Drug Information

Drug (ID: DG01182) and It's Reported Resistant Information

• Name: Panobinostat
• Synonyms: Panobinostat; 404950-80-7; LBH589; LBH-589; Farydak; Panobinostat (LBH589); Faridak; LBH 589; (E)-N-Hydroxy-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylamide; NVP-LBH589; NVP-LBH-589; UNII-9647FM7Y3Z; LBH-589B; CHEBI:85990; 9647FM7Y3Z; 404950-80-7 (free base); (E)-N-HYDROXY-3-(4-{[2-(2-METHYL-1H-INDOL-3-YL)-ETHYLAMINO]-METHYL}-PHENYL)-ACRYLAMIDE; (E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide; panobinostat hydrate; Farydak (TN); (2E)-N-hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]acrylamide; (2E)-N-hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enamide; (E)-N-hydroxy-3-(4-((2-(2-methyl-1H-indol-3-yl)ethylamino)methyl)phenyl)acrylamide; 2-Propenamide, N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-, (2E)-; Panobinostat [USAN:INN]; 2-Propenamide, N-hydroxy-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)-, (2E)-; Panobinostat(LBH589); LBH589 - Panobinostat; Panobinostat (USAN/INN); N-Hydroxy-3-[4-[2-(2-methyl-1H-indol-3-yl)ethylaminomethyl]phenyl]-2(E)-propenamide; MLS006011216; NVP-LBH 589; SCHEMBL164801; SCHEMBL183197; CHEMBL483254; GTPL7489; SCHEMBL22773814; BDBM29589; CHEBI:93774; DTXSID40193506; EX-A169; N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]-2-propenamide; BCPP000187; BDBM198124; AOB87727; BCP01816; LBH58,9NVP-LBH589,Panobinostat; (LBH-589); MFCD09833242; NSC761190; s1030; ZINC22010649; AKOS005146046; BCP9000844; CCG-208762; CS-0267; DB06603; EX-8456; NSC-761190; (2E)-N-Hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide; (E)-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enehydroxamic acid; NCGC00263117-05; NCGC00263117-07; 2-Propenamide, N-hydroxy-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino) methyl)phenyl)-, (2E)-; AC-28652; AM808102; AS-17046; HY-10224; QC-10419; SMR004702978; DB-025426; SW219369-1; W6096; EC-000.2287; A25218; D10319; J-523585; Q7131441; BRD-K02130563-001-07-2; (E)-N-Hydroxy-3-[4-[[[2-(2-methyl-1H-indole-3-yl)ethyl]amino]methyl]phenyl]acrylamide; N-hydroxy-3 -[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide; N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide; Panobinostat;(E)-N-hydroxy-3-(4-((2-(2-methyl-1H-indol-3-yl)ethylamino)methyl)phenyl)acrylamide
• Indication:
  In total 3 Indication(s)
  Multiple myeloma [ICD-11: 2A83]; Approved; [1]
  Primary myelofibrosis [ICD-11: 2A20]; Approved; [1]
  Type-2 diabetes [ICD-11: 5A11]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Brain cancer [ICD-11: 2A00]; [1]
• Target: Histone deacetylase 1 (HDAC1); HDAC1_HUMAN; [1]
• Formula: C21H23N3O2
• IsoSMILES: CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)/C=C/C(=O)NO
• InChI: 1S/C21H23N3O2/c1-15-18(19-4-2-3-5-20(19)23-15)12-13-22-14-17-8-6-16(7-9-17)10-11-21(25)24-26/h2-11,22-23,26H,12-14H2,1H3,(H,24,25)/b11-10+
• InChIKey: FPOHNWQLNRZRFC-ZHACJKMWSA-N
• PubChem CID: 6918837
• ChEBI ID: CHEBI:85990
• TTD Drug ID: D0E3SH
• VARIDT ID: DR00181
• DrugBank ID: DB06603

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Quinolinate phosphoribosyltransferase (QPRT) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: MG-63 cells; Bone; Homo sapiens (Human); CVCL_0426
• In Vitro Model: MMQ cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_2117
• In Vitro Model: MOLM-13 cells; Peripheral blood; Homo sapiens (Human); CVCL_2119
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: SH-1-V8 cells; Esophagus; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis; RNA-sequencing analysis
• Experiment for Drug Resistance: Flow cytometry
• Mechanism Description: RNA-sequencing identifies quinolinic acid phosphoribosyltransferase (QPRT) as a highly expressed gene in bortezomib-panobinostat resistant U87 cells. QPRT, an enzyme catalyzing the rate-determining conversion of quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) a precursor for de novo NAD+ biosynthesis from tryptophan.

References

• Ref 1: Targeting NAD(+) Biosynthesis Overcomes Panobinostat and Bortezomib-Induced Malignant Glioma Resistance .Mol Cancer Res. 2020 Jul;18(7):1004-1017. doi: 10.1158/1541-7786.MCR-19-0669. Epub 2020 Apr 1. 10.1158/1541-7786.MCR-19-0669