Z8526711350

Z8526711350 (also known as 1350 or YVF) is a synthetic cannabinoid from the pyrazolecarboxamide family, developed using an ultra-large-scale docking approach.Z8526711350（又称 1350 或 YVF）是吡唑羧酰胺家族的一种合成大麻素，通过超大规模对接方法开发。

It was developed by screening a library of 12 billion molecules and docking 74 million of these against an in silico model of the CB1 receptor, with the most promising 60 hits prioritised for synthesis.它通过筛选 120 亿分子库并将 7400 万个分子与 CB1 受体的 in silico 模型对接来开发，最有前景的 60 个命中被优先合成。

After two rounds of synthetic modification for increased potency, the active enantiomer Z8526711350 was found to have a CB1 affinity of 0.95 nM, stronger than the reference agonist CP 55,940 used for the docking studies.经过两轮提高效力的合成修饰后，活性对映体 Z8526711350 的 CB1 亲和力为 0.95 nM，比用于对接研究的参考激动剂 CP 55,940 更强。

History and development

• Z8526711350 was developed through an ultra-large-scale docking approach, screening 12 billion molecules and docking 74 million against an in silico CB1 receptor model.Z8526711350 通过超大规模对接方法开发，筛选 120 亿分子并将 7400 万个与 in silico CB1 受体模型对接。
• Of the 74 million docked molecules, 46 were successfully synthesised, of which 9 showed significant affinity to CB1 and two were found to be active as CB1 agonists.在 7400 万个对接分子中，46 个成功合成，其中 9 个对 CB1 显示出显著亲和力，两个被发现为 CB1 激动剂活性化合物。
• ZINC537551486 was initially selected with a CB1 binding affinity of 731 nM and underwent two rounds of synthetic elaboration to increase potency.ZINC537551486 最初以 731 nM 的 CB1 结合亲和力被选中，经过两轮合成优化以提高效力。
• The final active enantiomer, Z8526711350, achieved a CB1 affinity of 0.95 nM, making it stronger than the reference agonist CP 55,940 used in the docking studies.最终活性对映体 Z8526711350 实现了 0.95 nM 的 CB1 亲和力，使其比对接研究中使用的参考激动剂 CP 55,940 更强。
• The compound was reported by Tummino and colleagues in 2025 as part of a Nature Communications study on virtual library docking for cannabinoid-1 receptor agonists.该化合物由 Tummino 及同事于 2025 年作为 Nature Communications 关于大麻素 1 受体激动剂虚拟库对接研究的一部分报告。

• Of the 46 molecules successfully synthesised from the docking screen, 9 showed significant affinity to CB1 and two were found to be active as CB1 agonists with suitable solubility properties.在从对接筛选中成功合成的 46 个分子中，9 个对 CB1 显示出显著亲和力，两个被发现为具有合适溶解性特征的 CB1 激动剂活性化合物。
• The compound was reported by Tummino and colleagues in March 2025 in Nature Communications as part of a study on virtual library docking for cannabinoid-1 receptor agonists.该化合物由 Tummino 及同事于 2025 年 3 月在 Nature Communications 上报告，是关于大麻素 1 受体激动剂虚拟库对接研究的一部分。

Medical uses

• Z8526711350 is a potent analgesic in animal models and showed efficacy against allodynia caused by nerve damage, suggesting potential applications for neuropathic pain.Z8526711350 在动物模型中是强效镇痛药，并显示出对神经损伤引起的异常性疼痛的疗效，提示其对神经病理性疼痛的潜在应用。
• The compound showed reduced levels of sedation and other animal surrogates of psychoactive effects, suggesting functional selectivity at the CB1 receptor.该化合物显示镇静和精神活性效应的其他动物替代指标水平降低，提示其在 CB1 受体上的功能选择性。

Adverse effects

• Z8526711350 was designed to show reduced side effects compared to traditional cannabinoid agonists, with lower levels of sedation observed in animal models.Z8526711350 旨在与传统大麻素激动剂相比显示更少的副作用，在动物模型中观察到较低的镇静水平。

Contraindications and interactions

• Formal contraindications and interaction profiles for Z8526711350 have not been established, as the compound remains in the research stage.由于该化合物仍处于研究阶段，Z8526711350 的正式禁忌症与相互作用资料尚未确立。

Pharmacology

• Z8526711350 is a CB1 receptor agonist with a binding affinity of 0.95 nM for the active enantiomer, making it stronger than the reference compound CP 55,940.Z8526711350 是一种 CB1 受体激动剂，活性对映体的结合亲和力为 0.95 nM，使其比参考化合物 CP 55,940 更强。
• The compound exhibits functional selectivity at the CB1 receptor, showing reduced levels of sedation and other psychoactive effects compared to less selective cannabinoid agonists.该化合物在 CB1 受体上表现出功能选择性，与非选择性大麻素激动剂相比显示较低的镇静和精神活性效应水平。
• In animal models, Z8526711350 demonstrated potent analgesic activity and efficacy against allodynia caused by nerve damage.在动物模型中，Z8526711350 表现出强效镇痛活性和对神经损伤引起的异常性疼痛的疗效。

• The functional selectivity of Z8526711350 at the CB1 receptor, showing reduced sedation and psychoactive effects, represents a significant advance over traditional cannabinoid agonists.Z8526711350 在 CB1 受体上的功能选择性（显示减少的镇静和精神活性效应）代表了相对于传统大麻素激动剂的重大进展。

Chemistry

• Z8526711350 is identified by PubChem CID 170838490 and ChemSpiderID 133323955, and belongs to the pyrazolecarboxamide family of synthetic cannabinoids.Z8526711350 的 PubChem CID 为 170838490，ChemSpiderID 为 133323955，属于合成大麻素的吡唑羧酰胺家族。
• The chemical formula is C20H18F3N3O3S, and the IUPAC name is methyl (2R)-2-[5-methyl-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carbonyl]amino-2-thiophen-2-ylpropanoate.化学式为 C20H18F3N3O3S，IUPAC 名为 (2R)-2-[[5-甲基-1-[3-(三氟甲基)苯基]吡唑-3-羰基]氨基]-2-噻吩-2-基丙酸甲酯。
• The standard InChIKey is XCJKFSDARVULKK-IBGZPJMESA-N, and the molecule contains a trifluoromethylphenyl pyrazole ring connected via a carboxamide linker to a thiophene-containing amino acid ester.标准 InChIKey 为 XCJKFSDARVULKK-IBGZPJMESA-N，分子包含通过羧酰胺连接子连接到含噻吩氨基酸酯的三氟甲基苯基吡唑环。

Society and culture

• Z8526711350 represents a significant advance in synthetic cannabinoid design, using ultra-large-scale computational docking to identify potent CB1 agonists with reduced side effects.Z8526711350 代表了合成大麻素设计的重大进展，使用超大规模计算对接鉴定具有减少副作用的高效力 CB1 激动剂。
• The compound is classified as a designer drug and cannabinoid, reflecting its origins in computational drug design and structural modification.该化合物被归类为设计药物和大麻素，反映其源于计算药物设计与结构修饰。

Availability and economics

• Z8526711350 is a research chemical and has not received regulatory approval for medical use.Z8526711350 是一种研究用化学品，尚未获得医疗用途的监管批准。
• As a compound developed through computational screening, its synthesis has been optimised over two rounds of modification for potency and solubility.作为通过计算筛选开发的化合物，其合成经过两轮修饰优化以提高效力和溶解性。