| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Serine hydroxymethyltransferase (SHMT)[1]
SHMT (serine hydroxymethyltransferase), both the cytosolic (SHMT1) and mitochondrial (SHMT2) isoforms. SHMT catalyzes the reversible conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-CH2-THF), a crucial step in one-carbon metabolism that provides building blocks for DNA and RNA synthesis. |
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| ln Vitro |
(Met(O)35)-Amyloid β-Protein(1-42) yields
(+)SHIN2 binds strongly to the SHMT active site, likely by stabilizing the active site loop, thereby inhibiting enzymatic activity. It exhibits potent growth inhibition in cancer cells reliant on one-carbon metabolism. In T-ALL cell lines, it synergizes with Methotrexate, enhancing anti-leukemic effects. Its target engagement can be traced with 13C-serine tracing. |
| ln Vivo |
In mice with primary T-ALL, (+)SHIN2 (200 mg/kg; ip; single dosage) exhibits therapeutic activity[1].
In NOTCH1-driven primary mouse acute T-lymphoblastic leukemia (T-ALL) models, (+)SHIN2 significantly increases survival. When combined with methotrexate, it shows a synergistic effect, achieving greater tumor regression and prolonged survival compared to either agent alone. This demonstrates that SHMT inhibition is a valid therapeutic strategy in vivo. |
| Enzyme Assay |
SHMT enzyme activity assay is performed in cell-free systems using recombinant SHMT1 or SHMT2. Enzyme is incubated with varying concentrations of (+)SHIN2, serine, and radiolabeled THF (e.g., [14C]-THF) in reaction buffer. After incubation at 37degC, the reaction is quenched, and the product (radiolabeled 5,10-CH2-THF) is separated by HPLC or charcoal adsorption and quantified by liquid scintillation counting to determine IC50.
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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. Synergy is calculated using the Chou-Talalay method (Combination Index). One-carbon metabolism is assessed by measuring 13C-serine incorporation into nucleotides via LC-MS.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (10-14 weeks old) with mouse primary T- ALL[1]
Doses: 200 mg/kg Route of Administration: intraperitoneal (ip)injection; prepared with 30 mM U-13C-Serine (0.1 μL/min/g; infusion by catheter implanted on the right jugular vein); tested at 8 hr after treatment Experimental Results: diminished thymus weight and cellularity, which normalized after treatment discontinuation. demonstrated generally well tolerated activity with modest hematological toxicity. In vivo xenograft models: NOTCH1-driven T-ALL cells are transplanted via tail vein injection into immunodeficient NSG mice. After engraftment (detected by human CD45+ cells in peripheral blood), mice are treated daily with (+)SHIN2 (oral or IP injection, typical doses 25-100 mg/kg) or methotrexate. Survival is monitored using Kaplan-Meier analysis. Bone marrow and spleen are harvested for flow cytometry analysis of leukemia burden. |
| ADME/Pharmacokinetics |
Preclinical pharmacokinetic data indicates that (+)SHIN2 has sufficient oral bioavailability to achieve efficacious concentrations in vivo. Key parameters include moderate plasma clearance and a half-life suitable for once-daily dosing. (+)SHIN2 is permeable and distributes into tissues, including bone marrow, the primary site of leukemia. It is stable in plasma.
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| Toxicity/Toxicokinetics |
In animal studies, (+)SHIN2 is generally well-tolerated at therapeutic doses. Common side effects associated with anti-folate therapies (e.g., gastrointestinal disturbances) were minimal. No significant weight loss or hepatotoxicity was observed in treated mice. The drug appears to have a favorable safety margin, especially when combined with methotrexate.
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| References | |
| Additional Infomation |
(+)SHIN2 is a research-grade chemical tool compound developed for studying SHMT biology in cancer. It was discovered by the laboratory of Dr. Nada Kalaany (Boston Children's Hospital/Harvard). It is not yet in clinical trials for human cancer therapy, but it serves as a lead compound for the development of new drugs targeting one-carbon metabolism. It is also a click chemistry reagent containing alkyne groups.
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| CAS # |
3056942-19-6
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| Related CAS # |
(Rac)-SHIN2;2204289-53-0;(-)SHIN2
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| Appearance |
White to light 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.) |
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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