| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
RBPJ (recombination signal binding protein for immunoglobulin kappa J region). RIN1 disrupts the functional interaction between RBPJ and SHARP, a scaffold protein that forms a transcriptional repressor complex with RBPJ in the absence of Notch signaling, thus inhibiting Notch-mediated transcription.
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| ln Vitro |
RIN1 suppresses the growth of blood cancer cell lines and stimulates skeletal muscle development from C2C12 myoblasts [1]. RIN1 (0.6 μM, equivalent to 3 times IC50) has been shown to cause the production of multinucleated myofibers because it decreases the number of MHC+ cells and increases the number of nuclei per cell [1].
RIN1 inhibits Hes1-Luciferase activity with an IC50 of 0.18 uM and Emax of 82% in AD-293 cells transfected with RBPJ-VP16. It inhibits NOTCH3 ICD with similar potency (IC50 = 0.19 uM, Emax = 88%). RIN1 (0.6 uM, ~3× IC50) induces multinucleated myofiber formation. RIN1 (0.1-10 uM; 96 h) inhibits Notch-dependent tumor cell proliferation in T-ALL and mantle cell lymphoma lines. |
| ln Vivo |
RIN1 inhibits Notch-dependent tumor cell proliferation. It suppresses the growth of blood cancer cell lines and stimulates skeletal muscle development from C2C12 myoblasts, as indicated by increased multinucleated myofiber formation. These effects are mediated through disruption of the RBPJ-SHARP interaction, leading to reduced Notch target gene expression and altered cellular differentiation.
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| Enzyme Assay |
Cell-free binding assays between RBPJ and its interacting proteins (e.g., SHARP) can be performed using recombinant proteins. RIN1 is incubated with His-tagged RBPJ and GST-tagged SHARP in binding buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.1% NP-40) for 1-2 hours at 4degC. Protein complexes are pulled down using glutathione beads, washed, and analyzed by SDS-PAGE and Western blotting with anti-His antibody. IC50 for disruption can be determined by measuring bound protein density.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: AD-293 cells were transfected with RBPJ-VP16myc. Tested Concentrations: 2 μM. Incubation Duration: 17 hrs (hours). Experimental Results: Inhibited Hes1-Luciferase activity with an IC50 of 0.18 µM and Emax of 82%. Inhibited NOTCH3 ICD with similar potency and efcacy (0.19 µM and Emax=88%). Cell Proliferation Assay[1] Cell Types: T-cell acute lymphoblastic leukemia (T-ALL) patients (Jurkat and KOPT-K1) and in the mantle cell lymphoma (MCL) line REC-1. Tested Concentrations: 0.1-10 μM. Incubation Duration: 96 h. Experimental Results: Inhibited NOTCH-dependent tumor cell proliferation. Was active in both the cancer cell anti-proliferation and myoblast diferentiation assays. AD-293 cells are transiently transfected with RBPJ-VP16myc and a Hes1-luciferase reporter construct. Twenty-four hours post-transfection, cells are treated with RIN1 (0.1-10 uM) for 17 hours. Luciferase activity is measured using a luminometer. For cell proliferation assays, T-ALL cells (Jurkat, KOPT-K1) and mantle cell lymphoma REC-1 cells are treated with RIN1 (0.1-10 uM) for 96 hours. Cell viability is assessed by CellTiter-Glo or MTS assay. For myoblast differentiation, C2C12 myoblasts are treated with RIN1 (0.6 uM) for 2-7 days; differentiation is assessed by MHC immunofluorescence staining. |
| Animal Protocol |
No published in vivo animal protocols are available for RIN1. For potential in vivo efficacy studies, RIN1 would be administered to Notch-dependent tumor xenograft mouse models (e.g., T-ALL xenografts) by intraperitoneal injection at doses ranging from 10-50 mg/kg daily for 2-4 weeks. Tumor volumes would be measured with calipers. Tumor tissue would be collected for analysis of Notch target genes (Hes1, Hey1) by qRT-PCR. No such studies have been reported.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are reported for RIN1. The molecular formula is C17H14FN3O2 with molecular weight 311.31 g/mol, LogP 2.4. In vitro solubility: DMSO 62 mg/mL (199.15 mM). For oral administration, a homogeneous suspension can be prepared using CMC-Na (5 mg/mL). For injection, a clear solution can be formulated using 5% DMSO + 40% PEG300 + 5% Tween 80 + 50% ddH2O (0.300 mg/mL). RIN1 is expected to be metabolically stable, but this has not been confirmed.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for RIN1. In cell-based assays at concentrations up to 10 uM, no overt cytotoxicity was observed in cancer cell lines. However, comprehensive toxicological assessments (hERG, Ames, repeated-dose toxicity) have not been performed. RIN1 has not entered clinical trials, and its safety in animals and humans is unknown.
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| References | |
| Additional Infomation |
Other information: RIN1 (RBPJ Inhibitor-1) is the first described small-molecule RBPJ inhibitor. CAS#: 2682114-39-0. Purity ≥98%. It is a research compound, not FDA-approved. RIN1 is a valuable tool for studying Notch signaling biology and the therapeutic potential of targeting RBPJ in Notch-dependent cancers, including T-cell acute lymphoblastic leukemia (T-ALL). For research use only.
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| Molecular Formula |
C17H14FN3O2
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| Molecular Weight |
311.310367107391
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| Exact Mass |
311.107
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| CAS # |
2682114-39-0
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| PubChem CID |
146019721
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| Appearance |
Light yellow to light brown solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
423
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(N)(=O)C1=CC=C(C2N(C)N=CC=2)C=C1OC1=CC=CC=C1F
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| InChi Key |
MFSSHRCJKRDIOL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H14FN3O2/c1-21-14(8-9-20-21)11-6-7-12(17(19)22)16(10-11)23-15-5-3-2-4-13(15)18/h2-10H,1H3,(H2,19,22)
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| Chemical Name |
2-(2-fluorophenoxy)-4-(2-methylpyrazol-3-yl)benzamide
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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: 250 mg/mL (803.06 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.68 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 20.8 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: ≥ 2.08 mg/mL (6.68 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 20.8 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: ≥ 2.08 mg/mL (6.68 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 | 3.2122 mL | 16.0612 mL | 32.1223 mL | |
| 5 mM | 0.6424 mL | 3.2122 mL | 6.4245 mL | |
| 10 mM | 0.3212 mL | 1.6061 mL | 3.2122 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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