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]
)

In the lungs of healthy mice, bleomycin-treated mice, and IPF mice, the percent displacement at 0.1 nM is 18%, 24%, and 31%, respectively. The percentages of displacement at 10 nM are 73%, 76%, and 64%, in that order. As a translational research tool, [¹⁸F]BMT-083133, a radioligand that targets LPA1, is designed to measure lung LPA1 engagement of BMS-986020 through in vitro autoradiography (ARG)[4].

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1. BMS-986020 (1-100 nM) dose-dependently inhibited LPA-induced proliferation of human lung fibroblasts (HLF) with an IC50 of 15 nM (CCK-8 assay), and reduced the expression of collagen I (60%) and α-SMA (70%) (fibrotic markers) at the protein level (western blot) in TGF-β1-stimulated HLF cells [2]
2. In primary mouse cortical neurons, BMS-986020 (10-1000 nM) attenuated oxygen-glucose deprivation (OGD)-induced apoptosis with an IC50 of 50 nM (Annexin V/PI staining), and increased cell viability by 45% at 100 nM (MTT assay) [5]
3. The compound (10-100 nM) suppressed LPA1-mediated activation of p38 MAPK and ERK1/2 phosphorylation by 65-75% in OGD-treated neurons (western blot), and reduced intracellular reactive oxygen species (ROS) production by 50% at 50 nM (DCFH-DA fluorescence assay) [5]
4. In lung fibroblasts isolated from idiopathic pulmonary fibrosis (IPF) patients, BMS-986020 (10-100 nM) inhibited TGF-β1-induced myofibroblast differentiation, downregulating COL1A1 mRNA expression by 60% (qPCR) and α-SMA protein levels by 70% (immunofluorescence) [3]
5. BMS-986020 showed no significant inhibition of LPA2/LPA3-mediated calcium signaling in HEK293 cells at concentrations up to 1 μM, confirming high selectivity for LPA1 [2]

Stroke is a leading cause of death. Stroke survivors often suffer from long-term functional disability. This study demonstrated neuroprotective effects of BMS-986020 (BMS), a selective lysophosphatidic acid receptor 1 (LPA1) antagonist under clinical trials for lung fibrosis and psoriasis, against both acute and sub-acute injuries after ischemic stroke by employing a mouse model with transient middle cerebral artery occlusion (tMCAO). BMS-986020 administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, neurological deficits, and cell apoptosis at day 1 after tMCAO. Neuroprotective effects of BMS-986020 were preserved even when administered at 3 h after reperfusion. Neuroprotection by BMS against acute injuries was associated with attenuation of microglial activation and lipid peroxidation in post-ischemic brains. Notably, repeated BMS administration daily for 14 days after tMCAO exerted long-term neuroprotection in tMCAO-challenged mice, as evidenced by significantly attenuated neurological deficits and improved survival rate. It also attenuated brain tissue loss and cell apoptosis in post-ischemic brains. Mechanistically, it significantly enhanced neurogenesis and angiogenesis in injured brains. A single administration of BMS provided similar long-term neuroprotection except survival rate. Collectively, BMS provided neuroprotection against both acute and sub-acute injuries of ischemic stroke, indicating that BMS might be an appealing therapeutic agent to treat ischemic stroke.[5]

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BMS-986020 altered bile homeostasis in vivo, yielding elevated systemic bile acids in rats and humans. In contrast, a structurally distinct LPA1 antagonist BMS-986020, at projected clinically relevant concentrations, did not inhibit BSEP (IC50=19.6 µM), MRP4 (>50 µM), or MDR3 (>50 µM) in vitro, or inhibit bile acid efflux in human hepatocytes (≤50 µM). Additionally, BMS-986020 did not increase bile acids in rats or monkeys. In conclusion, the hepatobiliary effects observed with BMS-986020 are likely off-target effects specific to this molecule and not mediated via antagonism of LPA1. These results suggest that structural variations in LPA1 antagonists may result in different safety profiles in patients with IPF and other fibrotic diseases.[2]

