| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
ITI214 free base targets phosphodiesterase 1 (PDE1) with a Ki of 58 pM. PDE1 is a dual-substrate phosphodiesterase that hydrolyzes both cAMP and cGMP, and its activity is regulated by calcium/calmodulin. There are three PDE1 isoforms: PDE1A, PDE1B, and PDE1C, each with distinct tissue distribution and substrate preferences. PDE1 is highly expressed in the brain, particularly in areas involved in learning, memory, and mood regulation. By inhibiting PDE1, ITI214 increases intracellular cAMP and cGMP levels, leading to enhanced signaling through PKA, PKG, and the CREB pathway. ITI214 shows excellent selectivity over other PDE family members including PDE2-PDE11.
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| ln Vitro |
According to the study, full-length recombinant r-hPDE1A (Ki= 34 pM), r-hPDE1B (Ki= 380 pM), and r-hPDE1C (Ki= 37 pM) that are transiently expressed in HEK cells may all be successfully inhibited by ITI-214. ..This chemical is over 1000 times more active against the PDE1 isoform and 10,000–300,000 times more selective against all other PDE enzyme families[2] when compared to the closest PDE family enzyme, PDE4D (Ki= 33 nM).
In vitro, ITI214 free base exhibits potent PDE1 inhibitory activity with a Ki of 58 pM. The compound demonstrates excellent selectivity against other PDE family members and against a broad panel of enzymes, receptors, transporters, and ion channels. ITI214 possesses a good overall profile with balanced physicochemical properties, excellent potency and selectivity, and favorable in vitro ADME (absorption, distribution, metabolism, excretion) characteristics. The compound effectively inhibits PDE1-mediated hydrolysis of cAMP and cGMP in cell-based assays, resulting in elevated cyclic nucleotide levels and activation of downstream signaling pathways. ITI214 is a picomolar PDE1 inhibitor with excellent selectivity. |
| ln Vivo |
In tests involving memory, ITI-214 dramatically improved performance at a minimal effective dose of 3 mg/kg[1].
In vivo, ITI214 free base significantly enhances memory performance in cognitive tests with a minimum effective dose of 3 mg/kg. The compound is orally bioavailable and CNS-active, with good brain penetration. In animal models, ITI214 has demonstrated pro-cognitive effects in various behavioral paradigms including novel object recognition, social recognition, and Morris water maze tests. The compound's mechanism of action involves PDE1 inhibition in the brain, leading to increased cAMP/cGMP signaling and enhanced synaptic plasticity. ITI214 also shows potential for treating neuropsychiatric disorders. The compound possesses good pharmacokinetic properties with balanced physicochemical characteristics, supporting its development as a therapeutic candidate. |
| Enzyme Assay |
In vitro enzyme assays for ITI214 free base involve measuring PDE1 activity using recombinant human PDE1 enzymes (PDE1A, PDE1B, PDE1C). The assay is performed in 96- or 384-well plates using a fluorescence polarization or scintillation proximity assay format. [3H]-cAMP or [3H]-cGMP is used as substrate. ITI214 is added at varying concentrations (0.001-1000 nM) and pre-incubated with the enzyme in assay buffer containing calcium and calmodulin. The reaction is initiated by adding the substrate and incubated at 30degC for 30-60 minutes. The reaction is stopped, and the hydrolyzed product is quantified. IC₅0 and Ki values are determined from dose-response curves. Selectivity is assessed by testing ITI214 against PDE2-PDE11 and other enzymes.
