5-HT_2A Receptor ( Ki = 0.54 nM )

Lumateperone (2-30 μM) 甲苯磺酸盐具有抗肿瘤活性，并能以剂量依赖性方式抑制细胞增殖[1]。细胞增殖实验[1] 细胞系：RPMI-8226 细胞 浓度：2-30 μM 孵育时间： 结果：抑制细胞生长，IC50 值为17.30 μM。

Lumateperone（腹腔注射，1-10 mg/kg）甲苯磺酸盐以多巴胺 D 1 受体依赖性方式促进 NMDA 和 AMPA 诱导的电流，并增加大鼠 mPFC 切片中多巴胺和谷氨酸的释放 [2]。动物模型：成年雄性Sprague-Dawley大鼠[2] 剂量：1-10 mg/kg 给药方式：腹腔注射 结果：1、3和10 mg/kg浓度20分钟后回避反应受到抑制。促进 NMDA 和 AMPA 敏感电流，还显着增加大鼠 mPFC 视锥细胞中 10 mg/kg 的多巴胺和谷氨酸释放。

Lumateperone能够渗透多药耐药蛋白1（MDR1），并且在7.4的pH下是非常亲脂性的，这是允许抗精神病药物在小肠和血脑屏障中被吸收的特征。Tmax发生在口服给药后3-4小时。

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Lumateperone被广泛代谢。羰基侧链被酮还原酶还原，产生初级活性代谢产物。细胞色素P4503A4酶将lumateperone代谢为2种代谢产物：活性N-去甲基羰基代谢产物（IC200161）或N-去甲基醇代谢产物（IC 200565）。

细胞系：RPMI-8226细胞
浓度：2-30 μM
结果：抑制细胞生长，IC50值为17.30 μM。

Adult male Sprague-Dawley rats
1-10 mg/kg
Intraperitoneal injection

[1]. Identification of Trovafloxacin, Ozanimod, and Ozenoxacin as Potent c-Myc G-quadruplex Stabilizers to Suppress c-Myc Transcription and Myeloma Growth. Mol Inform. 2022 Mar 30:e2200011.

[2]. Lumateperone-mediated effects on prefrontal glutamatergic receptor-mediated neurotransmission: A dopamine D1 receptor dependent mechanism. Eur Neuropsychopharmacol. 2022 Jul 22;62:22-35.

Pharmacodynamics
Lumateperone, also known as ITI-007, is an atypical antipsychotic that has proven to be effective in the treatment of schizophrenia. Lumateperone's receptor binding profile is unique, allowing it to target schizophrenia related symptoms while minimizing adverse effects. In contrast to other second generation antipsychotics such as [lurasidone] and [brexpiprazole], lumateperone behaves as a partial agonist and as an antagonist at pre and postynaptic dopamine (D2) receptors respectively. Patients with moderate or severe hepatic impairment (Child-Pugh class B or C) tend to have higher plasma concentrations of lumateperone than those with normal hepatic function. For this reason, patients with moderate or severe hepatic impairment should receive half the recommended daily dosage.

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Biological Half-Life
Lumateperone's half life is reported to be between 13 to 18 hours. The reported half lives of the metabolites ICI200161 and ICI200131, are 20 and 21 hours respectively.

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Mechanism of Action
There is much to learn about the pathophysiology of schizophrenia; however, dopamine abnormalities, specifically in the prefrontal and mesolimbic brain regions, are consistent in people with schizophrenia. In addition to dopamine, other neurotransmitters such as serotonin, glutamate, GABA and acetylcholine are thought to play a role. Lumateperone is unique among second generation antipsychotics based on its target profile and dopamine D2 receptor occupancy. Unlike other antipsychotics, lumateperone has partial agonist activity at presynaptic dopamine (D2) receptors, resulting in reduced presynaptic release of dopamine, and antagonistic activity at postsynaptic dopamine (D2) receptors. These characteristics allow lumateperone to efficiently reduce dopamine signaling. Lumateperone also targets dopamine (D1) receptors, and a useful secondary result of D1 activation is increased glutamatergic N-methyl-D-aspartate (NMDA) GluN2B receptor phosphorylation. This is significant since NMDA mediated glutamate signaling appears to be impaired in patients who have schizophrenia. Finally, lumateperone is capable of modulating serotonin by inhibiting serotonin transporters (SERT), and by behaving as a 5-HT2A receptor antagonist.

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Hepatotoxicity
In preregistration controlled trials, ALT elevations arose in 2% of patients receiving lumateperone compared to less than 1% of placebo controls. The elevations, however, were usually mild, transient and typically resolved without dose modification or drug discontinuation. In preregistration trials, there were no instances of severe hepatic adverse events, discontinuations because of liver related events or episodes of clinically apparent liver injury with jaundice. Since its approval and more widescale use, there have been no published reports of liver injury with symptoms or jaundice attributed to lumateperone therapy, but clinical experience with its use has been limited. Likelihood score: E (unlikely cause of clinically apparent liver injury).

C24H28FN3O-HCL

393.22

C, 65.82; H, 6.41; F, 3.36; N, 7.43; O, 11.31; S, 5.67

Lumateperone; 313368-91-1

44241743

White to gray solid powder

89.5Ų

LHAPOGAFBLSJJQ-GUTACTQSSA-N

InChI=1S/C24H28FN3O.C7H8O3S/c1-26-14-15-28-21-11-13-27(16-20(21)19-4-2-5-22(26)24(19)28)12-3-6-23(29)17-7-9-18(25)10-8-17;1-6-2-4-7(5-3-6)11(8,9)10/h2,4-5,7-10,20-21H,3,6,11-16H2,1H3;2-5H,1H3,(H,8,9,10)/t20-,21-;/m0./s1

1-(4-fluorophenyl)-4-[(10R,15S)-4-methyl-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-trien-12-yl]butan-1-one;4-methylbenzenesulfonic acid

ITI722; ITI-722; ITI 722; Lumateperone toluenesulfonic acid; Lumateperone PTSA salt; ITI-007; ITI 007; ITI007; Lumateperone, Caplyta; UNII:JIE88N006O; ITI-007 tosylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (~176.8 mM)
H2O: < 0.1 mg/mL

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.42 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.42 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。