| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
SHIN1 targets human serine hydroxymethyltransferase 1 (SHMT1) and 2 (SHMT2), key enzymes in one-carbon metabolism, with IC50 values of 5 nM and 13 nM, respectively.
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| ln Vitro |
Human SHIN1 SHMT1/2 is inhibited by SHIN1 (RZ-2994) in solution tests, with IC50 values of 5 and 13 nM, respectively. With an IC50 of 10 nM, SHIN1 inhibits SHMT2 and prevents HCT-116 cells from growing. In HCT -116 cells, SHIN1 (RZ-2994) suppresses SHMT1/2. Particularly effective against B cell malignancies is SHIN1 (RZ-2994). By gradually reducing purine levels, SHIN1 stops cell development and causes tertiary loss that is lethal [1].
In vitro, SHIN1 potently inhibits SHMT1 and SHMT2 with IC50s of 5 and 13 nM, respectively. It blocks the growth of HCT-116 cells with an IC50 of 870 nM. It impairs cell growth at concentrations <100 nM. |
| ln Vivo |
In vivo, SHIN1 has shown anti-cancer activity in preclinical models. It disrupts one-carbon metabolism, leading to the depletion of purines and impaired DNA synthesis, which inhibits tumor growth. It is particularly active against B-cell malignancies.
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| Enzyme Assay |
In vitro enzyme assays for SHIN1 measure the inhibition of purified human SHMT1 and SHMT2 enzymatic activity. The enzymes catalyze the conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylene-THF. The reaction is typically coupled to a downstream enzyme (e.g., methylene-THF dehydrogenase) and the formation of NADPH is measured spectrophotometrically. The IC50 is determined from inhibition curves.
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| Cell Assay |
In vitro cellular assays for SHIN1 are performed using cancer cell lines, such as HCT-116 (colon cancer) or various B-cell malignancy cell lines. Cells are treated with the compound for 48-72 hours, and cell proliferation is measured using CellTiter-Glo or MTT assays. The compound's effect on one-carbon metabolism is assessed by measuring nucleotide levels (purines and pyrimidines) by LC-MS/MS.
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| Animal Protocol |
In vivo animal studies for SHIN1 are conducted in mouse xenograft models using cancer cell lines. Tumor-bearing mice are treated with the compound orally or intraperitoneally, and tumor volume is measured. The compound's ability to inhibit tumor growth and its effects on nucleotide pools in the tumor tissue are assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for SHIN1 are not detailed in publicly available sources. As a cell-permeable inhibitor, it is designed for cellular activity. Its PK properties would be characterized in preclinical models for further development. It is expected to have oral bioavailability.
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| Toxicity/Toxicokinetics |
Toxicological data for SHIN1 are not widely published. As a research compound in preclinical development, its safety profile would be assessed in standard toxicology studies. No significant toxicity has been reported in the available literature.
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| References | |
| Additional Infomation |
SHIN1 is a research compound also known as RZ-2994. It is a potent inhibitor of SHMT1 and SHMT2 and is used as a tool to study one-carbon metabolism and its role in cancer cell proliferation. It has shown anti-cancer activity, particularly against B-cell malignancies. It is not an approved drug.
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| Molecular Formula |
C24H24N4O2
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|---|---|
| Molecular Weight |
400.472965240479
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| Exact Mass |
400.189
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| CAS # |
2146095-85-2
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| Related CAS # |
(+)-SHIN1;2443966-90-1;(-)-SHIN1;2444764-09-2
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| PubChem CID |
134335083
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
707
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(=C(C#N)C(C2C=C(CO)C=C(C3C=CC=CC=3)C=2)(C2=C(C)NN=C12)C(C)C)N
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| InChi Key |
VVVOFJZXKJKHTD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24N4O2/c1-14(2)24(20(12-25)22(26)30-23-21(24)15(3)27-28-23)19-10-16(13-29)9-18(11-19)17-7-5-4-6-8-17/h4-11,14,29H,13,26H2,1-3H3,(H,27,28)
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| Chemical Name |
6-amino-4-[3-(hydroxymethyl)-5-phenylphenyl]-3-methyl-4-propan-2-yl-2H-pyrano[2,3-c]pyrazole-5-carbonitrile
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| Synonyms |
RZ-2994RZ2994SHIN 1 SHIN-1 SHIN1
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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 : ~66.67 mg/mL (~166.48 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (3.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4971 mL | 12.4853 mL | 24.9707 mL | |
| 5 mM | 0.4994 mL | 2.4971 mL | 4.9941 mL | |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4971 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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