| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
0.0698 nM (DHX9)[1]
DHX9 (ATP-dependent RNA helicase A), a key regulator of RNA metabolism, genome stability, and DNA damage repair. The compound selectively inhibits DHX9 helicase activity over other helicases such as DDX36, BRM, and BRG1. |
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| ln Vitro |
In enzymatic assays, DHX9-IN-2 exhibits potent inhibitory activity against DHX9 helicase with an IC50 of 8 nM. It demonstrates high selectivity, effectively blocking the unwinding activity of DHX9 without significant off-target effects on related helicases, disrupting DNA-RNA hybrid resolution and influencing gene expression and replication stress responses.
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| ln Vivo |
In vivo, DHX9-IN-2 induces strong and sustained tumor growth inhibition or regression in MSI-H/dMMR colorectal cancer (CRC) xenograft models. Its oral bioavailability allows for effective dosing, leading to significant anti-tumor efficacy through the modulation of DHX9-mediated pathways in oncology research settings.
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| Enzyme Assay |
A non-cellular helicase assay is performed using recombinant DHX9 protein and a DNA-RNA substrate. The test compound is pre-incubated with the enzyme at varying concentrations, and the reaction is initiated by adding ATP. After 30-60 minutes at 37degC, the reaction is stopped, and the unwound product is detected using a fluorescence-based or gel-based system to calculate the IC50.
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| Cell Assay |
Cell-based proliferation assays are conducted using CRC cell lines such as HCT116 or SW480. Cells are seeded in 96-well plates and treated with a concentration range of DHX9-IN-2 (0.1-100 uM) for 48-72 hours. Cell viability is measured using MTT or CellTiter-Glo assays to determine the half-maximal inhibitory concentration (IC50) for cell growth inhibition.
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| Animal Protocol |
MSI-H/dMMR colorectal cancer xenograft models are established in immunodeficient mice. Once tumors reach a suitable size, DHX9-IN-2 is administered orally (p.o.) at doses ranging from 1-50 mg/kg daily for 14-21 days. Tumor volumes are measured with calipers every 2-3 days, and body weight is monitored. At study endpoint, tumors are excised and weighed to assess growth inhibition or regression.
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| ADME/Pharmacokinetics |
DHX9-IN-2 is orally bioavailable in preclinical species, with good absorption and systemic exposure following oral administration. It has moderate plasma clearance and a reasonable half-life that supports once-daily dosing in xenograft models. It is soluble in DMSO (84 mg/mL) and can be formulated for in vivo studies using standard vehicles like PEG300 and Tween-80.
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| Toxicity/Toxicokinetics |
Standard toxicology assessments for DHX9-IN-2 are not extensively published. As a research compound, it is intended for laboratory use only and not for human therapeutic applications. Preliminary in vitro cytotoxicity studies suggest a favorable safety window in normal cells, but comprehensive toxicological profiling is required for clinical development.
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| References | |
| Additional Infomation |
The compound is also known as ATX968 and is highly selective for DHX9 over other helicases (IC50=8 nM). It has been cited in high-impact journals such as Nature Medicine for its top-tier quality. It remains a preclinical research tool and has not yet entered human clinical trials or received regulatory approval for any therapeutic indication.
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| Exact Mass |
421.032
|
|---|---|
| CAS # |
2973395-71-8
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| PubChem CID |
169144997
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
628
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(N=CC=C1)C2=CSC(=C2)C(=O)NC3=CC(=CC(=C3)Cl)NS(=O)(=O)C
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| InChi Key |
VDGNPEFFHQRGOP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16ClN3O3S2/c1-11-4-3-5-20-17(11)12-6-16(26-10-12)18(23)21-14-7-13(19)8-15(9-14)22-27(2,24)25/h3-10,22H,1-2H3,(H,21,23)
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| Chemical Name |
N-[3-chloro-5-(methanesulfonamido)phenyl]-4-(3-methyl-2-pyridinyl)thiophene-2-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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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