Details of the Drug

General Information of Drug (ID: DMXD93K)

Drug Name
ARRY-614
Synonyms
Pexmetinib; 945614-12-0; ARRY-614; Pexmetinib (ARRY-614); UNII-3750D0U8B5; 3750D0U8B5; Pexmetinib [INN]; Pexmetinib;ARRY-614; Pexmetinib(ARRY-614); ARRY614; SCHEMBL379035; GTPL9917; MolPort-039-193-822; LNMRSSIMGCDUTP-UHFFFAOYSA-N; BCP28410; EX-A1421; s7799; ZINC41747181; AKOS032945154; SB16914; Urea, N-(3-(1,1-dimethylethyl)-1-(4-methylphenyl)-1H-pyrazol-5-yl)-N'-((5-fluoro-2-((1-(2-hydroxyethyl)-1H-indazol-5-yl)oxy)phenyl)methyl)-
Indication
Disease Entry ICD 11 Status REF
Arthritis FA20 Discontinued in Phase 1 [1]
Myelodysplastic syndrome 2A37 Discontinued in Phase 1 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 556.6
Topological Polar Surface Area (xlogp) 5.3
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C31H33FN6O3
IUPAC Name
1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[[5-fluoro-2-[1-(2-hydroxyethyl)indazol-5-yl]oxyphenyl]methyl]urea
Canonical SMILES
CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC3=C(C=CC(=C3)F)OC4=CC5=C(C=C4)N(N=C5)CCO
InChI
InChI=1S/C31H33FN6O3/c1-20-5-8-24(9-6-20)38-29(17-28(36-38)31(2,3)4)35-30(40)33-18-22-15-23(32)7-12-27(22)41-25-10-11-26-21(16-25)19-34-37(26)13-14-39/h5-12,15-17,19,39H,13-14,18H2,1-4H3,(H2,33,35,40)
InChIKey
LNMRSSIMGCDUTP-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
24765037
CAS Number
945614-12-0
TTD ID
D0ML0L

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Angiopoietin 1 receptor (TEK) TT9VGXW TIE2_HUMAN Modulator [2]
Stress-activated protein kinase (p38) TTWELHI NOUNIPROTAC Modulator [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026289)
2 Cmpany report (Arraybiopharma)
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38alpha inhibitor. Bioorg Med Chem Lett. 2013 May 15;23(10):3028-33.
5 Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.
6 Evaluation of WO2012032067 and WO2012055846: two selective PI3Kdelta inhibitors, which is GSK-2269557. Expert Opin Ther Pat. 2012 Aug;22(8):965-70.
7 Inhibition of Wnt/beta-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Idelta/ . Chem Biol. 2011 Apr 22;18(4):485-94.
8 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7959).
9 US patent application no. 2008,0269,123, Methods for treating polycystic kidney disease (pkd) or other cyst forming diseases.
10 The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83.
11 US patent application no. 2008,0119,498, Therapeutic agent for pruritus comprising p38 map kinase inhibitor as the active ingredient.
12 p38 MAPK inhibitors ameliorate target organ damage in hypertension: Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension. J Pharmacol Exp Ther. 2003 Dec;307(3):932-8.
13 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
14 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
15 Clinical pipeline report, company report or official report of Deciphera Pharmaceuticals.
16 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1842).
17 Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
18 Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8.
19 Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I. Bioorg Med Chem Lett. 2000 Oct 2;10(19):2167-70.