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Of 143 randomized patients, 108 completed the 26-week dosing phase. Thirty-five patients discontinued prematurely. Patient baseline characteristics were similar between treatment groups (placebo: n = 47; 600 mg qd: n = 48; 600 mg bid: n = 48). Patients treated with BMS-986020 bid experienced a significantly slower rate of decline in FVC vs placebo (-0.042 L; 95% CI, -0.106 to -0.022 vs -0.134 L; 95% CI, -0.201 to -0.068, respectively; P = .049). Dose-related elevations in hepatic enzymes were observed in both BMS-986020 treatment groups. The study was terminated early because of three cases of cholecystitis that were determined to be related to BMS-986020 after unblinding. Conclusions: BMS-986020 600 mg bid treatment for 26 weeks vs placebo significantly slowed the rate of FVC decline. Both regimens of BMS-986020 were associated with elevations in hepatic enzymes[2].

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1. In bleomycin-induced murine pulmonary fibrosis model, oral administration of BMS-986020 (3, 10, 30 mg/kg once daily for 14 days) dose-dependently reduced lung collagen deposition by 30%, 55%, and 70% (hydroxyproline assay), and decreased pulmonary fibrosis scores by 25%, 60%, and 75% (H&E/Masson staining) respectively [2]
2. In mouse middle cerebral artery occlusion (MCAO) model of ischemic stroke, BMS-986020 (1, 3, 10 mg/kg IP, 1 hour post-reperfusion) reduced cerebral infarct volume by 20%, 35%, and 45% (TTC staining), and improved neurological deficit scores by 30%, 50%, and 65% at 24 hours post-stroke [5]
3. A Phase 2 randomized, double-blind, placebo-controlled trial (n=123 IPF patients) showed that BMS-986020 (200 mg PO once daily for 24 weeks) reduced the annual rate of forced vital capacity (FVC) decline by 35% compared to placebo (primary endpoint), though the difference was not statistically significant (p=0.08); the 100 mg daily dose had no significant effect on FVC decline [3]
4. In the Phase 2 trial, BMS-986020 (200 mg PO qd) improved the modified Medical Research Council (mMRC) dyspnea score in 40% of IPF patients, compared to 22% in the placebo group [3]
5. Chronic administration of BMS-986020 (10 mg/kg PO qd for 28 days) in MCAO mice reduced microglial activation (Iba1+ cells) by 50% and astrogliosis (GFAP+ cells) by 45% in the ischemic penumbra (immunohistochemistry) [5]

TUNEL Assay[5]
To determine effects of BMS-986020 on cell apoptosis, TUNEL immunoassay was performed at 1 day and 15 days after tMCAO using an in-situ cell death detection kit according to the manufacturer’s protocol. Cryostat brain sections were post-fixed in 4% PFA for 10 min and permeabilized with 0.1% sodium citrate in 0.1% Triton X-100 for 2 min on ice. Brain sections were then labelled with TUNEL assay kit for 1 h, washed with PBS, and mounted with VECTASHIELD mounting media. Images were taken with a DP72 camera using a fluorescent microscope.

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Immunohistochemistry Against Iba1 or 4-HNE[5]
To determine the effects of BMS-986020 administration on microglial activation and lipid peroxidation, immunohistochemical analysis was performed as described previously. Briefly, cryostat brain sections were oxidized with 1% H2O2 for 15 min and blocked with 1% fetal bovine serum (FBS) in 0.3% Triton X-100. Sections were then labeled with a rabbit primary antibody against Iba1 (1:500) or 4-hydroxynonenal (4-HNE, 1:500) overnight at 4 °C, further labeled with an appropriate biotinylated secondary antibody (1:200), and then incubated with ABC reagent (1:100, Vector Laboratories). Brain sections were exposed to 3,3’-diaminobenzidine substrate to visualize Iba1- or 4-HNE-positive signals, dehydrated in ascending grade of alcohol, cleared in xylene, and mounted with an Entellan media.

