SHIN1 (RZ-2994; RZ2994; SHIN 1) is a potent inhibitor of human serine hydroxymethyltransferase 1/2 (SHMT1/2) with IC50s of 5 and 13 nM, respectively.
Physicochemical Properties
| Molecular Formula | C24H24N4O2 |
| Molecular Weight | 400.472965240479 |
| Exact Mass | 400.189 |
| CAS # | 2146095-85-2 |
| Related CAS # | (+)-SHIN1;2443966-90-1;(-)-SHIN1;2444764-09-2 |
| PubChem CID | 134335083 |
| Appearance | White to off-white solid powder |
| LogP | 4.4 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 30 |
| Complexity | 707 |
| Defined Atom Stereocenter Count | 0 |
| 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 |
| InChi Key | VVVOFJZXKJKHTD-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 6-amino-4-[3-(hydroxymethyl)-5-phenylphenyl]-3-methyl-4-propan-2-yl-2H-pyrano[2,3-c]pyrazole-5-carbonitrile |
| Synonyms | RZ-2994RZ2994SHIN 1 SHIN-1 SHIN1 |
| 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) |
Biological Activity
| 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]. |
| References |
[1]. Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11404-11409. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~66.67 mg/mL (~166.48 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |