| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
SHMT (serine hydroxymethyltransferase), specifically targeting the one-carbon metabolic pathway essential for nucleotide synthesis. While the active (+)SHIN2 enantiomer binds to the SHMT active site, the (-)-enantiomer has significantly lower binding affinity and is expected to show minimal inhibition of the enzyme's catalytic activity.
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| ln Vitro |
In cell-free enzymatic assays using recombinant SHMT1 or SHMT2, (-)SHIN2 shows substantially weaker inhibition compared to (+)SHIN2. Its IC50 for SHMT inhibition is orders of magnitude higher, making it an appropriate negative control to validate that observed biological effects are dependent on SHMT inhibition and not due to off-target activities.
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| ln Vivo |
In xenograft models of T-ALL, (-)SHIN2 is not expected to increase survival or reduce leukemia burden when administered alone. It serves as a critical control in combination studies with methotrexate to demonstrate that enhanced efficacy observed with (+)SHIN2 is stereospecific and mediated specifically through SHMT inhibition rather than nonspecific chemical interactions.
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| Enzyme Assay |
SHMT enzyme activity assay is performed in cell-free systems. Recombinant SHMT1 or SHMT2 is incubated with varying concentrations of (-)SHIN2 (typically 0.1 nM to 100 uM), serine, and radiolabeled THF in reaction buffer. After incubation at 37degC, the reaction product is quantified. The IC50 of (-)SHIN2 is compared to the active (+)SHIN2 enantiomer. Greater than 100-fold difference in potency is expected.
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| Cell Assay |
T-ALL cell lines (e.g., Jurkat or patient-derived NOTCH1-driven cells) are seeded in 96-well plates and treated with (-)SHIN2 (0.1 nM - 10 uM) alone or in combination with methotrexate for 72 hours. Cell viability is assessed by MTT or CellTiter-Glo. The (-)-enantiomer should show minimal effect on cell viability compared to the active enantiomer, validating target specificity.
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| Animal Protocol |
In NOTCH1-driven T-ALL xenograft models, NSG mice transplanted with leukemia cells are treated daily with (-)SHIN2 (oral or IP, matching active enantiomer doses, e.g., 25-100 mg/kg) or vehicle control. Survival is monitored. The (-)-enantiomer treatment group is expected to show no significant survival benefit compared to vehicle, confirming that anti-leukemic activity of (+)SHIN2 is target-mediated.
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| ADME/Pharmacokinetics |
As the inactive enantiomer, (-)SHIN2 is expected to have similar physicochemical properties and absorption characteristics as the active enantiomer, but with negligible target engagement. Its PK profile (e.g., oral bioavailability, half-life, clearance) should be comparable to the active compound, making it an ideal control for PK/PD studies to separate target-specific from non-specific effects.
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| Toxicity/Toxicokinetics |
Toxicology studies are not typically performed for the inactive enantiomer alone. At the doses used in control experiments, (-)SHIN2 is not expected to cause significant toxicity as it does not engage the SHMT target. In animal studies comparing active and inactive enantiomers at matched doses, the (-) isomer should not induce weight loss or hematologic abnormalities.
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| References | |
| Additional Infomation |
(-)SHIN2 is a research-grade chemical used exclusively as an experimental control in studies of SHMT biology and one-carbon metabolism in cancer. The discovery that SHMT inhibition is effective against T-ALL and synergizes with methotrexate was a significant advance. (-)SHIN2 is not a clinical candidate and has no FDA approval. It is a critical reagent for validating mechanism-of-action studies in drug discovery.
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| Molecular Formula |
C23H26N4O3
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|---|---|
| Molecular Weight |
406.48
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| Related CAS # |
(Rac)-SHIN2;2204289-53-0;(+)SHIN2
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| Appearance |
White to yellow 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.4601 mL | 12.3007 mL | 24.6015 mL | |
| 5 mM | 0.4920 mL | 2.4601 mL | 4.9203 mL | |
| 10 mM | 0.2460 mL | 1.2301 mL | 2.4601 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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