| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
RH01386 targets the endoplasmic reticulum (ER) stress pathway in pancreatic β cells. ER stress is a condition in which the accumulation of unfolded or misfolded proteins in the ER triggers a cellular stress response known as the unfolded protein response (UPR). Chronic ER stress can lead to β cell dysfunction and apoptosis, which are key features of type 2 diabetes. RH01386 prevents ER stress-induced β cell dysfunction and death and inhibits the expression of proapoptotic genes. The compound restores the impaired glucose-stimulated insulin secretory response in ER-stressed cells. By protecting β cells from ER stress-induced damage, RH01386 has potential for type 2 diabetes treatment.
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| ln Vitro |
In βTC6 cells treated with (tunicamycin) Tm, RH01386 (270 nM-70 μM; 72 hours) was demonstrated to raise ATP levels, with an EC50 value of 1.894 μM [1]. In a 72-hour period, RH01386 (270 nM–70 μM) suppresses the βTC6 apoptotic pathway's downstream effector, caspase-3, and impedes the dose-dependently increased cell death caused by Tunisamycin [1].
In vitro, RH01386 protects pancreatic β cells from ER stress-induced dysfunction and apoptosis. The compound inhibits the expression of proapoptotic genes and restores the impaired glucose-stimulated insulin secretory response in ER-stressed cells. These effects are concentration-dependent, with efficacy observed at various concentrations depending on the assay and cell type. RH01386 prevents ER stress-induced β cell dysfunction and death, making it a promising candidate for preserving β cell function. The compound's in vitro activity supports its potential for type 2 diabetes treatment. The compound is supplied as a research chemical with purity >99%. |
| ln Vivo |
In vivo, RH01386 has potential for type 2 diabetes treatment. By protecting pancreatic β cells from ER stress-induced dysfunction and apoptosis, the compound may preserve β cell mass and function, improving glucose homeostasis in diabetic animals. However, detailed in vivo efficacy, pharmacokinetic, and toxicological data for RH01386 require further investigation from primary research publications. The compound's ability to restore glucose-stimulated insulin secretion suggests that it may improve glycemic control in vivo. Further preclinical studies are needed to fully establish its therapeutic potential for type 2 diabetes.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for RH01386 are not standard pharmacological assays, as the compound targets cellular stress pathways rather than a specific enzyme or receptor. However, biochemical assays may be used to study its effects on ER stress markers or apoptosis pathways. For example, the compound's ability to inhibit the expression of proapoptotic genes may be assessed using cell-free transcription assays or by measuring the activity of transcription factors involved in the UPR. Binding studies may be performed to identify the compound's direct molecular targets. These assays help characterize the compound's mechanism of action and identify potential protein targets.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: βTC6 Cell Tested Concentrations: 270 nM-70 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited ER stress-induced βTC6 cell death in a dose-dependent manner. Apoptosis analysis[1] Cell Types: βTC6 Cells Tested Concentrations: 270 nM-70 μM Incubation Duration: 72 hrs (hours) Experimental Results: Protection of βTC6 cells from Tm-induced cell death. In vitro cellular experiments with RH01386 are performed using pancreatic β cell lines such as INS-1, MIN6, or primary rat or human islets. Cells are cultured in appropriate media and treated with ER stress-inducing agents (e.g., thapsigargin, tunicamycin, or palmitate) in the presence or absence of varying concentrations of RH01386. ER stress markers (e.g., CHOP, BiP, XBP-1 splicing) are assessed by RT-qPCR or Western blot analysis. Apoptosis is evaluated by Annexin V/PI staining, caspase activity assays, or TUNEL staining. Glucose-stimulated insulin secretion (GSIS) is measured by ELISA or RIA following glucose stimulation. The compound's ability to restore GSIS in ER-stressed cells is a key endpoint. |
| Animal Protocol |
In vivo animal studies with RH01386 have not been extensively reported. For type 2 diabetes research, standard in vivo models include high-fat diet-fed mice, db/db mice, or streptozotocin (STZ)-induced diabetic models. Mice are treated with RH01386 via oral, intraperitoneal, or subcutaneous administration at various doses and schedules. Efficacy is assessed by measuring blood glucose levels, glucose tolerance tests (GTT), insulin tolerance tests (ITT), and serum insulin levels. Pancreatic β cell mass and function are assessed by immunohistochemistry and islet morphology. ER stress markers in pancreatic tissues may be measured to confirm target engagement. The compound's potential for type 2 diabetes treatment is based on its ability to protect β cells from ER stress-induced damage.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of RH01386 are not extensively characterized. The compound has molecular formula C₁₈H₁₅F₃N₄O₃S and molecular weight 424.40. As a small molecule (molecular weight 424.40) containing fluorine atoms, it is expected to have reasonable oral bioavailability and metabolic stability. The compound's trifluoromethyl group may contribute to favorable pharmacokinetic properties. Storage: follow manufacturer's guidelines. Detailed pharmacokinetic parameters including half-life, clearance, and bioavailability require further investigation from primary research publications.
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| Toxicity/Toxicokinetics |
Toxicological information for RH01386 is not extensively detailed in the available literature. As a research compound with potential therapeutic applications, it should be handled with appropriate safety precautions. Standard safety guidelines for handling potent pharmaceutical compounds apply, including use of personal protective equipment (gloves, safety goggles, lab coat), working in a well-ventilated area, and proper chemical waste disposal. The compound is intended for research use only and is not approved for human therapeutic use. Cytotoxicity studies in cell-based assays help establish the therapeutic window and selectivity index of the compound.
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| References | |
| Additional Infomation |
RH01386 (CAS 301177-36-6) is a small molecule that protects pancreatic β cells from endoplasmic reticulum (ER) stress-induced dysfunction and apoptosis. The compound has molecular formula C₁₈H₁₅F₃N₄O₃S and molecular weight 424.40. RH01386 inhibits proapoptotic gene expression and restores the impaired glucose-stimulated insulin secretory response in ER-stressed cells. The compound has potential for type 2 diabetes treatment. By preventing ER stress-induced β cell dysfunction and death, RH01386 offers a promising approach for preserving β cell function and treating diabetes. Purity is typically >99%.
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| Molecular Formula |
C18H15F3N4O3S
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| Molecular Weight |
424.396912813187
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| Exact Mass |
424.081
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| CAS # |
301177-36-6
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| PubChem CID |
135441816
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
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| Complexity |
790
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(C(F)(F)F)=CC=1[N+](=O)[O-])C1NC(C(C#N)=C(C2CCCCC2)N=1)=O
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| InChi Key |
BVWCKDMNROTYMZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H15F3N4O3S/c19-18(20,21)11-6-7-14(13(8-11)25(27)28)29-17-23-15(10-4-2-1-3-5-10)12(9-22)16(26)24-17/h6-8,10H,1-5H2,(H,23,24,26)
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| Chemical Name |
4-cyclohexyl-2-[2-nitro-4-(trifluoromethyl)phenyl]sulfanyl-6-oxo-1H-pyrimidine-5-carbonitrile
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| Synonyms |
RH01386; RH-01386
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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 : ~100 mg/mL (~235.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.89 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3563 mL | 11.7813 mL | 23.5627 mL | |
| 5 mM | 0.4713 mL | 2.3563 mL | 4.7125 mL | |
| 10 mM | 0.2356 mL | 1.1781 mL | 2.3563 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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