BMS-986020 | AM152 | AP-3152 free acid | CAS#1257213-50-5 | LPA1 antagonist

MedKoo Cat#: 526856 | Name: BMS-986020

Description:

WARNING: This product is for research use only, not for human or veterinary use.

BMS-986020, also known as AM152 and AP-3152 free acid, is a potent and selective LPA1 antagonist. BMS-986020 is in Phase 2 clinical development for treating idiopathic pulmonary fibrosis. BMS-986020 selectively inhibits the LPA receptor, which is involved in binding of the signaling molecule lysophosphatidic acid, which in turn is involved in a host of diverse biological functions like cell proliferation, platelet aggregation, smooth muscle contraction, chemotaxis, and tumor cell invasion, among others.

Chemical Structure

BMS-986020

CAS#1257213-50-5

Theoretical Analysis

MedKoo Cat#: 526856

Name: BMS-986020

CAS#: 1257213-50-5

Chemical Formula: C29H26N2O5

Exact Mass: 482.1842

Molecular Weight: 482.54

Elemental Analysis: C, 72.19; H, 5.43; N, 5.81; O, 16.58

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,950.00	Ready to ship
1g	USD 4,650.00	2 weeks
2g	USD 6,650.00	2 weeks

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Related CAS #

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Synonym

BMS-986020; BMS986020; BMS 986020; AP-3152 free acid; AM152; AM 152; AM-152.

IUPAC/Chemical Name

(R)-1-(4'-(3-methyl-4-(((1-phenylethoxy)carbonyl)amino)isoxazol-5-yl)-[1,1'-biphenyl]-4-yl)cyclopropane-1-carboxylic acid

InChi Key

GQBRZBHEPUQRPL-LJQANCHMSA-N

InChi Code

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

SMILES Code

O=C(C1(C2=CC=C(C3=CC=C(C4=C(NC(O[C@H](C)C5=CC=CC=C5)=O)C(C)=NO4)C=C3)C=C2)CC1)O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C7R12B06

QC Data

View QC data: current batch, Lot#C7R12B06

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

BMS-986020 is a high-affinity and selective lysophosphatidic acid receptor 1 (LPA1) antagonist that inhibits bile acid and phospholipid transporters with IC50s of 4.8 µM, 6.2 µM, and 7.5 µM for BSEP, MRP4, and MDR3, respectively.

In vitro activity:

BMS-986020, a high-affinity, selective, small-molecule antagonist of LPA1, is presently in Phase two development for IPF. [18F]BMT-083133, a radioligand targeting LPA1 was developed as a translational research tool for assessment of lung LPA1 engagement of BMS-986020 using in vitro autoradiography (ARG). Sections from healthy and diseased lungs from different species, as well as heterologous cells over-expressing LPA1 were studied. LPA1 target engagement was assessed at various concentrations of BMS-986020 (0.1nM-10nM). Sections and cells were pre-incubated in BMS-986020/buffer solution, followed by incubation with [18F]BMT-083133/BMS-986020/buffer solution and assayed for LPA1 binding using a wash protocol. ~2.6 fold increase in specific [ BMT-083133 binding was detected using ARG in diseased mouse lung compared to healthy mouse lung (187 PSL/mm2 vs. 487 PSL/mm2, p<0.001). A BMS-986020 concentration-dependent displacement of [18F]BMT-083133 binding was observed in LPA1(+) cells and lung sections. At 0.1nM of BMS-986020, the percent displacement in healthy mice, bleomycin mice, and IPF lungs was 18%, 24%, and 31%, respectively; and at 10nM, the percent displacement was 73%, 76%, and 64%, respectively. Thus, BMT-083133 was demonstrated as the first translational radioligand for the assessment of lung LPA1 target engagement using in vitro ARG. Reference: Journal of Nuclear Medicine. Society of Nuclear Medicine; 2014 https://jnm.snmjournals.org/content/55/supplement_1/1207

In vivo activity:

After confirming neuroprotective effects of BMS against acute brain injuries in tMCAO-induced mice, it was next sought to determine whether these effects could be observed against sub-acute brain injuries following ischemic challenge by assessing its effects up to 15 days after tMCAO challenge. BMS was administered either once immediately after reperfusion (single administration) or daily for 14 consecutive days (repeated administration). Repeated BMS administration significantly lowered neurological deficit scores compared to vehicle administration control (Figure 4A). A single administration of BMS also attenuated neurological deficits, although the degree of its effectiveness was smaller than that by repeated administration (Figure 4A). In addition, repeated administration of BMS significantly increased the survival rate of tMCAO-challenged mice compared to the vehicle-administration control (Figure 4B). In the end point of the experiment (15 days after tMCAO), 41.2% of mice survived in the vehicle-administered group (Figure 4B). Single administration of BMS slightly but not significantly increased the survival rate to 53.8% compared to vehicle administration (Figure 4B). However, repeated administration of BMS significantly increased the survival rate to 81.8% (Figure 4B). It was next determined whether BMS administration could attenuate tMCAO-induced brain atrophy. Either single or repeated administration of BMS significantly attenuated the tMCAO-induced brain tissue loss compared to vehicle administration, with more dramatic attenuation by repeated administration (Figure 4C,D). In addition, tMCAO-induced cell apoptosis was dramatically attenuated in the group with repeated administration of BMS, as evidenced by decreased numbers of TUNEL-positive cells (Figure 4E,F). In case of single administration of BMS, the number of TUNEL-positive cells was slightly but significantly reduced compared to that in the vehicleadministered group (Figure 4E,F). Taken together, these data clearly suggest that BMS administration can also exert neuroprotective effects against sub-acute brain injuries in mice following ischemic stroke. Reference: Antioxidants (Basel). 2020 Nov; 9(11): 1097. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695306/

	Solvent	mg/mL	mM
Solubility
	DMSO	62.0	128.49
	Ethanol	58.5	121.23

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 482.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1.Pena A, Kim J, Donnelly D, Murphy B, Shuster D, Watson L, et al. Autoradiographic evaluation of [18F]BMT-083133, a lysophosphatidic acid receptor 1 (LPA1) radioligand. Journal of Nuclear Medicine. Society of Nuclear Medicine; 2014: https://jnm.snmjournals.org/content/55/supplement_1/1207 2. Gaire BP, Sapkota A, Choi JW. BMS-986020, a Specific LPA1 Antagonist, Provides Neuroprotection against Ischemic Stroke in Mice. Antioxidants (Basel). 2020 Nov 8;9(11):1097. doi: 10.3390/antiox9111097. PMID: 33171697; PMCID: PMC7695306.

In vitro protocol:

In vivo protocol:

1.Gaire BP, Sapkota A, Choi JW. BMS-986020, a Specific LPA1 Antagonist, Provides Neuroprotection against Ischemic Stroke in Mice. Antioxidants (Basel). 2020 Nov 8;9(11):1097. doi: 10.3390/antiox9111097. PMID: 33171697; PMCID: PMC7695306.

1: Kihara Y, Mizuno H, Chun J. Lysophospholipid receptors in drug discovery. Exp Cell Res. 2015 May 1;333(2):171-7. doi: 10.1016/j.yexcr.2014.11.020. Epub 2014 Dec 8. Review. PubMed PMID: 25499971; PubMed Central PMCID: PMC4408218.