VU0364770

MCE 的所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务。

VU0364770

CAS No. : 61350-00-3

MCE 国际站：VU0364770

产品活性：VU0364770 是一种有效的选择性 mGlu4 正变构调节剂 (PAM)。VU0346770 对大鼠 mGlu4 和人 mGlu4 受体的 EC₅₀ 分别为 290 nM 和 1.1 μM。VU0364770 对 mGlu5 具有拮抗活性，EC₅₀ 为 17.9 μM，VU0364770 对 mGlu6 具有正变构调节活性，EC₅₀ 为 6.8 μM。VU0364770 还对 MAO 具有活性，作用于人 MAO-A 和 MAO-B 的 K_i 值分别为8.5 和 0.72 μM。

研究领域：GPCR/G Protein  |  Neuronal Signaling

作用靶点：mGluR

In Vitro: VU0364770 is a selective positive allosteric modulator of mGlu₄ in recombinant systems. VU0364770 is a potent PAM of multiple signaling pathways that enhances the response of the rat and human mGlu₄ receptors to the endogenous agonist glutamate. VU0364770 produces a concentration-dependent potentiation of the response to an EC₂₀ concentration of glutamate with EC₅₀ of 1.1±0.2 μM and increases the maximal response to glutamate from 100 to 227±17%. Because of concerns that this chemical scaffold might possess activity at MAO, full IC₅₀ determinations is performed for VU0364770 at the MAO-A and MAO-B isoforms; these studies result in K_is of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively. When tested at a 10 μM concentration at each mGlu receptor, VU0364770 exhibits weak PAM activity (4.3-fold left shift of the glutamate CRC) at mGlu6 and antagonist activity (3.3-fold right shift of the glutamate CRC) at mGlu5 (compare to the 16.5-fold left shift of the glutamate concentration-response for mGlu₄ at 10 μM). When further evaluated in a full concentration-response curve format, VU0364770 exhibits antagonist activity at mGlu₅ with a potency of 17.9±5.5 μM and PAM activity at mGlu₆ with a potency of 6.8±1.7 μM (compare with the potency of VU0364770 on the rat mGlu₄ receptor of 290±80 nM).

In Vivo: VU0364770 exhibits suitable pharmacokinetic properties for systemic dosing in animal models. After intravenous administration, VU0364770 is rapidly clears from the systemic circulation (165 ml/min/kg) and exhibits a volume of distribution of 2.92 L/kg. VU0364770 is a highly protein-bound ligand displaying free fractions of 2.7 and 1.8% in human and rat plasma, respectively. VU0364770 also shows an improved pharmacokinetic profile relative to previously reported mGlu₄ PAMs with enhanced central penetration and a total brain-to-plasma ratio of more than 1 after systemic administration of a 10 mg/kg dose. VU0364770 produces a dose-dependent reversal of haloperidol-induced catalepsy. VU0364770 dose-dependently reverses haloperidol (0.75 mg/kg)-induced catalepsy in rats, significant at doses of 10 to 56.6 mg/kg, after subcutaneous dosing (F_6,69=8.04; p<0.001).

相关产品：Bioactive Compound Library Plus  |  GPCR/G Protein Compound Library  |  Neuronal Signaling Compound Library  |  Neurotransmitter Receptor Compound Library  |  Heterocyclic Compound Library  |  Membrane Protein-targeted Compound Library  |  Membrane Receptor-targeted Compound Library  |  Highly Selective Activators Library  |  L-Glutamine  |  LY341495  |  Ro 67-7476  |  Xanthurenic acid  |  DHPG  |  Eglumegad  |  MPEP Hydrochloride  |  MTEP hydrochloride  |  CHPG sodium salt  |  CTEP  |  JNJ16259685  |  (RS)-MCPG  |  LY2794193  |  LY367385 hydrochloride  |  LY404039  |  O-Phospho-L-serine  |  Mavoglurant  |  Dipraglurant  |  NPS 2390  |  MMPIP hydrochloride  |  MSOP  |  RO0711401  |  AMN082  |  Basimglurant  |  Foliglurax monohydrochloride  |  JNJ-40411813

热门产品线：重组蛋白  |  化合物库  |  天然产物  |  荧光染料  |  PROTAC  |  同位素标记物

Trending products：Recombinant Proteins  |  Bioactive Screening Libraries  |  Natural Products  |  Dye Reagents  |  PROTAC  |  Isotope-Labeled Compounds