| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
| Targets |
CHF-6001 targets the phosphodiesterase 4 (PDE4) enzyme family. It is a potent and selective inhibitor of PDE4, with an IC50 of 0.026 ± 0.006 nM. The compound inhibits all PDE4 isoforms (A, B, C, and D) with equal potency. It has an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (>40), which is characteristic of a PDE4 inhibitor with a favorable therapeutic profile. CHF-6001 also demonstrates >20,000-fold selectivity versus a panel of other PDEs.
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|---|---|
| ln Vitro |
In vitro, CHF-6001 demonstrates potent anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines. It effectively inhibits the release of tumor necrosis factor-α (TNF-α) from human peripheral blood mononuclear cells (PBMCs), human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383) with subnanomolar IC50 values. It is significantly more potent than other PDE4 inhibitors, being 7-fold more potent than roflumilast and 923-fold more potent than cilomilast.
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| ln Vivo |
In vivo, CHF-6001 has demonstrated robust anti-inflammatory activity in animal models of pulmonary inflammation. As an inhaled compound, it is designed to maximize therapeutic activity in the lung compartment while minimizing systemic exposure and associated side effects. The compound has been studied in clinical trials for the treatment of respiratory conditions such as asthma and COPD. Its efficacy and safety profile in humans have been evaluated in these studies.
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| Enzyme Assay |
PDE4 enzyme inhibition assays are performed using purified PDE4 enzymes or cell lysates containing the enzyme. Enzyme activity is measured by quantifying the hydrolysis of a fluorescent or radiolabeled cAMP substrate. CHF-6001 is tested at various concentrations, and IC50 values are calculated from dose-response curves. Selectivity is assessed by testing the compound against a panel of other PDE isoforms to confirm its specificity for PDE4.
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| Cell Assay |
In vitro cellular assays are performed using immune cells such as human PBMCs, THP-1 macrophages, or RAW264.7 macrophages. Cells are cultured in appropriate media at 37°C in a 5% CO₂ incubator. CHF-6001, dissolved in DMSO, is added to the culture medium at various concentrations, typically in the subnanomolar to nanomolar range. Cells are stimulated with lipopolysaccharide (LPS) or other inflammatory stimuli to induce cytokine production. The release of TNF-α and other pro-inflammatory cytokines is measured by ELISA. IC50 values for cytokine inhibition are determined from dose-response curves.
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| Animal Protocol |
In vivo efficacy is evaluated in animal models of pulmonary inflammation, such as the LPS-induced acute lung injury model or the ovalbumin-induced asthma model in rodents. CHF-6001 is administered via inhalation (e.g., by nebulization or intratracheal instillation) to deliver the compound directly to the lungs. Endpoints include the measurement of inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF), assessment of airway hyperresponsiveness, and histopathological analysis of lung tissues. Pharmacokinetic studies are conducted to measure the compound's concentration in the lung and plasma.
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| ADME/Pharmacokinetics |
CHF-6001 has a molecular weight of 687.5 g/mol and a molecular formula of C30H30Cl2F2N2O8S. Its CAS number is 1239278-59-1. The compound is a solid powder that is soluble in DMSO but not in water. For short-term storage (days to weeks), it should be kept dry, dark, and at 0-4°C. For long-term storage (months to years), it should be stored at -20°C. As an inhaled drug, its pharmacokinetic profile is characterized by high local concentrations in the lung and low systemic exposure.
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| Toxicity/Toxicokinetics |
Specific toxicity data for CHF-6001 are documented in preclinical and clinical studies. As a PDE4 inhibitor, its most common side effects are gastrointestinal, including nausea, vomiting, and diarrhea, which are a result of the compound's mechanism of action and are typically dose-limiting for oral PDE4 inhibitors. However, because CHF-6001 is administered via inhalation, systemic exposure is minimized, which is expected to reduce these gastrointestinal side effects while maintaining efficacy in the lung. Other potential adverse effects may include headache and nasopharyngitis. The compound should be used with caution in patients with a history of gastrointestinal disorders.
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| References | |
| Additional Infomation |
CHF6001 has been used in trials investigating the treatment of asthma and chronic obstructive pulmonary disease.
CHF-6001 (Tanimilast) is a novel, potent, and selective PDE4 inhibitor developed for the inhaled treatment of respiratory inflammatory diseases. It has demonstrated subnanomolar potency in enzymatic assays and robust anti-inflammatory activity in cellular and in vivo models. As a second-generation inhaled PDE4 inhibitor, it was rationally designed to overcome the systemic tolerability limitations of oral PDE4 inhibitors like roflumilast. The compound has the potential to be an effective topical treatment for conditions associated with pulmonary inflammation, including asthma and COPD. It is commercially available as a research compound. |
| Molecular Formula |
C30H30CL2F2N2O8S
|
|---|---|
| Molecular Weight |
687.5328
|
| Exact Mass |
686.106
|
| CAS # |
1239278-59-1
|
| Related CAS # |
(R)-Tanimilast
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| PubChem CID |
70662473
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
811.5±75.0 °C at 760 mmHg
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| Flash Point |
444.6±37.1 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.631
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| LogP |
4.43
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
45
|
| Complexity |
1070
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CS(=O)(=O)NC1=C(C=C(C=C1)C(=O)O[C@@H](CC2=C(C=[N+](C=C2Cl)[O-])Cl)C3=CC(=C(C=C3)OC(F)F)OCC4CC4)OCC5CC5
|
| InChi Key |
VCFBPAOSTLMYIV-SANMLTNESA-N
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| InChi Code |
InChI=1S/C30H30Cl2F2N2O8S/c1-45(39,40)35-24-8-6-20(11-27(24)41-15-17-2-3-17)29(37)43-26(12-21-22(31)13-36(38)14-23(21)32)19-7-9-25(44-30(33)34)28(10-19)42-16-18-4-5-18/h6-11,13-14,17-18,26,30,35H,2-5,12,15-16H2,1H3/t26-/m0/s1
|
| Chemical Name |
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-(methanesulfonamido)benzoate
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| Synonyms |
CHF6001 CHF 6001 CHF-6001
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4545 mL | 7.2724 mL | 14.5448 mL | |
| 5 mM | 0.2909 mL | 1.4545 mL | 2.9090 mL | |
| 10 mM | 0.1454 mL | 0.7272 mL | 1.4545 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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