| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
SHMT-IN-2 targets the serine hydroxymethyltransferases SHMT1 and SHMT2, which are key enzymes in the folate-mediated one-carbon metabolic pathway. These enzymes catalyze the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate, a crucial step for nucleotide synthesis. By inhibiting SHMT1/2, the compound disrupts one-carbon metabolism, leading to a depletion of nucleotides and the inhibition of cancer cell proliferation.
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| ln Vitro |
SHMT-IN-2 (compound 2) has the ability to suppress cell growth; the cellular IC50 values of SHMT1 and SHMT2 are 2800 nM and 36 nM, respectively [1]. With a median IC50 of 4 μM (IC50 values for CCRF-CEM and HT were 1.72 μM and 1.73 μM, respectively), SHMT-IN-2 (30 μM) demonstrated growth sensitivity against almost 300 human cancer cell lines. B-cell lymphoid tumor-derived cell lines are enriched in the more sensitive half of the cells [1].
In vitro, SHMT-IN-2 is a potent inhibitor of human SHMT1 and SHMT2 with IC50 values of 13 nM and 66 nM, respectively. It can block the growth of many human cancer cells and shows particular sensitivity in B-cell lymphomas. Its activity has been demonstrated in various cancer cell lines. |
| ln Vivo |
In vivo, SHMT-IN-2 has shown anticancer activity in preclinical models. It has been used to effectively inhibit SHMT2 catalytic activity, leading to developmental arrest at the pronuclear stage in embryos. Specific efficacy data in cancer models are not detailed in the available sources.
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| Enzyme Assay |
A cell-free assay for SHMT-IN-2 involves measuring its inhibition of SHMT1 and SHMT2 enzymatic activity. Recombinant SHMT1 or SHMT2 is incubated with serine and tetrahydrofolate in the presence of varying concentrations of the compound. The production of glycine and 5,10-methylenetetrahydrofolate is measured, and the IC50 is calculated. For SHMT-IN-2, the IC50 values are 13 nM for SHMT1 and 66 nM for SHMT2.
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| Cell Assay |
Cellular assays for SHMT-IN-2 typically involve assessing its effects on cancer cell proliferation and one-carbon metabolism. Cells are treated with the compound, and cell viability is measured. The effects on nucleotide levels and the methylation status of DNA and histones can also be assessed to confirm the compound's mechanism of action.
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| Animal Protocol |
In vivo animal experiments for SHMT-IN-2 are not described in the available sources. As a compound with in vitro anticancer activity, it could be evaluated in tumor xenograft models. However, no specific protocols or data are provided.
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| ADME/Pharmacokinetics |
SHMT-IN-2 has a molecular formula of C22H24F3N5O and a molecular weight of 431.45 g/mol. Specific pharmacokinetic parameters are not provided in the available sources. As a research compound, it is intended for preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicity data for SHMT-IN-2 are not provided in the available sources. As a research compound, it is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be observed.
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| References | |
| Additional Infomation |
SHMT-IN-2 (CAS: 2102681-49-0) is a potent and stereospecific inhibitor of human SHMT1 and SHMT2. It is also known as SHIN2. The compound has IC50 values of 13 nM for SHMT1 and 66 nM for SHMT2 and has anticancer activity. It is used in research to study one-carbon metabolism and its role in cancer.
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| Molecular Formula |
C22H24F3N5O
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|---|---|
| Molecular Weight |
431.4541
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| Exact Mass |
431.193
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| CAS # |
2102681-49-0
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| Related CAS # |
2102681-49-0; 2204289-54-1;
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| PubChem CID |
134335070
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| Appearance |
White to off-white solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
769
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1=C([H])C(=C([H])C(=C1[H])C1(C(C#N)=C(N([H])[H])OC2C1=C(C([H])([H])[H])N([H])N=2)C([H])(C([H])([H])[H])C([H])([H])[H])N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H])(F)F
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| InChi Key |
NOKJZHRLDAOFCV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24F3N5O/c1-12(2)21(17(11-26)19(27)31-20-18(21)13(3)28-29-20)14-8-15(22(23,24)25)10-16(9-14)30-6-4-5-7-30/h8-10,12H,4-7,27H2,1-3H3,(H,28,29)
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| Chemical Name |
6-Amino-4-isopropyl-3-methyl-4-(3-(pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
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| Synonyms |
SHMT-IN-2Serine hydroxymethyltranferase inhibitor 2 SHIN-2 SHIN2 SHIN 2
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~100 mg/mL (~231.78 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3178 mL | 11.5888 mL | 23.1777 mL | |
| 5 mM | 0.4636 mL | 2.3178 mL | 4.6355 mL | |
| 10 mM | 0.2318 mL | 1.1589 mL | 2.3178 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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