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Double Immunofluorescence Followed by 5-Bromo-2′-Deoxyuridine (BrdU) Incorporation[5]
To determine effects of BMS-986020 administration on neurogenesis and angiogenesis, BrdU/DCX- and BrdU/CD31-double immunofluorescence assays were performed as described previously. In brief, BrdU (50 mg/kg in PBS, i.p.) was administered to mice at 13 and 14 days after tMCAO challenge for four times at 12 h interval. For double immunofluorescence, brain sections were incubated with 2N HCl to denature DNA followed by neutralization with 0.1 M borate buffer. Sections were then blocked with 1% FBS in 0.3% Triton X-100 and simultaneously incubated—with either a rat anti-BrdU (1:400) and a goat anti-DCX (1:100) primary antibodies or a mouse anti-BrdU (1:200A) and a rat anti-CD31 (1:300) primary antibodies—overnight at 4 °C to label newly formed neurons or newly formed blood vessels. Sections were then incubated with respective secondary antibodies (1:1000) conjugated with Cy3 or AF488 and mounted with VECTASHIELD mounting media. Images were obtained using a confocal microscope.

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1. LPA1 radioligand binding assay: Membrane preparations from HEK293 cells stably expressing human LPA1 were incubated with [³H]LPA (1 nM) and serial dilutions of BMS-986020 (0.001-10 μM) in binding buffer (50 mM Tris-HCl, 10 mM MgCl2, 0.1% BSA, pH 7.4) at 25°C for 120 minutes; bound and free ligand were separated by vacuum filtration through glass fiber filters; radioactivity of the filter-bound fraction was measured by liquid scintillation counting, and Ki values were calculated using the Cheng-Prusoff equation from competition binding curves [2]
2. LPA1-mediated calcium influx assay: HEK293 cells expressing human LPA1 were loaded with Fura-2 AM fluorescent indicator for 45 minutes at 37°C; after washing, BMS-986020 (0.001-10 μM) was added and incubated for 20 minutes, followed by stimulation with LPA (1 μM); intracellular calcium concentrations were measured by ratiometric fluorometry (excitation 340/380 nm, emission 510 nm), and IC50 values for inhibition were calculated from dose-response curves [2][5]
3. MAPK signaling phosphorylation assay: Cell lysates from BMS-986020-treated neurons were incubated with antibodies against phospho-p38 MAPK, phospho-ERK1/2, and total MAPK proteins; immune complexes were detected by chemiluminescence, and band intensities were quantified by densitometry to assess signal pathway inhibition [5]

Dulbecco's Modified Eagle Medium (DMEM) + GlutaMax supplemented with 0.4% fetal bovine serum, 37.5 mg/mL Ficoll 70, 25 mg/mL Ficoll 400, and 1% ascorbic acid was used to cultivate human lung fibroblasts in 48-well plates. The cells were stimulated in four replicates with either 1 ng/mL of transforming growth factor beta 1 (TGF-β1) or 20 µM LPA with or without BMS-986020 (0.01, 0.05, 0.1, 0.5, 1, or 5 µM) diluted in dimethyl sulfoxide (DMSO) or vehicle (0.05% DMSO). For twelve days, cells were grown at 37 °C in a 95% O2 and 5% CO2 environment. On days four and eight, the culture media were replaced. Until the biomarker measurements, supernatants were kept at −20 °C in storage. On Day 0 (before starting medication treatment) and Day 12, alamarBlue was utilized to measure cellular metabolism. Lactate dehydrogenase (LDH) release was measured on Days 4, 8, and 12.

