In vitro: VU6005649 is a CNS penetrant mGlu7/8 receptor agonist with EC50s of 0.65 μM and 2.6 μM for mGlu7 receptor and mGlu8 receptor, respectively. VU6005649 displays a terminal Kp of 2.43 with total brain levels ~9× above the mGlu7 positive allosteric modulator (PAM) in vitro EC50.
In vivo: When VU6005649 (compound 9f) is dosed at 30 mg/kg IP in 10% Tween 80/H2O (0.75 mg/kg. s.c. amphetamine), no efficacy is observed in this assay. VU6005649 shows modest but significant pro-cognitive effects on associative learning in wild-type mice and the first example of efficacy of an mGlu7/8 positive allosteric modulator (PAM) in this model.
|Animal models||female C57/Bl6 mice|
|Formulation||10% polysorbate 80|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||10 mM in DMSO|
Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines.
Abe M, et al. ACS Med Chem Lett. 2017 Sep 1;8(10):1110-1115. PMID: 29057060.
Fadrozole is a potent, selective and nonsteroidal inhibitor of aromatase with an IC50 of 6.4 nM.
PKM2 inhibitor displays PKM2 inhibitory activity with the IC50 value of 2.95 μM. The IC50 value for PKM1 is 4-5-fold higher than that for PKM2.
CA-4948 is a reversible kinase inhibitor that modulates IRAK4 function in both the toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) signaling cascades, and demonstrates pharmacodynamic and antitumor activity in in vitro and in vivo nonclinical models.
ONC212, a fluorinated-ONC201 analogue, is broadly efficacious across most solid tumors and hematological malignancies in the low nanomolar range and has robust anti-leukemic activity.
JPH203, a selective L-type amino acid transporter 1 inhibitor, shows a dramatic inhibition of leucine uptake (IC50=0.06 µM) and cell growth (IC50=4.1 µM) in human colon cancer cells (HT-29), human oral cancer cells (YD-38) and leukemic cells.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.