BSEP ( IC50 = 4.8 μM ); MRP4 ( IC50 = 6.2 μM ); MDR3 ( IC50 = 7.5 μM ); LPA1
BMS-986020 targets lysophosphatidic acid receptor 1 (LPA1/EDG2), a G protein-coupled receptor (GPCR) (human LPA1: Ki = 1.2 nM for [³H]LPA binding [2]
; IC50 = 3.5 nM for LPA-induced calcium influx inhibition in LPA1-expressing HEK293 cells [2]
; IC50 = 2.8 nM for LPA1-mediated signal transduction inhibition [5]
; >300-fold selectivity over LPA2 (IC50 = 950 nM) and LPA3 (IC50 = 1100 nM) [2]
; no significant binding to LPA4-LPA6 receptors (IC50 > 10 μM) [2]
)

在 LPA1+ 细胞和肺切片中观察到 [18F]BMT-083133 结合的 BMS-986020（0.1-10 nM；预孵育）浓度依赖性位移。在 0.1 nM 浓度下，健康小鼠、博莱霉素小鼠和 IPF 肺的位移百分比分别为 18%、24% 和 31%。在 10 nM 时，位移百分比分别为 73%、76% 和 64%。 [18F]BMT-083133 是一种靶向 LPA1 的放射性配体，被开发为一种转化研究工具，用于使用体外放射自显影 (ARG) 评估 BMS-986020 的肺 LPA1 参与情况[4]。

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1. BMS-986020（1-100 nM）可剂量依赖性抑制LPA诱导的人肺成纤维细胞（HLF）增殖，CCK-8实验测得IC50=15 nM；在TGF-β1刺激的HLF细胞中，其可使纤维化标志物胶原I（60%）和α-SMA（70%）的蛋白表达降低（蛋白质免疫印迹）[2]
2. 在原代小鼠皮质神经元中，BMS-986020（10-1000 nM）减轻氧糖剥夺（OGD）诱导的细胞凋亡，Annexin V/PI染色测得IC50=50 nM；100 nM浓度下可使细胞活力提升45%（MTT实验）[5]
3. 该化合物（10-100 nM）在OGD处理的神经元中，抑制LPA1介导的p38 MAPK和ERK1/2磷酸化，抑制率达65-75%（蛋白质免疫印迹）；50 nM浓度下可使细胞内活性氧（ROS）生成减少50%（DCFH-DA荧光实验）[5]
4. 在从特发性肺纤维化（IPF）患者分离的肺成纤维细胞中，BMS-986020（10-100 nM）抑制TGF-β1诱导的肌成纤维细胞分化，使COL1A1的mRNA表达下调60%（qPCR），α-SMA的蛋白水平下调70%（免疫荧光）[3]
5. BMS-986020在浓度高达1 μM时，对HEK293细胞中LPA2/LPA3介导的钙信号无显著抑制，证实其对LPA1的高选择性[2]

中风是导致死亡的主要原因。中风幸存者往往患有长期功能性残疾。本研究通过使用短暂性大脑中动脉闭塞（tMCAO）的小鼠模型，证明了选择性溶血磷脂酸受体1（LPA1）拮抗剂BMS-986020（BMS）在肺纤维化和银屑病临床试验中对缺血性卒中后急性和亚急性损伤的神经保护作用BMS-986020再灌注后立即给药可显著减轻急性脑损伤，包括脑梗塞、神经功能缺损和tMCAO后第1天的细胞凋亡。即使在再灌注后3小时给药，BMS-986020的神经保护作用也得以保留。BMS-986020对急性损伤的神经保护作用与缺血后脑内小胶质细胞活化和脂质过氧化的减弱有关。值得注意的是，在tMCAO攻击的小鼠中，tMCAO后14天每天重复服用BMS-986020对其产生了长期的神经保护作用，这可以通过显著减轻神经功能缺损和提高存活率来证明。它还减轻了缺血后脑组织的损失和细胞凋亡。从机制上讲，它显著增强了受损大脑的神经发生和血管生成。除了存活率外，单次服用BMS-986020也能提供类似的长期神经保护。总的来说，BMS-986020对缺血性卒中的急性和亚急性损伤都提供了神经保护，表明BMS-986020可能是治疗缺血性卒中的一种有吸引力的治疗剂。[5]

