Emprumapimod (PF-07265803) is an orally bioactive, selective p38α MAPK inhibitor that directly inhibits LPS-induced IL-6 production in RPMI-8226 cells (IC50=100 pM). Emprumapimod is indicated for the study of dilated cardiomyopathy and acute inflammatory pain.

Physicochemical Properties

Molecular Formula	C24H29F2N5O3
Molecular Weight	473.515572309494
Exact Mass	473.223
CAS #	765914-60-1
Related CAS #	Emprumapimod hydrochloride
PubChem CID	67411502
Appearance	White to off-white solid powder
LogP	3.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	10
Heavy Atom Count	34
Complexity	698
Defined Atom Stereocenter Count	1
SMILES	N1(CC(C)C)C2=C(C=C(OC3=CC=C(F)C=C3F)C(C(N[C@H](C(N)=O)CCN(C)C)=O)=C2)C=N1
InChi Key	JOOOJNJPZINWHM-IBGZPJMESA-N
InChi Code	InChI=1S/C24H29F2N5O3/c1-14(2)13-31-20-11-17(24(33)29-19(23(27)32)7-8-30(3)4)22(9-15(20)12-28-31)34-21-6-5-16(25)10-18(21)26/h5-6,9-12,14,19H,7-8,13H2,1-4H3,(H2,27,32)(H,29,33)/t19-/m0/s1
Chemical Name	N-[(2S)-1-amino-4-(dimethylamino)-1-oxobutan-2-yl]-5-(2,4-difluorophenoxy)-1-(2-methylpropyl)indazole-6-carboxamide
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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

Targets	p38α
ln Vitro	With an IC50 value of 100 pM, emprumapimod (ARRY-797) suppresses the production of IL-6 in RPMI-8226 cells stimulated by LPS[1].
ln Vivo	Emprumapimod (ARRY-797) (30 mg/kg; oral) decreases the expression of p38 in RPMI-8226 xenografts and IL-6 (91%) and TNF-α (95%) in SCID-beige mice. In multiple myeloma (MM) xenograft models, phosphorylation of RPMI-8226 inhibits tumor growth (72%)[1]. In LmnaH222P/H222P mice, eremapimod (30 mg/kg; oral; twice daily for 4 weeks) inhibits the development of LV fractional shortening (FS) and left ventricular dilatation[2].
Animal Protocol	Animal/Disease Models: LmnaH222P/H222P mice were[2] Doses: 30 mg/kg Route of Administration: Administered orally by gavage starting when mice were 16 weeks of age and continuing until 20 weeks of age Experimental Results: There were significant increases in LVEDD and LVESD as well as a decrease in FS, a parameter directly proportional to the LV ejection fraction.
References	[1]. ARRY-797, a Potent and Selective Inhibitor of p38 Map Kinase, Inhibits LPS-Induced IL-6 and In Vivo Growth of RPMI-8226 Human Multiple Myeloma Cells. [2]. Abnormal p38α mitogen-activated protein kinase signaling in dilated cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet. 2012 Oct 1;21(19):4325-33.
Additional Infomation	Emprumapimod is a potent, orally active and selective inhibitor of p38α mitogen-activated kinase inhibitor. It was investigated for dilated cardiomyopathy.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (211.18 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 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 25.0 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: ≥ 2.5 mg/mL (5.28 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 25.0 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: ≥ 2.5 mg/mL (5.28 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 25.0 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	2.1118 mL	10.5592 mL	21.1184 mL
	5 mM	0.4224 mL	2.1118 mL	4.2237 mL
	10 mM	0.2112 mL	1.0559 mL	2.1118 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.