[CAS NO. 1257051-63-0] THPP-1
PRODUCTS SPECIFICATIONS [1257051-63-0]
DESCRIPTION [1257051-63-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 464.90 |
| Molecular Formula | C23H21ClN6O3 |
| SMILES | O=C(C1=C2C=CC=CN2C=N1)N3CCC4=NC(C5=CC=C(N=C5)Cl)=NC(OCCOC)=C4C3 |
Summary
THPP-1, a SGC chemical probe, is a potent and orally bioavailable phosphodiesterase 10A (PDE10A) inhibitor, with K i values of 1 nM and 1.3 nM for human and rat PDE10A, respectively. THPP-1 has excellent pharmacokinetic properties in preclinical species [1] .
IC50 & Target
IC50: 1-1.3 nM (PDE10A) [1] .
In Vivo
THPP-1 (0.1-1.0 mg/kg, p.o.) shows novel object recognition in rats
[1]
.
THPP-1 (p.o., 1-30 mg/kg) dose-dependently increases
phosphorylation of GluR1
S845 in the rat striatum whereas the total levels of GluR1 in the striatum are not affected. Administration of THPP-1 also results in an associated increase in the pGluR1/GluR1 ratios at all doses examined in this study
[1]
.
THPP-1 (1, 3, 10 mg/kg, p.o.) significantly attenuated the stimulant effects in stimulant-induced motor activity (SIMA) in monkey
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male Wistar Hannover rats ranging from 200 to 300 g [1] . |
| Dosage: | 0.1-1.0 mg/kg. |
| Administration: | P.O. |
| Result: | Showed novel object recognition. |
| Animal Model: | Eleven monkeyswere surgically implanted with subcutaneous telemetric devices to permit the simultaneous recording of electrocorticogram (ECoG), electrooculogram (EOG), and electromyogram (EMG) activit |
| Dosage: | 1, 3, 10 mg/kg. |
| Administration: | P.O. |
| Result: | Significantly attenuated the stimulant effects in SIMA. |
| Animal Model: | Male Wistar Hannover rats ranging from 200 to 300 g [1] . |
| Dosage: | 1-30 mg/kg. |
| Administration: | P.O. (10% Tween 80/90% water) 2 h prior to tissue collection ( Pharmacokinetic Analysis ). |
| Result: | Dose-dependently increases phosphorylation of GluR1 S845. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 31.25 mg/mL ( 67.22 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1510 mL | 10.7550 mL | 21.5100 mL |
| 5 mM | 0.4302 mL | 2.1510 mL | 4.3020 mL |
| 10 mM | 0.2151 mL | 1.0755 mL | 2.1510 mL |
References
- [1] Smith SM, et al. The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey. Neuropharmacology. 2013 Jan;64:215-23.
- [2] Vardigan JD, et al. Behavioral and qEEG effects of the PDE10A inhibitor THPP-1 in a novel rhesus model of antipsychotic activity. Psychopharmacology (Berl). 2016 Jul;233(13):2441-50.