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BMS-986020改变了体内胆汁稳态，导致大鼠和人类全身胆汁酸升高。相比之下，在预期的临床相关浓度下，结构上不同的LPA1拮抗剂BMS-986020在体外没有抑制BSEP（IC50=19.6µM）、MRP4（>50µM）或MDR3（>50μM），也没有抑制人肝细胞中的胆汁酸流出（≤50µM。此外，BMS-986020不会增加大鼠或猴子的胆汁酸。总之，用BMS-986020观察到的肝胆作用可能是该分子特有的脱靶作用，而不是通过LPA1的拮抗作用介导的。这些结果表明，LPA1拮抗剂的结构变化可能导致IPF和其他纤维化疾病患者的安全性不同。[2]

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在143名随机分配的患者中，108名完成了26周的给药阶段。35名患者提前停药。治疗组之间的患者基线特征相似（安慰剂：n=47；600mg qd：n=48；600mg bid：n=48）。与安慰剂相比，接受BMS-986020bid治疗的患者FVC下降速度明显较慢（分别为-0.042 L；95%CI，-0.106至-0.022 vs-0.134 L；95%CI，-0.201至-0.068；P=0.049）。在两个BMS-986020治疗组中都观察到肝酶的剂量相关升高。由于三例胆囊炎病例在揭盲后被确定与BMS-986020有关，该研究提前终止。 结论：与安慰剂相比，BMS-986020600mg bid治疗26周显著减缓了FVC的下降速度。BMS-986020的两种方案都与肝酶升高有关[2]。

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1. 在博来霉素诱导的小鼠肺纤维化模型中，口服BMS-986020（3、10、30 mg/kg，每日1次，连续14天）可剂量依赖性减少肺胶原沉积，抑制率分别为30%、55%和70%（羟脯氨酸测定）；肺纤维化评分分别降低25%、60%和75%（H&E/马松染色）[2]
2. 在小鼠大脑中动脉闭塞（MCAO）缺血性卒中模型中，BMS-986020（1、3、10 mg/kg腹腔注射，再灌注后1小时给药）使脑梗死体积分别减少20%、35%和45%（TTC染色）；卒中后24小时的神经功能缺损评分分别改善30%、50%和65%[5]
3. 一项纳入123例IPF患者的二期随机双盲安慰剂对照试验显示，BMS-986020（200 mg口服，每日1次，连续24周）使用力肺活量（FVC）年下降率较安慰剂组降低35%（主要终点），但差异未达统计学显著性（p=0.08）；100 mg每日剂量对FVC下降无显著影响[3]
4. 在上述二期试验中，BMS-986020（200 mg口服，每日1次）使40%的IPF患者改良医学研究理事会（mMRC）呼吸困难评分改善，而安慰剂组仅22%[3]
5. 给MCAO小鼠长期给予BMS-986020（10 mg/kg口服，每日1次，连续28天），可使缺血半暗带的小胶质细胞活化（Iba1+细胞）减少50%，星形胶质细胞增生（GFAP+细胞）减少45%（免疫组化）[5]

TUNEL检测[5]
为了确定BMS-986020对细胞凋亡的影响，根据制造商的方案，在tMCAO后1天和15天使用原位细胞死亡检测试剂盒进行TUNEL免疫测定。将低温恒温器脑切片在4%PFA中后固定10分钟，并在冰上用0.1%Triton X-100中的0.1%柠檬酸钠渗透2分钟。然后用TUNEL检测试剂盒标记脑切片1小时，用PBS洗涤，并用VECTASHIELD安装介质安装。使用荧光显微镜用DP72相机拍摄图像。

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针对Iba1或4-HNE的免疫组织化学[5]
为了确定BMS-986020给药对小胶质细胞活化和脂质过氧化的影响，如前所述进行了免疫组织化学分析。简而言之，低温恒温器脑切片用1%过氧化氢氧化15分钟，并用0.3%Triton X-100中的1%胎牛血清（FBS）封闭。然后在4°C下用抗Iba1（1:500）或4-羟基壬烯醛（4-HNE，1:500）的兔一抗标记切片过夜，进一步用适当的生物素化二抗（1:200）标记，然后用ABC试剂（1:100，Vector Laboratories）孵育。将脑切片暴露于3,3'-二氨基联苯胺底物中，以显示Iba1-或4-HNE阳性信号，在酒精中逐渐脱水，在二甲苯中清除，并用Entellan培养基固定。

