]-1-(4-methoxyphenyl)sulfonylpiperazine-2-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~201.62 mM; with ultrasonication)
|
|---|---|
| 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 | 2.0162 mL | 10.0811 mL | 20.1621 mL | |
| 5 mM | 0.4032 mL | 2.0162 mL | 4.0324 mL | |
| 10 mM | 0.2016 mL | 1.0081 mL | 2.0162 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
