WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555466
Description: ARRY-797, also known as ARRY-371797, is a potent and selective p38α inhibitor (p38 mitogen-activated protein kinase inhibitor). ARRY-371797 Inhibits LPS-Induced IL-6 and In Vivo Growth of RPMI-8226 Human Multiple Myeloma Cells.
MedKoo Cat#: 555466
Chemical Formula: C22H26F2N4O2
Exact Mass: 416.2024
Molecular Weight: 416.4728
Elemental Analysis: C, 63.45; H, 6.29; F, 9.12; N, 13.45; O, 7.68
Synonym: ARRY-371797; ARRY 371797; ARRY371797; ARRY-797; ARRY 797; ARRY797;
IUPAC/Chemical Name: 5-(2,4-difluorophenoxy)-N-(2-(dimethylamino)ethyl)-1-isobutyl-1H -indazole-6-carboxamide
InChi Key: IFGWYHGYNVGVRB-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H26F2N4O2/c1-14(2)13-28-19-11-17(22(29)25-7-8-27(3)4)21(9-15(19)12-26-28)30-20-6-5-16(23)10-18(20)24/h5-6,9-12,14H,7-8,13H2,1-4H3,(H,25,29)
SMILES Code: O=C(C1=CC2=C(C=C1OC3=CC=C(F)C=C3F)C=NN2CC(C)C)NCCN(C)C
directly inhibited LPS-induced IL-6 production from RPMI-8226 (IC50 = 100 pM) in vitro. In SCID-beige mice, LPS (3 μg/kg) induced IL-6 (7897 ± 827 pg/mL) and TNF-alpha (1922 ± 282 pg/mL) after 2 hours and these cytokines were inhibited by oral administration of ARRY-797 (30 mg/kg) by 91% and 95%, respectively. In MM xenograft models, ARRY-797 (30 mg/kg, BID, PO) inhibited RPMI 8226 tumor growth by 72% as a single agent and by 56% when LPS was administered to stimulate growth in vivo. In addition, ARRY-797 inhibited LPS-induced phosphorylation of p38 in RPMI-8226 xenografts. Together, these data support a role for p38 in IL-6-mediated growth of multiple myelomas. ARRY-797 is the first small molecule p38 inhibitor to demonstrate single agent activity in a MM xenograft model and it has been advanced into preclinical development.
1: Carter D, Warsen A, Mandell K, Cuschieri J, Maier RV, Arbabi S. Delayed topical p38 MAPK inhibition attenuates full-thickness burn wound inflammatory
signaling. J Burn Care Res. 2014 Mar-Apr;35(2):e83-92. doi: 10.1097/BCR.0b013e31828a8d6e. PubMed PMID: 23666384; PubMed Central PMCID: PMC4180234.
2: Muchir A, Wu W, Choi JC, Iwata S, Morrow J, Homma S, Worman HJ. 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. doi: 10.1093/hmg/dds265. Epub 2012 Jul 5. PubMed PMID: 22773734; PubMed Central PMCID: PMC3441127.