Details of the Drug

General Information of Drug (ID: DM9SYUT)

• Drug Name: PAMAPIMOD
• Synonyms: Pamapimod; 449811-01-2; RO 4402257; UNII-8S2C9V11K4; Pamapimod (R-1503, Ro4402257); CHEMBL1090089; CHEBI:90685; 8S2C9V11K4; Ro4402257; Ro-4402257; R1503; R 1503; R-1503; 6-(2,4-Difluorophenoxy)-2-{[3-Hydroxy-1-(2-Hydroxyethyl)propyl]amino}-8-Methylpyrido[2,3-D]pyrimidin-7(8h)-One; Pamapimod [USAN:INN]; 6-(2,4-Difluorophenoxy)-2-((3-hydroxy-1-(2-hydroxyethyl)propyl)amino)-8-methylpyrido(2,3-d)pyrimidin-7(8H)-one; 6-(2,4-Difluorophenoxy)-2-[[3-hydroxy-1-(2-hydroxyethyl)propyl]amino]-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Discontinued in Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 406.4
  Topological Polar Surface Area (xlogp); 2.4
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 9
• Chemical Identifiers:
  Formula: C19H20F2N4O4
  IUPAC Name: 6-(2,4-difluorophenoxy)-2-(1,5-dihydroxypentan-3-ylamino)-8-methylpyrido[2,3-d]pyrimidin-7-one
  Canonical SMILES: CN1C2=NC(=NC=C2C=C(C1=O)OC3=C(C=C(C=C3)F)F)NC(CCO)CCO
  InChI: InChI=1S/C19H20F2N4O4/c1-25-17-11(10-22-19(24-17)23-13(4-6-26)5-7-27)8-16(18(25)28)29-15-3-2-12(20)9-14(15)21/h2-3,8-10,13,26-27H,4-7H2,1H3,(H,22,23,24)
  InChIKey: JYYLVUFNAHSSFE-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 16220188
  ChEBI ID: CHEBI:90685
  CAS Number: 449811-01-2
  TTD ID: D04WCI

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[2]

Molecular Expression Atlas of This Drug

• ICD Disease Classification: 15 Disease of the musculoskeletal system/connective tissue
• Disease Class: ICD-11: FA20 Rheumatoid arthritis
• The Studied Tissue: Synovial tissue
• The Studied Disease: Rheumatoid arthritis [ICD-11:FA20]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Stress-activated protein kinase 2a (p38 alpha)	DTT	MAPK14	7.98E-04	1.33	2.48

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 800018538)
• [2] Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J Med Chem. 2010 Mar 25;53(6):2345-53.
• [3] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [4] Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
• [5] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [6] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.