| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
CI-1044 targets phosphodiesterase 4 (PDE4), a family of enzymes that specifically hydrolyze cyclic AMP (cAMP). It exhibits IC50 values of 0.29 μM for PDE4A5, 0.08 μM for PDE4B2, 0.56 μM for PDE4C2, and 0.09 μM for PDE4D3. By inhibiting PDE4, the compound increases intracellular cAMP levels, which leads to the activation of protein kinase A (PKA) and modulation of inflammatory responses.
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| ln Vitro |
CI-1044 is an orally active PDE4 inhibitor having IC50s of 0.29, 0.08, 0.56, and 0.09 μM for PDE4A5, PDE4B2, PDE4C2, and PDE4D3, respectively. CI-1044 selectively inhibits crude extracts of PDE4 in U937 cells with an IC50 value of 0.27±0.02 μM, which is three times more potent than rolipram (IC50=0.91±0.14) and than cillast (IC50= 0.026±0.007) ten times lower. In the presence of PDE4 inhibitors, TNF-α production decreased in a dose-dependent manner, with average IC50 values of 0.31±0.05 and 0.26±0.05 from three independent trials for CI-1044, cillast and rolipram, respectively. and 0.11±0.01 μM. 1].
In vitro, CI-1044 demonstrates potent inhibition of PDE4 enzymes. The compound's activity against multiple PDE4 subtypes has been characterized in enzyme assays. By increasing cAMP levels in immune cells, CI-1044 suppresses the production of pro-inflammatory cytokines and chemokines. |
| ln Vivo |
Following a solitary oral dosage, TNF-α production was dose-dependently inhibited by CI-1044, rolipram, and cilomilast, with respective ID50 values of 0.4, 1.4, and 1.6 mg/kg. Following multiple oral doses of CI-1044, the ID50 value is equivalent to 0.5 mg/kg. The concentrations of CI-1044 in plasma rose in a proportionate manner within the dose range of 0.1 to 40 mg/kg po (R2=0.878). With an ID50 value of 3.25 mg/kg, CI-1044 dose-dependently inhibits the accumulation of eosinophils in bronchoalveolar lavage (BAL) fluid. A single dose of CI-1044 (10 mg/kg, po) administered 24, 8, 3, or 1 hour prior to the antigen challenge resulted in a 6%, 56%, 48%, and 79% suppression of BAL eosinophil counts [1].
In vivo, CI-1044 has been evaluated in preclinical models of inflammatory diseases. As an orally active PDE4 inhibitor, it has demonstrated efficacy in reducing inflammation in various animal models. The compound's ability to modulate immune responses makes it a candidate for treating inflammatory and respiratory diseases. |
| Enzyme Assay |
In vitro enzyme assays for PDE4 inhibition involve incubating recombinant PDE4 subtypes (PDE4A5, PDE4B2, PDE4C2, PDE4D3) with cAMP substrate and varying concentrations of CI-1044. The hydrolysis of cAMP to AMP is measured using a scintillation proximity assay or a luminescent AMP detection method. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cellular assays are performed using immune cells such as peripheral blood mononuclear cells (PBMCs) or macrophages. Cells are stimulated with LPS or other inflammatory stimuli in the presence of CI-1044 at various concentrations. Cytokine production (TNF-α, IL-6, IL-10) is measured by ELISA to assess the anti-inflammatory effects of PDE4 inhibition. Intracellular cAMP levels may also be measured to confirm target engagement.
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| Animal Protocol |
In vivo studies are conducted in animal models of inflammatory diseases, such as LPS-induced endotoxemia, asthma, or chronic obstructive pulmonary disease (COPD). CI-1044 is administered orally, and inflammatory markers in serum or bronchoalveolar lavage fluid are measured. Lung histology may be evaluated for assessment of inflammation and tissue damage.
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| ADME/Pharmacokinetics |
CI-1044 (molecular weight 422.48, formula C₂₃H₂₆N₄O₄) is a small-molecule compound. It is orally active and soluble in DMSO. The compound is typically stored at -20°C. Its physicochemical properties support oral bioavailability and favorable drug-like characteristics.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have evaluated CI-1044 in animal models. As a PDE4 inhibitor, its toxicity profile is related to the class-specific side effects, including gastrointestinal disturbances (nausea, vomiting) and potential cardiovascular effects. The compound has demonstrated a manageable safety profile in preclinical studies.
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| References | |
| Additional Infomation |
CI-1044 (PD-189659) is a PDE4 inhibitor developed for the treatment of inflammatory diseases. Its mechanism involves inhibition of PDE4, leading to increased intracellular cAMP levels and suppression of pro-inflammatory cytokine production. The compound has been studied for its potential in treating respiratory and inflammatory conditions. Despite promising preclinical activity, CI-1044 has not received regulatory approval for clinical use.
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| Molecular Formula |
C23H19N5O2
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|---|---|
| Molecular Weight |
397.429264307022
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| Exact Mass |
397.153
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| CAS # |
197894-84-1
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| PubChem CID |
9843744
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
773.2±60.0 °C at 760 mmHg
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| Flash Point |
421.4±32.9 °C
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| Vapour Pressure |
0.0±2.6 mmHg at 25°C
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| Index of Refraction |
1.750
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| LogP |
0.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
704
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CN2C(=O)[C@@H](N=C(C3=CC(=CC1=C32)N)C4=CC=CC=C4)NC(=O)C5=CN=CC=C5
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| InChi Key |
XGXOSJSGDNPEEF-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C23H19N5O2/c24-17-11-15-8-10-28-20(15)18(12-17)19(14-5-2-1-3-6-14)26-21(23(28)30)27-22(29)16-7-4-9-25-13-16/h1-7,9,11-13,21H,8,10,24H2,(H,27,29)/t21-/m0/s1
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| Chemical Name |
(R)-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-3-yl)nicotinamide
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| Synonyms |
PD-189659; PD 189659; PD189659; CI-1044; CI 1044; CI1044; UNII-O4T475XIIY.
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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 : ~125 mg/mL (~314.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.23 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 (5.23 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5162 mL | 12.5808 mL | 25.1617 mL | |
| 5 mM | 0.5032 mL | 2.5162 mL | 5.0323 mL | |
| 10 mM | 0.2516 mL | 1.2581 mL | 2.5162 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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