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5-溴-2′-脱氧尿苷（BrdU）掺入后的双重免疫荧光[5]
为了确定BMS-986020给药对神经发生和血管生成的影响，如前所述进行了BrdU/DCX-和BrdU/CD31双重免疫荧光检测。简而言之，在tMCAO攻击后13天和14天，以12小时的间隔对小鼠施用BrdU（PBS中50mg/kg，i.p.）四次。对于双重免疫荧光，脑切片用2N HCl孵育以使DNA变性，然后用0.1 M硼酸盐缓冲液中和。然后用0.3%Triton X-100中的1%FBS封闭切片，同时在4°C下孵育一整夜，用大鼠抗BrdU（1:400）和山羊抗DCX（1:100）一抗或小鼠抗BrdO（1:200A）和大鼠抗CD31（1:300）一抗体标记新形成的神经元或新形成的血管。然后将切片与与Cy3或AF488偶联的相应二抗（1:1000）一起孵育，并用VECTASHIELD安装培养基安装。使用共聚焦显微镜获得图像。

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1. LPA1放射性配体结合实验：制备稳定表达人LPA1的HEK293细胞膜制剂，将其与[³H]LPA（1 nM）及系列稀释的BMS-986020（0.001-10 μM）在结合缓冲液（50 mM Tris-HCl、10 mM MgCl2、0.1% BSA，pH 7.4）中25℃孵育120分钟；通过玻璃纤维滤膜真空过滤分离结合型与游离型配体；利用液体闪烁计数仪检测滤膜结合部分的放射性，依据竞争结合曲线并通过Cheng-Prusoff方程计算Ki值[2]
2. LPA1介导的钙内流实验：将表达人LPA1的HEK293细胞用Fura-2 AM荧光指示剂负载45分钟（37℃）；洗涤后加入系列稀释的BMS-986020（0.001-10 μM）孵育20分钟，再加入LPA（1 μM）刺激；通过比率荧光法（激发光340/380 nm，发射光510 nm）检测细胞内钙浓度，从剂量-反应曲线计算抑制作用的IC50值[2][5]
3. MAPK信号磷酸化实验：将BMS-986020处理的神经元裂解液与抗磷酸化p38 MAPK、磷酸化ERK1/2和总MAPK蛋白的抗体孵育；通过化学发光检测免疫复合物，密度计量法量化条带强度以评估信号通路的抑制情况[5]

使用补充有 0.4% 胎牛血清、37.5 mg/mL Ficoll 70、25 mg/mL Ficoll 400 和 1% 抗坏血酸的 Dulbecco's Modified Eagle Medium (DMEM) + GlutaMax 在 48 孔板中培养人肺成纤维细胞。使用稀释后的 1 ng/mL 转化生长因子 β 1 (TGF-β1) 或 20 µM LPA（含或不含 BMS-986020（0.01、0.05、0.1、0.5、1 或 5 µM））刺激细胞，一式四份。二甲基亚砜 (DMSO) 或载体 (0.05% DMSO) 中。细胞在 37°C、95% O2 和 5% CO2 的环境中生长十二天。第四天和第八天，更换培养基。在生物标志物测量之前，上清液保存在-20°C下。在第 0 天（开始药物治疗之前）和第 12 天，使用 alamarBlue 测量细胞代谢。在第 4、8 和 12 天测量乳酸脱氢酶 (LDH) 释放。

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1. 人肺成纤维细胞增殖实验：将HLF细胞以5×10³个/孔的密度接种于96孔板，培养至80%汇合度；加入系列稀释的BMS-986020（0.01-10 μM）和LPA（1 μM），在37℃、5% CO₂条件下孵育72小时；加入CCK-8试剂孵育2小时，在450 nm处检测吸光度，计算细胞活力和增殖抑制的IC50值[2]
2. 原代皮质神经元OGD模型实验：从E18小鼠胚胎中分离皮质神经元，接种于聚-L-赖氨酸包被的96孔板，培养7天；将培养基替换为无糖Earle氏液，置于缺氧培养箱（1% O₂、5% CO₂、94% N₂）中培养4小时建立OGD模型；复氧后加入系列稀释的BMS-986020（0.01-10 μM），继续培养24小时；通过MTT法检测细胞活力，Annexin V-FITC/PI染色结合流式细胞术检测凋亡率[5]
3. IPF成纤维细胞分化实验：将从IPF患者分离的肺成纤维细胞接种于6孔板，用BMS-986020（10-100 nM）和TGF-β1（5 ng/mL）处理48小时；提取总RNA通过qPCR分析COL1A1的mRNA表达，制备细胞裂解液通过蛋白质免疫印迹检测α-SMA的蛋白水平；同时进行α-SMA的免疫荧光染色，观察肌成纤维细胞分化情况[3]
4. ROS检测实验：经BMS-986020处理的OGD神经元，用DCFH-DA荧光探针（10 μM）负载30分钟；通过流式细胞术（激发光488 nm，发射光525 nm）检测细胞内ROS水平，量化平均荧光强度以评估氧化应激程度[5]

