Kevetrin hydrochloride (also known as thioureidobutyronitrile; 4-Isothioureidobutyronitrile hydrochloride; thioureidobutyronitrile hydrochloride; thioureido butyronitrile hydrochloride), is a water-soluble, small molecule activator of the tumor suppressor protein p53. Potentially, it has anti-cancer properties. After being injected, thioureidobutyronitrile activates p53, which in turn triggers the expression of p21 and PUMA (p53 up-regulated modulator of apoptosis), inhibiting the growth of cancer cells and causing tumor cell apoptosis. In drug-resistant cancers with mutated p53, thioureidobutyronitrile might be useful. In cancer cells, the p53 tumor suppressor, a transcription factor controlling the expression of numerous stress response genes and mediating various anti-proliferative processes, is frequently mutated. a little chemical that has the potential to be anti-cancer and activates the p53 tumor suppressor protein.
Physicochemical Properties
| Molecular Formula | C5H10CLN3S | |
| Molecular Weight | 179.67 | |
| Exact Mass | 179.028 | |
| Elemental Analysis | C, 33.43; H, 5.61; Cl, 19.73; N, 23.39; S, 17.84 | |
| CAS # | 66592-89-0 | |
| Related CAS # | Kevetrin hydrochloride-13C2,15N3;2300178-72-5 | |
| PubChem CID | 49778916 | |
| Appearance | white solid powder | |
| Melting Point | 125-127 ºC | |
| LogP | 2.518 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 4 | |
| Heavy Atom Count | 10 | |
| Complexity | 134 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | Cl[H].S(/C(=N\[H])/N([H])[H])C([H])([H])C([H])([H])C([H])([H])C#N |
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| InChi Key | NCXJZJFDQMKRKM-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C5H9N3S.ClH/c6-3-1-2-4-9-5(7)8;/h1-2,4H2,(H3,7,8);1H | |
| Chemical Name | 3-cyanopropyl carbamimidothioate;hydrochloride | |
| Synonyms |
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| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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 | The proliferation of KASUMI-1 cells was considerably suppressed, dose-wise, by kevetrin hydrochloride (85, 170, 340 μM; 6 h), but not that of MOLM-13 [1]. Kevetrin hydrochloride (340 μM; 6) induces metallothionein (MT) expression in acute myeloid leukemia (AML) cells and downregulates p53 activity. Kevetrin hydrochloride (340 μM; 24 hours) induces KASUMI-1 cell line cells without causing changes to the cell cycle. Kevetrin hydrochloride is the forkhead box K2 regulator of WNT/β-catenin signaling Regulator-related gene signal transducer and regulatory activator 5A (STAT5A). P53 is increased by kevetrin hydrochloride (100, 200, and 400 μM; 48 h)[1]. |
| ln Vivo | In tumor xenograft models, kevetrin hydrochloride (150–200 mg/kg; i.p.; 20 days) suppresses tumor development and prolongs focus, and it promotes about 40% cell death in OV-90 or OVCAR-3 xenograft tumors. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: MOLM-13 and KASUMI-1 cells Tested Concentrations: 85, 170 and 340 µM Incubation Duration: 6 h, 6 h + mRNA and protein levels, and induce A2780 cells to produce p21 protein[1]. 66 h Wash-out (wo,×1), 6 h + 66 h wo (×2), 6 h + 66 h wo (×3) Experimental Results: Only inhibited the cell viability of KASUMI-1 cells, reducing the cell viability dose and time dependent manner. Apoptosis analysis[1] Cell Types: MOLM-13, KASUMI-1, TP53-wt OCI-AML3 and TP53 mutant NOMO-1 Cell Tested Concentrations: 85, 170 and 340 µM Incubation Duration: 24, 48 and 72 hrs (hours) Experimental Results: Induces apoptosis of KASUMI-1 cells at 340 μM concentration for 24 hrs (hours) and inhibits MOLM-13 at 340 μM concentration for 48 hrs (hours). Cell cycle analysis[1] Cell Types: MOLM-13, KASUMI-1, TP53-wt OCI-AML3 and TP53 mutant NOMO-1 Cell Tested Concentrations: 340 µM Incubation Duration: 24 and 48 hrs (hours) Experimental Results: Cell cycle arrest OCI-AML3 and NOMO-1 cells are in the G0/G1 phase, and does not change the cell cycle of MOLM-13 and KASUMI-1 cells. |
| Animal Protocol |
Animal/Disease Models: A2780 nude mouse xenograft tumor model [2] Doses: 200 mg/kg Route of Administration: intraperitoneal (ip) injection; time [2]. 3 times a week for 20 days Experimental Results: Inhibition of tumor growth and suppression of tumor volume. Animal/Disease Models: Mouse SKOV-3 xenograft ascites model [2] Doses: 150 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Prolonged mouse survival time, maintaining 100% survival rate for more than 35 days. |
| References |
[1]. Kevetrin induces apoptosis in TP53 wildtype and mutant acute myeloid leukemia cells. Oncol Rep. 2020 Oct;44(4):1561-1573. [2]. Kevetrin induces p53-dependent and independent cell cycle arrest and apoptosis in ovarian cancer cell lines representing heterogeneous histologies. |
| Additional Infomation | See also: 4-Isothioureidobutyronitrile (annotation moved to). |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (13.91 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 25.0 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: ≥ 2.5 mg/mL (13.91 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 25.0 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: ≥ 2.5 mg/mL (13.91 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (556.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.5658 mL | 27.8288 mL | 55.6576 mL | |
| 5 mM | 1.1132 mL | 5.5658 mL | 11.1315 mL | |
| 10 mM | 0.5566 mL | 2.7829 mL | 5.5658 mL |