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Chemical Structure| 1642303-38-5 Chemical Structure| 1642303-38-5

Structure of ITI-214
CAS No.: 1642303-38-5

Chemical Structure| 1642303-38-5

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ITI-214 is a picomolar PDE1 inhibitor with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters, and ion channels, exhibits potent PDE1 inhibitory activity (Ki = 58 pM).

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Product Details of ITI-214

CAS No. :1642303-38-5
Formula : C29H29FN7O5P
M.W : 605.56
SMILES Code : O=C(C1=C(NC2=CC=CC=C2)N(CC3=CC=C(C4=NC(F)=CC=C4)C=C3)N=C1N56)N(C)C5=N[C@@]7([H])[C@]6([H])CCC7.O=P(O)(O)O
MDL No. :MFCD28385868
InChI Key :ZPIAAFIYOPWWJL-RFPXDPOKSA-N
Pubchem ID :72704434

Safety of ITI-214

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

Description
ITI-214 is a powerful, CNS-penetrant, orally bioavailable inhibitor of PDE1 (with a Ki of 58 pM), boasting remarkable selectivity over other PDE family enzymes as well as a broad spectrum of enzymes, receptors, transporters, and ion channels. It inhibits recombinant full-length human PDE1A, PDE1B, and PDE1C with Ki values of 33 pM, 380 pM, and 35 pM, respectively. ITI-214 has demonstrated effectiveness in various animal models addressing motor and cognitive functions[1][2].

In Vitro:

Cell Line
Concentration Treated Time Description References
P2 rat microglial cells 1 μM 30 minutes enhanced ADP-induced VASP phosphorylation Mol Cell Neurosci. 2020 Jan;102:103449
BV2 cells 10 μM 1 hour inhibited LPS-induced TNF release Mol Cell Neurosci. 2020 Jan;102:103449
rabbit left-ventricular myocytes 1 μM To study the effects of ITI-214 on myocyte contraction and calcium transients, results showed ITI-214 alone did not affect myocyte function or calcium transients. Circulation. 2018 Oct 30;138(18):1974-1987
guinea pig myocytes 1 μM 5 minutes To evaluate the effects of ITI-214 on cardiomyocyte contraction and calcium transients. Results showed ITI-214 did not significantly alter cell shortening or calcium transients in quiescent cells, but enhanced shortening when combined with low-dose adenylate cyclase stimulation in a PKA-dependent manner. Circ Res. 2021 Oct 15;129(9):872-886
adult mouse ventricular cardiomyocytes 1 µM To investigate the effect of PDE1 inhibition on cGMP levels, results showed that ITI-214 alone increased intracellular cGMP levels. Cells. 2023 Dec 3;12(23):2759

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Dog Normal and heart failure dogs Oral or intravenous oral 10 mg/kg or intravenous 0.01 and 0.1 mg/kg Single dose, data measured within 15 minutes post intravenous injection or recorded over two hours post oral administration To assess the cardiovascular effects of ITI-214 in normal and heart failure dogs, results showed ITI-214 increased load-independent contractility, improved relaxation, and reduced systemic arterial resistance, raising cardiac output without altering systolic blood pressure. Circulation. 2018 Oct 30;138(18):1974-1987
Mice MK-801-induced memory impairment model Oral 0.1, 1, 3, 10, 30, 75 mg/kg Single dose, 30 min before testing ITI-214 reversed MK-801-induced working memory impairments in the mouse T-maze continuous alternation task, with a maximal effect of approximately 57% recovery in cognitive function. Br J Pharmacol. 2018 Jul;175(14):3021-3033
Mice Adult mouse ventricular cardiomyocytes In vitro 1 µM To investigate the effect of PDE1 inhibition on cGMP levels and cardiomyocyte contractility, results showed that ITI-214 in combination with CNP or SNP improved cardiomyocyte relaxation. Cells. 2023 Dec 3;12(23):2759
Rats Novel object recognition (NOR) paradigm Oral 0.1-10 mg/kg Single dose, tested 2 hours after administration Evaluate the effect of ITI-214 on memory performance in rats, showing that ITI-214 enhances acquisition, consolidation, and retrieval memory processes Psychopharmacology (Berl). 2016 Sep;233(17):3113-24

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.65mL

0.33mL

0.17mL

8.26mL

1.65mL

0.83mL

16.51mL

3.30mL

1.65mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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