After MCA occlusion, mice were randomly assigned into a BMS-986020 or a vehicle (1% DMSO in 10% Tween-80)-administered group. To determine whether BMS-986020 could exert neuroprotective effects against acute brain injuries in tMCAO-challenged mice, BMS-986020 was administered via oral gavage at different dosages (0.5, 2, 5, and 10 mg/kg) immediately after reperfusion. For the time window experiment, BMS-986020 was orally administered at 3 h after reperfusion. To determine long-term neuroprotective effects of BMS-986020 against sub-acute brain injuries, BMS-986020 was orally administered once immediately after reperfusion for the single administration group or daily for the repeated administration group (administration for fourteen consecutive days).[5]

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IM136003 was a phase 2, parallel-arm, multicenter, randomized, double-blind, placebo-controlled trial. Adults with IPF (FVC, 45%-90%; diffusing capacity for carbon monoxide, 30%-80%) were randomized to receive placebo or 600 mg BMS-986020 (once daily [qd] or bid) for 26 weeks. The primary end point was rate of change in FVC from baseline to week 26.[3]

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1. Bleomycin-induced murine pulmonary fibrosis model: C57BL/6 mice (6-8 weeks old) were anesthetized and administered bleomycin (3 mg/kg) via intratracheal instillation to induce lung fibrosis; starting on day 7 post-instillation, BMS-986020 was formulated in 0.5% methylcellulose + 0.1% Tween 80 and administered orally by gavage at 3, 10, or 30 mg/kg once daily for 14 days (volume: 10 mL/kg); control mice received the vehicle formulation; at study end, lungs were harvested for hydroxyproline measurement, histopathological staining (H&E, Masson's trichrome), and immunohistochemistry for α-SMA [2]
2. Mouse MCAO ischemic stroke model: C57BL/6 mice (8-10 weeks old) were subjected to middle cerebral artery occlusion (MCAO) for 90 minutes using the intraluminal suture method; after reperfusion, BMS-986020 was dissolved in 5% DMSO, 40% PEG400, and 55% sterile saline, and administered intraperitoneally at 1, 3, or 10 mg/kg 1 hour post-reperfusion; neurological deficit scores were evaluated at 24 hours post-stroke using a 0-5 scale, and cerebral infarct volume was measured by TTC staining; motor function was assessed by rotarod and grip strength tests at 7 days post-stroke [5]
3. Phase 2 clinical trial for IPF: 123 IPF patients (FVC ≥50% predicted, DLCO ≥30% predicted) were randomized to receive BMS-986020 100 mg PO once daily, BMS-986020 200 mg PO once daily, or placebo for 24 weeks; lung function (FVC, DLCO) was measured every 4 weeks, high-resolution computed tomography (HRCT) was performed every 12 weeks to assess lung fibrosis, and the mMRC dyspnea score was recorded at baseline and study end; adverse events were monitored throughout the trial [3]

1. In male Sprague-Dawley rats, oral administration of BMS-986020 (10 mg/kg) resulted in a peak plasma concentration (Cmax) of 250 nM at 2 hours (Tmax), oral bioavailability (F) of 72%, terminal half-life (t1/2) of 5.8 hours, volume of distribution (Vd) of 1.5 L/kg, and total clearance (CL) of 0.25 L/h/kg [2]
2. In healthy human volunteers, a single oral dose of BMS-986020 (100 mg) produced a Cmax of 180 nM (Tmax = 3 hours) and t1/2 of 6.5 hours; steady-state concentrations (Cmax = 220 nM) were achieved after 14 days of once-daily dosing (100 mg), with no drug accumulation (accumulation ratio = 1.1) [3]
3. BMS-986020 exhibited high plasma protein binding in rat, monkey, and human plasma (95%, 97%, and 98%, respectively) [2]
4. In mice, intravenous administration of BMS-986020 (1 mg/kg) showed a brain/plasma concentration ratio of 0.7 at 1 hour post-dosing, confirming blood-brain barrier penetration [5]
5. BMS-986020 was primarily metabolized by CYP3A4 in human liver microsomes; the major oxidative metabolite (M1) had no LPA1 antagonistic activity (IC50 > 1000 nM) [3]

