BMS-P5 free base is a specific, orally bioactive inhibitor of peptide arginine diiminase 4 (PAD4). BMS-P5 free base blocks the formation of NETs induced by multiple myeloma and delays tumor progression.

Physicochemical Properties

Molecular Formula	C27H32N6O2
Molecular Weight	472.581985473633
Exact Mass	472.26
Elemental Analysis	C, 68.62; H, 6.83; N, 17.78; O, 6.77
CAS #	1550371-22-6
Related CAS #	BMS-P5;1549811-36-0
PubChem CID	118158953
Appearance	White to off-white solid powder
LogP	2.6
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	35
Complexity	779
Defined Atom Stereocenter Count	2
SMILES	C[C@H]1CC[C@H](CN1C(=O)C2=CC3=C(C(=C2)OC)N(C(=N3)C4=CC5=C(N4CC6CC6)N=CC=C5)C)N
InChi Key	PXJXCBYHGJEEJH-OXJNMPFZSA-N
InChi Code	InChI=1S/C27H32N6O2/c1-16-6-9-20(28)15-32(16)27(34)19-11-21-24(23(13-19)35-3)31(2)26(30-21)22-12-18-5-4-10-29-25(18)33(22)14-17-7-8-17/h4-5,10-13,16-17,20H,6-9,14-15,28H2,1-3H3/t16-,20+/m0/s1
Chemical Name	[(2S,5R)-5-amino-2-methylpiperidin-1-yl]-[2-[1-(cyclopropylmethyl)pyrrolo[2,3-b]pyridin-2-yl]-7-methoxy-1-methylbenzimidazol-5-yl]methanone
Synonyms	BMS-P5 free base; BMS-P5; BMSP5; BMS P5;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Histone H3 citrullination produced by calcium ionophore is inhibited by BMS-P5 [1]. Additionally, MM production of NETs caused by primary MM cells can be inhibited by BMS-P5 [1].
ln Vivo	The incidence rate of tumor-bearing tumors is markedly elevated by BMS-P5 (50 mg/kg, gavage) [1]. Tumor-promoting proteins in the tumor microenvironment may be destroyed by BMS-P5 (50 mg/kg, gavage), which would delay the growth of the tumor in
Cell Assay	Cell viability assay [1]. Cell Types: neutrophils. Tested Concentrations: 10 µM and 100 µM. Incubation Duration: 30 minutes, then add DP42 or 5TGM1 CM. Experimental Results: Prevention of MM-induced NET formation.
Animal Protocol	Animal/Disease Models: MM syngeneic mouse model [1]. Doses: 50 mg/kg. Route of Administration: Starting from the 3rd day after injection of tumor cells, po (oral gavage) was given twice a day. Experimental Results: Dramatically delayed symptom development and Dramatically prolonged survival of MM-bearing mice.
References	[1]. A Novel Peptidylarginine Deiminase 4 (PAD4) Inhibitor BMS-P5 Blocks Formation of Neutrophil Extracellular Traps and Delays Progression of Multiple Myeloma. Mol Cancer Ther. 2020 Jul;19(7):1530-1538.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~529.01 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.40 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.40 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1160 mL	10.5802 mL	21.1604 mL
	5 mM	0.4232 mL	2.1160 mL	4.2321 mL
	10 mM	0.2116 mL	1.0580 mL	2.1160 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.