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| Cell Assay |
Cellular assays for ITI214 free base are performed using cell lines expressing PDE1 isoforms, such as neuroblastoma cells (SH-SY5Y) or primary neuronal cultures. Cells are cultured in appropriate medium and seeded in 6- or 96-well plates. Cells are treated with serial dilutions of ITI214 (0.001-10 microM) for 1-24 hours. Intracellular cAMP and cGMP levels are measured using ELISA or HTRF-based detection kits. Downstream signaling is assessed by Western blotting for phosphorylated CREB (p-CREB) and other PKA/PKG substrates. Cell viability and proliferation are monitored. The functional activity of ITI214 is confirmed by demonstrating concentration-dependent increases in cyclic nucleotide levels and downstream pathway activation.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat[1]
Doses: 0.1-10 mg/kg Route of Administration: Oral Experimental Results:Memory was Dramatically enhanced in the test at the minimum effective dose of 3 mg/kg. In vivo animal studies for ITI214 free base are conducted in rodent models of cognitive function and neuropsychiatric disorders. Male C57BL/6 mice or Sprague-Dawley rats are administered ITI214 orally at doses of 0.3-30 mg/kg. The novel object recognition test assesses recognition memory: animals are habituated to an open field, exposed to two identical objects, and after a delay, one object is replaced with a novel object. Discrimination ratio is calculated. The Morris water maze tests spatial learning and memory. For pharmacokinetic studies, blood and brain tissue samples are collected at various time points and analyzed by LC-MS/MS. Brain-to-plasma ratios are calculated to assess CNS penetration. Behavioral effects and biomarker changes are correlated with drug exposure. |
| ADME/Pharmacokinetics |
ITI214 free base (CAS#: 1160521-50-5) has molecular formula C2₉H34N₆O2 and molecular weight 498.62. The compound is a solid and is soluble in DMSO. It is a potent PDE1 inhibitor with a Ki of 58 pM, excellent selectivity against other PDE family members, and good oral bioavailability and CNS penetration. ITI214 is a research compound for laboratory use only. The compound is being developed for potential therapeutic applications in cognitive disorders and neuropsychiatric conditions. As of the current date, ITI214 has been evaluated in clinical trials for schizophrenia and other indications.
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| Toxicity/Toxicokinetics |
Toxicological information for ITI214 free base is limited as the compound is a research chemical. Based on its mechanism as a PDE1 inhibitor, potential adverse effects may include those associated with increased cAMP/cGMP signaling, such as cardiovascular effects (hypotension, tachycardia), gastrointestinal disturbances, and CNS effects (headache, dizziness). The compound should be handled with standard laboratory precautions including the use of personal protective equipment and working in a well-ventilated area. Avoid inhalation, ingestion, and skin contact. The compound should be stored at -20degC and disposed of according to institutional guidelines for chemical waste.
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| References | |
| Additional Infomation |
ITI-214 is being studied in the clinical trial NCT03489772 (which studies ITI-214 in healthy volunteers to determine its central nervous system involvement).
ITI214 free base (CAS#: 1160521-50-5) is a potent, orally bioavailable, CNS-active PDE1 inhibitor with a Ki of 58 pM. PDE1 is a calcium/calmodulin-dependent phosphodiesterase that plays a critical role in regulating cAMP and cGMP levels in the brain, and its inhibition has been shown to enhance cognitive function and synaptic plasticity. ITI214 exhibits excellent selectivity against other PDE family members and a broad panel of off-targets. The compound has demonstrated pro-cognitive effects in animal models with a minimum effective dose of 3 mg/kg. ITI214 has been investigated in clinical trials for schizophrenia and cognitive disorders. As of the current date, ITI214 is a research compound and is not approved for therapeutic use. |
| Molecular Formula |
C29H26FN7O
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|---|---|
| Molecular Weight |
507.561448574066
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| Exact Mass |
507.218
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| CAS # |
1160521-50-5
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| Related CAS # |
ITI-214;1642303-38-5
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| PubChem CID |
42639643
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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 |
731.7±70.0 °C at 760 mmHg
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| Flash Point |
396.3±35.7 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.754
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| LogP |
2.57
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
38
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| Complexity |
903
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1C(=O)C2=C(N(N=C2N3C1=N[C@H]4[C@@H]3CCC4)CC5=CC=C(C=C5)C6=NC(=CC=C6)F)NC7=CC=CC=C7
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| InChi Key |
BBIPVJCGIASXJB-PKTZIBPZSA-N
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| InChi Code |
InChI=1S/C29H26FN7O/c1-35-28(38)25-26(31-20-7-3-2-4-8-20)36(34-27(25)37-23-11-5-10-22(23)33-29(35)37)17-18-13-15-19(16-14-18)21-9-6-12-24(30)32-21/h2-4,6-9,12-16,22-23,31H,5,10-11,17H2,1H3/t22-,23+/m1/s1
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| Chemical Name |
(11R,15S)-5-anilino-4-[[4-(6-fluoropyridin-2-yl)phenyl]methyl]-8-methyl-1,3,4,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2,5,9-trien-7-one
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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 | 1.9702 mL | 9.8511 mL | 19.7021 mL | |
| 5 mM | 0.3940 mL | 1.9702 mL | 3.9404 mL | |
| 10 mM | 0.1970 mL | 0.9851 mL | 1.9702 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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