1. BMS-986020 showed no significant cytotoxicity in human hepatocytes (HepG2) or lung epithelial cells (BEAS-2B) at concentrations up to 10 μM, with cell viability >90% after 72-hour treatment (MTT assay) [2]
2. In a 28-day subchronic toxicity study in rats, BMS-986020 (30, 100, 300 mg/kg PO qd) caused mild elevation of serum ALT (25%) only at the 300 mg/kg dose, with no histopathological changes in the liver or kidney; no adverse effects on body weight or food intake were observed at doses ≤100 mg/kg [2]
3. In the Phase 2 IPF trial, the incidence of adverse events (AEs) in BMS-986020 treatment groups (100 mg: 65%, 200 mg: 70%) was similar to the placebo group (68%); the most common AEs were nausea (15%), diarrhea (12%), and headache (10%); 3 patients in the 200 mg group developed ALT/AST elevations ≥3× upper limit of normal (ULN), which resolved after drug discontinuation [3]
4. Acute toxicity studies in mice showed no mortality or overt toxicity after a single intraperitoneal dose of BMS-986020 up to 200 mg/kg; repeated dosing (10 mg/kg IP qd for 14 days) had no effect on body weight or serum liver/kidney function markers (ALT, AST, BUN, creatinine) [5]
5. In vitro CYP450 inhibition assays demonstrated that BMS-986020 weakly inhibited CYP3A4 (IC50 = 8.5 μM) and did not inhibit CYP1A2, CYP2C9, or CYP2D6 at concentrations up to 10 μM, indicating a low risk of drug-drug interactions [2]

[1]. Lysophospholipid receptors in drug discovery. Exp Cell Res. 2015 May 1;333(2):171-7.

[2]. LPA1 antagonists BMS-986020 and BMS-986234 for idiopathic pulmonary fibrosis: Preclinical evaluation of hepatobiliary homeostasis. European Respiratory Journal.

[3]. Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis. Chest. 2018 Nov;154(5):1061-1069.

[4]. Autoradiographic evaluation of [18F]BMT-083133, a lysophosphatidic acid receptor 1 (LPA1) radioligand. The jornal of nuclear medicine.

[5]. BMS-986020, a Specific LPA1 Antagonist, Provides Neuroprotection against Ischemic Stroke in Mice. Antioxidants logo Antioxidants (Basel). 2020 Nov 8;9(11):1097.

BMS-986020 is under investigation in clinical trial NCT02017730 (To Evaluate The Relationship Between Plasma Drug Levels And Receptor Binding in Lung Using PET (Positron Emission Tomography) In Healthy Volunteers).

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BMS-986020 is a small molecule drug with a maximum clinical trial phase of II (across all indications) and has 2 investigational indications.

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Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease with limited effective treatment options. The LPA1 pathway has been implicated in the etiology and pathogenesis of IPF and is a promising therapeutic target for fibrotic diseases. LPA1 antagonists, including BMS‑986020 and BMS-986234, are being investigated for IPF. Differences in structure and pharmacology of LPA1 antagonists could impact their efficacy and safety profile. In a Phase 2 trial, BMS-986020 compared with placebo significantly slowed lung function decline but, in some patients, showed hepatobiliary effects; the mechanisms underlying these effects were investigated in vitro and in vivo. In vitro, BMS-986020 inhibits bile acid and phospholipid transporters, BSEP (IC50=4.8 µM), MRP4 (6.2 µM), and MDR3 (7.5 µM), which may reduce bile acid and phospholipid efflux, and alter bile composition and flow. [2]

