| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
ITI-214 targets phosphodiesterase 1 (PDE1), a family of enzymes that hydrolyze cAMP and cGMP. It inhibits PDE1A, PDE1B, and PDE1C with Ki values of 33 pM, 380 pM, and 35 pM, respectively. It shows >1,000-fold selectivity over PDE4 and other PDE isoforms.
|
|---|---|
| ln Vitro |
ITI-214 is 10,000–300 times more selective against all other PDE family enzymes and over 1000 times more active against the PDE1 isoform than PDE4D (Ki= 33 nM), the next closest PDE family enzyme. 000 instances[2].
ITI-214 inhibits recombinant full-length human PDE1A, PDE1B, and PDE1C with Kis of 33 pM, 380 pM, and 35 pM, respectively. It has a Ki of 58 pM from bovine brain. It exhibits potent PDE1 inhibitory activity. |
| ln Vivo |
ITI-214 considerably boosted memory performance in tests with the lowest effective dose of 3 mg/kg[1].
In vivo, ITI-214 shows good efficacy. It is a CNS-active, orally bioavailable inhibitor. Its ability to penetrate the central nervous system makes it suitable for treating cognitive disorders. It is currently under investigation for various indications. |
| Enzyme Assay |
The primary assay for PDE1 inhibition is an enzyme activity assay using purified recombinant PDE1 enzymes. The hydrolysis of a fluorescent or radiolabeled substrate (cAMP or cGMP) is measured in the presence of the compound. The Ki value is determined from the inhibition curve.
|
| Cell Assay |
In vitro cellular assays for ITI-214 involve treating cells with the compound and measuring the increase in intracellular cAMP or cGMP levels. These assays confirm the compound's ability to inhibit PDE1 activity in a cellular context and its functional effects on downstream signaling pathways.
|
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [1]
Doses: 0.1-10 mg/kg Route of Administration: po Experimental Results: Memory performance was Dramatically enhanced at the lowest effective dose of 3 mg/kg. In vivo efficacy of ITI-214 is evaluated in animal models of cognitive impairment, such as rodent models of schizophrenia or Alzheimer's disease. Its effects on cognition, memory, and other behavioral parameters are assessed. Its pharmacokinetic and pharmacodynamic properties are characterized in these models. |
| ADME/Pharmacokinetics |
ITI-214 is an orally bioavailable and CNS-penetrant compound. It has a Ki of 58 pM and shows excellent selectivity. Its pharmacokinetic profile supports once-daily dosing. It is currently in clinical development, and its properties are well-characterized.
|
| Toxicity/Toxicokinetics |
Toxicological data for ITI-214 is not detailed in the provided sources. As it is in clinical development, it has undergone extensive preclinical safety evaluations. Its safety and tolerability are being assessed in human clinical trials.
|
| References |
|
| Additional Infomation |
See also: Iti-214 (Note moved to).
ITI-214 is a potent and selective PDE1 inhibitor in clinical development for the treatment of cognitive impairment. Its high selectivity for PDE1 over other PDE families is a key feature that differentiates it from other PDE inhibitors. It represents a promising therapeutic approach for neuropsychiatric and neurodegenerative disorders. |
| Molecular Formula |
C29H29FN7O5P
|
|---|---|
| Molecular Weight |
605.5672
|
| Exact Mass |
605.195
|
| CAS # |
1642303-38-5
|
| Related CAS # |
ITI-214 free base;1160521-50-5
|
| PubChem CID |
72704434
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
43
|
| Complexity |
953
|
| Defined Atom Stereocenter Count |
2
|
| 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.OP(=O)(O)O
|
| InChi Key |
(6aR,9aS)-2-(4-(6-fluoropyridin-2-yl)benzyl)-5-methyl-3-(phenylamino)-5,6a,7,8,9,9a-hexahydrocyclopenta[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one phosphate
|
| InChi Code |
ZPIAAFIYOPWWJL-RFPXDPOKSA-N
|
| Chemical Name |
(6aR,9aS)-2-(4-(6-fluoropyridin-2-yl)benzyl)-5-methyl-3-(phenylamino)-5,6a,7,8,9,9a-hexahydrocyclopenta[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one phosphate
|
| Synonyms |
ITI-214 ITI 214 ITI214 ITI-214 phosphate salt
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 30 mg/mL (~49.54 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.13 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 25.0 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: ≥ 2.5 mg/mL (4.13 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6513 mL | 8.2567 mL | 16.5134 mL | |
| 5 mM | 0.3303 mL | 1.6513 mL | 3.3027 mL | |
| 10 mM | 0.1651 mL | 0.8257 mL | 1.6513 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
