| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
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| Targets |
FHT-1015 targets SMARCA4 (BRG1) and SMARCA2 (BRM), the catalytic ATPase subunits of the BAF (BRG/Brahma-associated factors) chromatin remodeling complex. The BAF complex plays a critical role in regulating gene expression by altering chromatin structure. SMARCA4 and SMARCA2 are frequently mutated or dysregulated in cancer, contributing to tumorigenesis and drug resistance. By allosterically inhibiting SMARCA4/SMARCA2 ATPase activity, FHT-1015 disrupts BAF complex function, leading to altered chromatin remodeling and gene expression. This results in decreased proliferation and survival of cancer cells. The compound's potent and selective inhibition of SMARCA4/SMARCA2 makes it a valuable tool for studying chromatin biology and for developing novel anticancer therapeutics.
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| ln Vitro |
In vitro, FHT-1015 demonstrates potent inhibition of SMARCA4/SMARCA2 ATPase with IC50 values of ≤10 nM. The compound is a selective allosteric inhibitor, binding to a site distinct from the ATP-binding pocket. In cell-based assays, FHT-1015 decreases cell proliferation and induces apoptosis in cancer cell lines dependent on SMARCA4/SMARCA2 function. The compound modulates gene expression programs regulated by the BAF complex, including those involved in cell cycle control, differentiation, and immune regulation. FHT-1015 exhibits potential anticancer activity and is being studied for cancer and inflammatory diseases. Its potent and selective inhibition makes it a valuable tool for studying chromatin remodeling and for developing novel anticancer therapeutics.
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| ln Vivo |
In vivo, FHT-1015 has demonstrated efficacy in preclinical models of cancer and inflammation. The compound decreases PD1+TIM3+ cells and cytokine expression in vivo, suggesting immunomodulatory effects. It exhibits potential anticancer activity and is being studied for cancer and inflammatory diseases. FHT-1015 is typically administered via oral or intraperitoneal routes in preclinical studies. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo. The compound represents a promising approach for targeting chromatin remodeling in cancer and inflammatory diseases.
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| Enzyme Assay |
The in vitro SMARCA4/SMARCA2 ATPase inhibition assay for FHT-1015 typically uses purified recombinant SMARCA4 or SMARCA2 protein and a DNA template. The assay is performed in 96-well plates with ATP and varying concentrations of the test compound (typically 0.1 nM to 10 µM). The ATPase activity is measured by quantifying the release of inorganic phosphate using a colorimetric or fluorometric detection method (e.g., malachite green assay). IC50 values are calculated from dose-response curves using nonlinear regression. For selectivity profiling, the compound is tested against a panel of ATPases and unrelated targets. For cell-based assays, the effects of the compound on BAF complex function are assessed by measuring chromatin remodeling activity and gene expression changes. Positive controls (e.g., known SMARCA4 inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines (e.g., SMARCA4-deficient or SMARCA4-dependent cells) are treated with FHT-1015 at concentrations ranging from 0.1 nM to 10 µM for 24-72 hours. Cell viability is assessed using CellTiter-Glo or MTT assays. Gene expression changes are assessed by RNA-seq or qRT-PCR. Chromatin remodeling is assessed by ATAC-seq or ChIP-seq for BRG1/BRM occupancy. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. Immune modulation is assessed by measuring PD1+TIM3+ cell populations and cytokine expression by flow cytometry and ELISA. All experiments include appropriate controls and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are subcutaneously inoculated with cancer cells (e.g., SMARCA4-deficient or SMARCA4-dependent tumors). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). FHT-1015 is administered orally or intraperitoneally at doses ranging from 1 to 100 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for immunohistochemistry (Ki67, CD3, CD8) and Western blot analysis. Immune cell populations and cytokine expression are assessed in blood and tumor tissues. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of FHT-1015 have been partially characterized. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 1-3 hours. Plasma half-life is estimated to be 4-8 hours. The compound distributes into tissues including tumor, liver, and spleen. Plasma protein binding is moderate to high. Metabolism is primarily hepatic, with CYP450-mediated oxidation and conjugation as major pathways. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. Further PK studies are needed for comprehensive characterization. Detailed PK data are limited in publicly available sources.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of FHT-1015 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
CID 139371523 is an organic molecular entity.
FHT-1015 is a potent, selective, allosteric inhibitor of SMARCA4/SMARCA2 ATPase (BRG1/BRM) with IC50 ≤10 nM. It exhibits anticancer activity and decreases PD1+TIM3+ cells and cytokine expression in vivo. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent for laboratory use only. Its potent and selective inhibition of SMARCA4/SMARCA2 makes it a valuable tool for studying chromatin remodeling, cancer biology, and for developing novel anticancer and anti-inflammatory therapeutics. |
| Molecular Formula |
C25H25N5O4S3
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|---|---|
| Molecular Weight |
555.69
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| Exact Mass |
555.106
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| CAS # |
2368903-18-6
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| PubChem CID |
139371523
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
37
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| Complexity |
880
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1(S(C)(=O)=O)C=CC(C(N[C@H](C(NC2=NC(C3=CC=CC(C4C=CN=CC=4)=C3)=CS2)=O)CCSC)=O)=C1
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| InChi Key |
FAYSHZVDWADZMD-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C25H25N5O4S3/c1-35-13-9-21(27-23(31)20-8-12-30(15-20)37(2,33)34)24(32)29-25-28-22(16-36-25)19-5-3-4-18(14-19)17-6-10-26-11-7-17/h3-8,10-12,14-16,21H,9,13H2,1-2H3,(H,27,31)(H,28,29,32)/t21-/m0/s1
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| Chemical Name |
N-[(2S)-4-methylsulfanyl-1-oxo-1-[[4-(3-pyridin-4-ylphenyl)-1,3-thiazol-2-yl]amino]butan-2-yl]-1-methylsulfonylpyrrole-3-carboxamide
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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 (~179.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.50 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7996 mL | 8.9978 mL | 17.9956 mL | |
| 5 mM | 0.3599 mL | 1.7996 mL | 3.5991 mL | |
| 10 mM | 0.1800 mL | 0.8998 mL | 1.7996 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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