Details of the Drug

General Information of Drug (ID: DMP0N4U)

• Drug Name: PD173074

Indication

Disease Entry	ICD 11	Status	REF
Nasopharyngeal carcinoma	2B6B	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 523.7
  Topological Polar Surface Area (xlogp); 4.5
  Rotatable Bond Count (rotbonds); 13
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C28H41N7O3
  IUPAC Name: 1-tert-butyl-3-[2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea
  Canonical SMILES: CCN(CC)CCCCNC1=NC2=NC(=C(C=C2C=N1)C3=CC(=CC(=C3)OC)OC)NC(=O)NC(C)(C)C
  InChI: InChI=1S/C28H41N7O3/c1-8-35(9-2)13-11-10-12-29-26-30-18-20-16-23(19-14-21(37-6)17-22(15-19)38-7)25(31-24(20)32-26)33-27(36)34-28(3,4)5/h14-18H,8-13H2,1-7H3,(H3,29,30,31,32,33,34,36)
  InChIKey: DXCUKNQANPLTEJ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 1401
  ChEBI ID: CHEBI:63448
  CAS Number: 219580-11-7
  TTD ID: D0VF6E

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fibroblast growth factor receptor (FGFR)	TT0LF7H	NOUNIPROTAC	Antagonist	[2]
Fusion protein FGFR3-TACC3 (FGFR3-TACC3)	TTFPD8J	FGFR3_HUMAN-TACC3_HUMAN	Inhibitor	[1]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Nasopharyngeal carcinoma
• ICD Disease Classification: 2B6B

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Proto-oncogene c-Src (SRC)	DTT	SRC	6.45E-01	-0.08	-0.58
Proto-oncogene c-Src (SRC)	DTT	SRC	2.08E-03	-0.52	-1.62

References

• [1] Recurrent FGFR3-TACC3 fusion gene in nasopharyngeal carcinoma.Cancer Biol Ther. 2014;15(12):1613-21.
• [2] Tumor angiogenesis as a therapeutic target. Drug Discov Today. 2001 Oct 1;6(19):1005-1024.
• [3] Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD166285 and PD173074: implications for combination treatment with photodynamic therapy. Invest New Drugs. 1999;17(2):121-35.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [5] TAS-120, a highly potent and selective irreversible FGFR inhibitor, is effective in tumors harboring various FGFR gene abnormalities. Molecular Cancer Therapeutics. 01/2014; 12(11_Supplement):A270-A270.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther. 2014 Nov;13(11):2547-58.
• [8] Preclinical profile of BAY 1163877 - a selective pan-FGFR inhibitor in phase 1 clinical trial. Cancer Research. 10/2014; 74(19 Supplement):1739-1739.
• [9] Clinical pipeline report, company report or official report of InnoCare Pharma.
• [10] 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.
• [11] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [12] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [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] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [16] Clinical pipeline report, company report or official report of Turning Point Therapeutics.