Details of the Drug

General Information of Drug (ID: DMUP5Z0)

Drug Name
Nirogacestat
Synonyms
PF-03084014; 1290543-63-3; PF-03084014; PF-3084014; UNII-QZ62892OFJ; 865773-15-5; PF 3084014; PF-03084014 (PF-3084014); QZ62892OFJ; Z-3181; PF03084014; Nirogacestat [USAN]; Nirogacestat (USAN/INN); GTPL7746; SCHEMBL13184754; CHEMBL1770916; EX-A855; DTXSID60235679; MolPort-039-193-852; (2S)-2-[[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]amino]-N-[1-[1-(2,2-dimethylpropylamino)-2-methylpropan-2-yl]imidazol-4-yl]pentanamide; ZINC38217837; s8018; AKOS030526383; SB16726; DB12005; CS-1689; NCGC00378713-01
Indication
Disease Entry ICD 11 Status REF
Desmoid tumour 2F7C Approved [1]
Alzheimer disease 8A20 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 2 [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 489.6
Logarithm of the Partition Coefficient (xlogp) 4.8
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C27H41F2N5O
IUPAC Name
(2S)-2-[[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]amino]-N-[1-[1-(2,2-dimethylpropylamino)-2-methylpropan-2-yl]imidazol-4-yl]pentanamide
Canonical SMILES
CCC[C@@H](C(=O)NC1=CN(C=N1)C(C)(C)CNCC(C)(C)C)N[C@H]2CCC3=C(C2)C(=CC(=C3)F)F
InChI
InChI=1S/C27H41F2N5O/c1-7-8-23(32-20-10-9-18-11-19(28)12-22(29)21(18)13-20)25(35)33-24-14-34(17-31-24)27(5,6)16-30-15-26(2,3)4/h11-12,14,17,20,23,30,32H,7-10,13,15-16H2,1-6H3,(H,33,35)/t20-,23-/m0/s1
InChIKey
VFCRKLWBYMDAED-REWPJTCUSA-N
Cross-matching ID
PubChem CID
46224413
CAS Number
1290543-63-3
DrugBank ID
DB12005
TTD ID
D00GPQ
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Gamma-secretase (GS) TT9W8GU APH1A_HUMAN ; APH1B_HUMAN ; PEN2_HUMAN ; NICA_HUMAN ; PSN1_HUMAN Modulator [4]
Amyloid beta A4 protein (APP) TTE4KHA A4_HUMAN Inhibitor [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Gene/Protein Processing [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [5]
Transcription factor HES-1 (HES1) OT8P19W2 HES1_HUMAN Gene/Protein Processing [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Desmoid tumour
ICD Disease Classification 2F7C
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Amyloid beta A4 protein (APP) DTT APP 1.60E-02 -0.07 -0.31
Gamma-secretase (GS) DTT APH1A; APH1B; NCSTN; PSENEN; PSEN1 1.47E-02 -0.09 -0.37
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 217677
2 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: 7746).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014.J Pharmacol Exp Ther.2010 Jul;334(1):269-77.
5 NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.