Details of the Drug

General Information of Drug (ID: DMFZXI2)

• Drug Name: NVP-TAE684
• Synonyms: 761439-42-3; NVP-TAE684; NVP-TAE 684; TAE684; TAE-684; 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidine-2,4-diamine; TAE684 (NVP-TAE684); TAE 684; UNII-EH1713MN4K; CHEMBL509032; EH1713MN4K; 5-Chloro-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-2,4-pyrimidinediamine; C30H40ClN7O3S

Indication

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 614.2
  Logarithm of the Partition Coefficient (xlogp); 5.7
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 10
• Chemical Identifiers:
  Formula: C30H40ClN7O3S
  IUPAC Name: 5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine
  Canonical SMILES: CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC
  InChI: InChI=1S/C30H40ClN7O3S/c1-21(2)42(39,40)28-8-6-5-7-26(28)33-29-24(31)20-32-30(35-29)34-25-10-9-23(19-27(25)41-4)37-13-11-22(12-14-37)38-17-15-36(3)16-18-38/h5-10,19-22H,11-18H2,1-4H3,(H2,32,33,34,35)
  InChIKey: QQWUGDVOUVUTOY-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 16038120
  ChEBI ID: CHEBI:91338
  CAS Number: 761439-42-3
  TTD ID: D0R2WK

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Insulin receptor (INSR)	TTCBFJO	INSR_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ALK tyrosine kinase receptor (ALK)	OTV3P4V8	ALK_HUMAN	Drug Response	[3]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Drug Response	[3]
GRB2-associated-binding protein 1 (GAB1)	OTQKE6V4	GAB1_HUMAN	Post-Translational Modifications	[4]
Hepatocyte growth factor (HGF)	OTGHUA23	HGF_HUMAN	Drug Response	[4]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[5]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[5]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Drug Response	[4]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Drug Response	[4]
Protransforming growth factor alpha (TGFA)	OTPD1LL9	TGFA_HUMAN	Drug Response	[4]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Post-Translational Modifications	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Lymphoma
• ICD Disease Classification: 2A80-2A86

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Insulin receptor (INSR)	DTT	INSR	1.03E-05	0.26	0.66

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: 5714).
• [2] Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5.
• [3] A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 2011 Sep 15;71(18):6051-60. doi: 10.1158/0008-5472.CAN-11-1340. Epub 2011 Jul 26.
• [4] Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells. Clin Cancer Res. 2012 Jul 1;18(13):3592-602. doi: 10.1158/1078-0432.CCR-11-2972. Epub 2012 May 2.
• [5] Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40. doi: 10.1073/pnas.1019559108. Epub 2011 Apr 18.