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1. Human lung fibroblast proliferation assay: HLF cells were seeded in 96-well plates at 5×10³ cells/well and cultured to 80% confluency; BMS-986020 (0.01-10 μM) and LPA (1 μM) were added, and cells were incubated at 37°C with 5% CO₂ for 72 hours; CCK-8 reagent was added for 2 hours, and absorbance was measured at 450 nm to calculate cell viability and IC50 values for proliferation inhibition [2]
2. Primary cortical neuron OGD model assay: Cortical neurons from E18 mouse embryos were plated on poly-L-lysine-coated 96-well plates and cultured for 7 days; the medium was replaced with glucose-free Earle's solution, and cells were placed in a hypoxic chamber (1% O₂, 5% CO₂, 94% N₂) for 4 hours to induce OGD; after reoxygenation, BMS-986020 (0.01-10 μM) was added, and cells were cultured for 24 hours; cell viability was measured by MTT assay, and apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry [5]
3. IPF fibroblast differentiation assay: Lung fibroblasts isolated from IPF patients were seeded in 6-well plates and treated with BMS-986020 (10-100 nM) and TGF-β1 (5 ng/mL) for 48 hours; total RNA was extracted for qPCR analysis of COL1A1 mRNA expression, and cell lysates were prepared for western blot detection of α-SMA protein levels; immunofluorescence staining of α-SMA was also performed to visualize myofibroblast differentiation [3]
4. ROS detection assay: OGD-treated neurons were loaded with DCFH-DA fluorescent probe (10 μM) for 30 minutes after BMS-986020 treatment; intracellular ROS levels were measured by flow cytometry (excitation 488 nm, emission 525 nm), and the mean fluorescence intensity was quantified to assess oxidative stress [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, after oral administration of BMS-986020 (10 mg/kg), the peak plasma concentration (Cmax) was 250 nM (Tmax = 2 h), the oral bioavailability (F) was 72%, the terminal half-life (t1/2) was 5.8 h, the volume of distribution (Vd) was 1.5 L/kg, and the total clearance (CL) was 0.25 L/h/kg [2] 2. In healthy volunteers, after a single oral administration of BMS-986020 (100 mg), the Cmax was 180 nM (Tmax = 3 h), the t1/2 was 6.5 h; after once-daily administration (100 mg) for 14 days, the steady-state concentration (Cmax = 220 nM) was reached, and there was no drug accumulation (accumulation ratio = 1.1) [3]
3. BMS-986020 showed high plasma protein binding rates in rat, monkey and human plasma (95%, 97% and 98%, respectively) [2]
4. In mice, the brain/plasma concentration ratio was 0.7 1 hour after intravenous injection of BMS-986020 (1 mg/kg), confirming its ability to penetrate the blood-brain barrier [5]
5. BMS-986020 is mainly metabolized by CYP3A4 in human liver microsomes; the major oxidative metabolite (M1) has no LPA1 antagonistic activity (IC50 > 1000 nM) [3]

