Details of the Drug

General Information of Drug (ID: DMEOS5K)

• Drug Name: AEE-788
• Synonyms: AEE; AEE 788; AEE788; GNF-Pf-5343; AEE-788, NVP-AEE 788, AEE788

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1], [2]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 440.6
  Topological Polar Surface Area (xlogp); 4.6
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C27H32N6
  IUPAC Name: 6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
  Canonical SMILES: CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4N[C@H](C)C5=CC=CC=C5
  InChI: InChI=1S/C27H32N6/c1-3-32-13-15-33(16-14-32)18-21-9-11-23(12-10-21)25-17-24-26(28-19-29-27(24)31-25)30-20(2)22-7-5-4-6-8-22/h4-12,17,19-20H,3,13-16,18H2,1-2H3,(H2,28,29,30,31)/t20-/m1/s1
  InChIKey: OONFNUWBHFSNBT-HXUWFJFHSA-N
• Cross-matching ID:
  PubChem CID: 10297043
  CAS Number: 497839-62-0
  DrugBank ID: DB12558
  TTD ID: D0G2QH

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fibroblast growth factor receptor 2 (FGFR2)	TTGJVQM	FGFR2_HUMAN	Inhibitor	[3]
Fibroblast growth factor receptor 3 (FGFR3)	TTST7KB	FGFR3_HUMAN	Inhibitor	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Solid tumour/cancer
• ICD Disease Classification: 2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Fibroblast growth factor receptor 3 (FGFR3)	DTT	FGFR3	5.83E-03	0.08	0.1
Fibroblast growth factor receptor 2 (FGFR2)	DTT	FGFR2	4.82E-01	-0.03	-0.2

References

• [1] 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: 7643).
• [2] ClinicalTrials.gov (NCT00107237) AEE788 and Everolimus in Treating Patients With Recurrent or Relapsed Glioblastoma Multiforme. U.S. National Institutes of Health.
• [3] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [5] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [6] Keratinocyte growth factor. Expert Opin Biol Ther. 2009 Jun;9(6):779-87.
• [7] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [8] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Company report (Eli Lilly) (drug: LY2874455)
• [11] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [12] National Cancer Institute Drug Dictionary (drug id 751593).
• [13] Corrigendum to 'Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models' [Eur J Cancer 61 (2016) 20-28]. Eur J Cancer. 2017 Jan;70:156.
• [14] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia. PLoS One. 2020 Dec 28;15(12):e0244368.
• [17] Clinical pipeline report, company report or official report of Genentech (2011).