cns penetration

Ganciclovir (2'-Nor-2'-deoxyguanosine) 是核苷类似物和口服抗病毒药物，对CMV 具有抗病毒活性。它用于治疗与艾滋病相关的巨细胞病毒感染的并发症。

RO3 是一种能透过大脑的P2X3和P2X2/3拮抗剂，口服有活性。它对人同型多聚体 P2X3和异型多聚体 P2X2/3受体的 pIC50分别为 5.9 和 7.0。

AC1-IN-1 是 1 型腺苷酸环化酶的选择性抑制剂（AC1，IC50 = 0.54 µM）。

Lamivudine (BCH-189) 是一种核苷逆转录酶抑制剂，可抑制HIV 逆转录酶1和2 以及乙型肝炎病毒的逆转录酶。

(Rac)-VU 6008667 是一种选择性的毒蕈碱乙酰胆碱受体亚型 5（M5 NAM）负异位调节剂，IC50 为 1.8 μM，pIC50 为 5.75，具有较高的中枢神经系统渗透性。

Auglurant is a novel and selective mGlu5 antagonist (IC50: 11 nM (rat) and an IC50: 14 nM (human)). Auglurant has an acceptable CNS penetration.

A-784168 是一种有效的、口服活性的香草素受体 1 型 (TRPV1) 抑制剂。香草素受体 1 型 (TRPV1) 是一种配体门控非选择性阳离子通道，被认为是各种疼痛刺激 (如内源性脂质、辣椒素、热和低 pH 值) 的重要整合剂。口服给药时，A-784168 具有良好的 CNS 渗透性。

Etilevodopa hydrochloride (L-DOPA ethyl ester) 是 Levodopa 的前药，在胃肠道中被非特异性酯酶快速水解产生 Levodopa 和乙醇。Levodopa 是多巴胺的前体，有助于中枢神经系统的渗透和传递多巴胺。Etilevodopa HCl 可用于帕金森病 (PD)的相关研究。

AZ599 is a full agonist of CB1 with good solubility and low CNS penetration.

ML350 (CYM-50202) is a KOR (IC50: 12.6 nM) antagonist with good and moderate selectivity against the DOR and MOR. CYM-50202 displayed high solubility and excellent CNS penetration. CYM-50202 did not display long-lasting pharmacodynamic effects observed wi

AZD7268 is a potent, selective, reversible, and orally bioavailable agonist of δ-opioid receptor with CNS penetration.

GSK-345931A(compound 3)是一种高效和口服活性的RIP2(receptor interacting protein 2)抑制剂，能够抑制多种促炎细胞因子的产生，可用于研究自身免疫性疾病。

WAY267464 is a nonpeptide small-molecule OT agonists with anxiolytic activity. WAY267464 may be used for modulation of potency, selectivity over the structurally similar vasopressin receptors, CNS penetration, and oral bioavailability.

PF-06767832 is a high quality M1 selective PAM (M1 PAM EC50 = 60 nM; M2-M5 PAM EC50 > 10 microM; CNS MPO = 4.9). PF-06767832 has well aligned physicochemical properties, good brain penetration and pharmacokinetic properties. Extensive safety profiling

VU0486321 is a potent mGlu1 PAM with moderate rat PK (CLp = 13.3. mL/min/kg,t1/2 = 54 min), good free fraction (human fu = 0.05, rat fu =0.03) and excellent CNS penetration (Kp = 1.02).

MW-150 hydrochloride (MW01-18-150SRM hydrochloride) is a potent and selective inhibitor of p38α MAPK, with a Ki value of 101 nM. It exhibits excellent CNS penetration and oral bioavailability. MW-150 hydrochloride (MW01-18-150SRM hydrochloride) effectively suppresses the phosphorylation of MK2, a substrate of endogenous p38α MAPK, in activated glial cells.

TTBK1-IN-1(compound 31)是一种强效和选择性的 tau 微管蛋白激酶 1 (TTBK1) 抑制剂(IC50=315 nM)，具有中枢神经(CNS)渗透性，能够抑制疾病相关的Ser 422表位的tau磷酸化，可用于研究阿尔茨海默病。

R-PSOP is a potent and selective nonpeptidic NMUR2 antagonist, exhibiting binding affinity to human and rat NMUR2 with Ki values of 52 nM and 32 nM, respectively. This compound demonstrates moderate central nervous system (CNS) penetration and is valuable in the study of eating disorders, obesity, pain, and stress-related disorders [1].

Rho-Kinase-IN-2 (Compound 23) is an orally active and selective inhibitor of Rho Kinase (ROCK), which can penetrate the central nervous system (CNS). It exhibits a high affinity for ROCK2 with an inhibition constant (IC50) of 3 nM. This compound is of potential interest for further investigations in the field of Huntington's disease research [1].

AM-3189 is a potent and selective GPR40 Agonist with minimal CNS penetration, superior pharmacokinetic properties and in vivo efficacy comparable to AMG 837. AM-3189 maintains the in vivo efficacy of AMG 837 while displaying a superior pharmacokinetic profile and minimal CNS exposure. Similar to AMG 837, while highly potent on GPR40, AM-3189 was highly selective over the closely related GPCRs, GPR41 and GPR43. 13kdemonstrated low clearance, moderate volume of distribution, and good oral bioavailability. AM-3189 does not penetrate the rat CNS as indicated by a rat brain to plasma ratio of 0.04 at 3 h after an oral dose of 5 mg/kg.

VU6007477 是一种具有良好脑穿透性的选择性 M1 型毒蕈碱乙酰胆碱受体正向变构调节剂（positive allosteric modulator，PAM），其 EC50 为 230 nM。与羟基化同系物相比，该化合物表现出更优的中枢神经系统穿透能力，作为人 P-糖蛋白底物具有中等通透性，并具有吡喃酰胺化学骨架。VU6007477 非常适合用于研究强烈的胆碱能癫痫活动、中枢胆碱能信号传导以及需要可靠中枢暴露的神经系统疾病模型。

SHR0687 is a Highly Potent KOR Agonist. SHR0687 showed excellent selectivity over other opioid receptors, such as MOR and DOR. In addition, SHR0687 displayed favorable PK profiles across species, as well as robust in vivo efficacy in a rat carrageenan-induced pain model. Notably, SHR0687 exhibited negligible blood−brain barrier penetration, which was meaningful in minimizing CNS-related side effects.

KOS-1584 is a second-generation epothilone with potential antineoplastic activity. Epothilone KOS-1584 binds to tubulin and induces microtubule polymerization and stabilizes microtubules against depolymerization, which may result in the inhibition of cell division, the induction of G2/M arrest, and apoptosis. Compared to first-generation epothilones, this agent exhibits greater safety and efficacy with an enhanced pharmaceutical profile, including enhanced water solubility and tumor penetration, and reduced CNS exposure. In addition, epothilone KOS-1584 is a poor substrate for the P-glycoprotein (P-gp) drug efflux pump.

Glucosylceramide synthase-IN-4 (compound 12) 是一种高效 GCS 抑制剂，具有 6.8 nM 的 IC50 值。该化合物在人肝细胞中展现出优良的 PK 属性和稳定性。此外，Glucosylceramide synthase-IN-4 还具备较好的中枢神经系统穿透能力和显著的 PXR 选择性。