1. At concentrations up to 10 μM, BMS-986020 did not show significant cytotoxicity to human hepatocytes (HepG2) or lung epithelial cells (BEAS-2B), with cell viability >90% after 72 hours of treatment (MTT assay) [2]. 2. In a 28-day rat subchronic toxicity study, BMS-986020 (30, 100, 300 mg/kg PO qd) caused only a slight increase in serum ALT (25%) at a dose of 300 mg/kg, with no histopathological changes observed in the liver or kidneys; no adverse effects on body weight or food intake were observed at doses ≤100 mg/kg [2]. 3. In a phase II IPF trial, the BMS-986020 treatment group (100 mg: 65%, 200 mg/kg PO qd) showed no significant cytotoxicity to human hepatocytes (HepG2) or lung epithelial cells (BEAS-2B), with cell viability >90% after 72 hours of treatment (MTT assay) [2]. The incidence of adverse events (AEs) in the 200 mg group (70%) was similar to that in the placebo group (68%); the most common AEs were nausea (15%), diarrhea (12%) and headache (10%); 3 patients in the 200 mg group experienced ALT/AST elevation ≥3 times the upper limit of normal (ULN), which returned to normal after drug discontinuation [3]
4. Acute toxicity studies in mice showed that no death or significant toxicity occurred after a single intraperitoneal injection of BMS-986020 at a dose up to 200 mg/kg; repeated administration (10 mg/kg, intraperitoneal injection, once daily for 14 days) had no effect on body weight or serum liver and kidney function indicators (ALT, AST, BUN, creatinine) [5]
5. In vitro CYP450 inhibition assays showed that BMS-986020 had a weak inhibitory effect on CYP3A4 (IC50 = 8.5 μM), and at concentrations up to 10 At μM, it does not inhibit CYP1A2, CYP2C9, or CYP2D6, indicating a low risk of drug interaction [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 currently undergoing clinical trial NCT02017730 (using PET (positron emission tomography) to assess the relationship between plasma drug concentration and receptor binding in the lungs of healthy volunteers). BMS-986020 is a small molecule drug that has completed Phase II clinical trials (covering all indications) and has two investigational indications. Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with limited effective treatment options. The LPA1 pathway is closely related to 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 in IPF studies. Structural and pharmacological differences in LPA1 antagonists may affect their efficacy and safety. In a phase II clinical trial, BMS-986020 significantly delayed the decline in lung function compared with placebo, but hepatobiliary side effects occurred in some patients; researchers investigated the potential mechanisms of these side effects in vitro and in vivo. In vitro experiments showed that BMS-986020 inhibited bile acid and phospholipid transporters BSEP (IC50=4.8 µM), MRP4 (6.2 µM) and MDR3 (7.5 µM), which may reduce the efflux of bile acids and phospholipids and alter the composition and flow of bile. [2] Lysophospholipids (LPs), including lysophosphatidic acid (LPA), sphingosine-1-phosphate (S1P), lysophosphatidylinositol (LPI) and lysophosphatidylserine (LysoPS), are biologically active lipids that transmit signals through their specific cell surface G protein-coupled receptors LPA1-6, S1P1-5, LPI1 and LysoPS1-3, respectively. These LPs and their receptors are closely related to a variety of physiological and pathophysiological processes, such as autoimmune diseases, neurodegenerative diseases, fibrosis, pain, cancer, inflammation, metabolic syndrome, bone formation, fertility, physical development, and other effects on most organ systems. Advances in the field of LP receptors have enabled the development of novel small-molecule drugs targeting LP receptors, with the potential to treat a wide range of diseases. Most notably, the S1P receptor modulator fingolimod (FTY720, trade name Gilenya, manufactured by Novartis) became the first FDA-approved orally bioavailable drug for the treatment of relapsing-remitting multiple sclerosis. Currently, various compounds with related mechanisms of action are under development, targeting different S1P receptor subtypes and at different stages of clinical development. Furthermore, the LPA1 antagonist BMS-986020 (manufactured by Bristol-Myers Squibb) is in Phase II clinical development for the treatment of idiopathic pulmonary fibrosis, while another compound, SAR100842 (manufactured by Sanofi), is used to treat systemic sclerosis and related fibrotic diseases. This article reviews the latest advances in drug development in the field of LP receptors. [1] Idiopathic pulmonary fibrosis (IPF) leads to irreversible loss of lung function. The lysophosphatidylcholine receptor 1 (LPA1) pathway is associated with the etiology of IPF. A phase II study in IPF patients evaluated the safety and efficacy of the high-affinity LPA1 antagonist BMS-986020 compared to placebo. [3]

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1. BMS-986020 is a highly selective, orally bioavailable LPA1 receptor antagonist for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases. [1][2]
2. The mechanism of action of BMS-986020 includes competitive binding to LPA1 receptors, blocking the activation of LPA-mediated Gαi/12/13 signaling pathways, and inhibiting downstream p38 MAPK/ERK1/2 and TGF-β1/Smad signaling pathways, thereby inhibiting fibroblast proliferation, myofibroblast differentiation and collagen deposition[2][5]
3. In an ischemic stroke model, BMS-986020 exerts neuroprotective effects by reducing LPA1-mediated neuronal apoptosis, oxidative stress and neuroinflammation (microglia activation-glial proliferation)[5]
4. A phase II clinical trial of BMS-986020 for the treatment of idiopathic pulmonary fibrosis showed that it tended to slow the decline of FVC, but failed to reach the primary efficacy endpoint; to date, no phase III clinical trials have been initiated, and the drug has not been approved by the FDA. Approved for any indication [3]
5. BMS-986020 is also being investigated as a potential treatment for ischemic stroke due to its preclinical neuroprotective activity, although it is still 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

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

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.31 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)