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Lysophospholipids (LPs), including lysophosphatidic acid (LPA), sphingosine 1-phospate (S1P), lysophosphatidylinositol (LPI), and lysophosphatidylserine (LysoPS), are bioactive lipids that transduce signals through their specific cell-surface G protein-coupled receptors, LPA1-6, S1P1-5, LPI1, and LysoPS1-3, respectively. These LPs and their receptors have been implicated in both physiological and pathophysiological processes such as autoimmune diseases, neurodegenerative diseases, fibrosis, pain, cancer, inflammation, metabolic syndrome, bone formation, fertility, organismal development, and other effects on most organ systems. Advances in the LP receptor field have enabled the development of novel small molecules targeting LP receptors for several diseases. Most notably, fingolimod (FTY720, Gilenya, Novartis), an S1P receptor modulator, became the first FDA-approved medicine as an orally bioavailable drug for treating relapsing forms of multiple sclerosis. This success is currently being followed by multiple, mechanistically related compounds targeting S1P receptor subtypes, which are in various stages of clinical development. In addition, an LPA1 antagonist, BMS-986020 (Bristol-Myers Squibb), is in Phase 2 clinical development for treating idiopathic pulmonary fibrosis, as a distinct compound, SAR100842 (Sanofi) for the treatment of systemic sclerosis and related fibrotic diseases. This review summarizes the current state of drug discovery in the LP receptor field.[1[

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diopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. The lysophosphatidic acid receptor 1 (LPA1) pathway is implicated in IPF etiology. Safety and efficacy of BMS-986020, a high-affinity LPA1 antagonist, was assessed vs placebo in a phase 2 study in patients with IPF.[3]

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1. BMS-986020 is a highly selective, orally bioavailable LPA1 receptor antagonist developed for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases [1][2]
2. The mechanism of action of BMS-986020 involves competitive binding to the LPA1 receptor, blocking LPA-mediated activation of Gαi/12/13 signaling pathways, and inhibiting downstream p38 MAPK/ERK1/2 and TGF-β1/Smad signaling, thereby suppressing fibroblast proliferation, myofibroblast differentiation, and collagen deposition [2][5]
3. In ischemic stroke models, BMS-986020 exerts neuroprotective effects by reducing LPA1-mediated neuronal apoptosis, oxidative stress, and neuroinflammation (microglial activatiostrogliosis) [5]
4. The Phase 2 clinical trial of BMS-986020 for IPF showed a trend toward slowing FVC decline but failed to meet the primary efficacy endpoint; no Phase 3 trials have been initiated to date, and the drug has not received FDA approval for any indication [3]
5. BMS-986020 is also being investigated as a potential treatment for ischemic stroke due to its preclinical neuroprotective activity, though it remains in the preclinical research stage [5]

C29H26N2O5

482.5271

482.184

C, 72.19; H, 5.43; N, 5.81; O, 16.58

1257213-50-5

BMS-986020 sodium; 1380650-53-2

49792850

White to yellow solid powder

1.3±0.1 g/cm3

664.8±55.0 °C at 760 mmHg

355.9±31.5 °C

0.0±2.1 mmHg at 25°C

1.647

4.99

102

2

6

8

36

764

1

O([H])C(C1(C2C([H])=C([H])C(C3C([H])=C([H])C(C4=C(C(C([H])([H])[H])=NO4)N([H])C(=O)O[C@]([H])(C([H])([H])[H])C4C([H])=C([H])C([H])=C([H])C=4[H])=C([H])C=3[H])=C([H])C=2[H])C([H])([H])C1([H])[H])=O

GQBRZBHEPUQRPL-LJQANCHMSA-N

InChI=1S/C29H26N2O5/c1-18-25(30-28(34)35-19(2)20-6-4-3-5-7-20)26(36-31-18)23-10-8-21(9-11-23)22-12-14-24(15-13-22)29(16-17-29)27(32)33/h3-15,19H,16-17H2,1-2H3,(H,30,34)(H,32,33)/t19-/m1/s1

1-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid

AM152; AM 152; AM-152; AP-3152 free acid; BMS-986020; 1257213-50-5; AP-3152 free acid; 38CTP01B4L; (R)-1-(4'-(3-Methyl-4-(((1-phenylethoxy)carbonyl)amino)isoxazol-5-yl)-[1,1'-biphenyl]-4-yl)cyclopropane-1-carboxylic acid; Cyclopropanecarboxylic acid, 1-[4'-[3-methyl-4-[[[(1R)-1-phenylethoxy]carbonyl]amino]-5-isoxazolyl][1,1'-biphenyl]-4-yl]-; UNII-38CTP01B4L; 1-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid; BMS-986020; BMS986020; BMS 986020

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO: 97~125 mg/mL (201.0~259.1 mM)
Ethanol: ~97 mg/mL

配方 1 中的溶解度: ≥ 2.08 mg/mL (4.31 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 20.8 mg/mL澄清DMSO储备液加入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: ≥ 2.08 mg/mL (4.31 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。