Panobinostat

Base Information

• Chemical Name: Panobinostat
• CAS No.: 404950-80-7
• Molecular Formula: C21H23N3O2
• Molecular Weight: 349.433
• Hs Code.: 29339900
• European Community (EC) Number: 803-814-1
• UNII: 9647FM7Y3Z
• DSSTox Substance ID: DTXSID40193506
• Nikkaji Number: J2.554.199E,J3.451.397J
• Wikipedia: Panobinostat
• Wikidata: Q7131441
• NCI Thesaurus Code: C66948
• RXCUI: 1603350
• Pharos Ligand ID: DV83J283Y51H
• Metabolomics Workbench ID: 149853
• ChEMBL ID: CHEMBL483254
• Mol file: 404950-80-7.mol

Synonyms:Farydak;LBH 589;LBH589;NVP LBH589;NVP-LBH589;panobinostat

Chemical Property of Panobinostat

Chemical Property:

• Appearance/Colour: Yellow solid
• Melting Point: 114-117?C
• Refractive Index: 1.682
• PKA: 8.71±0.23(Predicted)
• PSA: 77.15000
• Density: 1.241 g/cm³
• LogP: 4.10900
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility.: Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 5 mg/ml with warming).
• XLogP3: 3
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 7
• Exact Mass: 349.17902698
• Heavy Atom Count: 26
• Complexity: 474

Purity/Quality:

Panobinostat ^*data from reagent suppliers

Safty Information:

• Statements: 22-36/37/38-20
• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)C=CC(=O)NO
• Isomeric SMILES: CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)/C=C/C(=O)NO
• Recent ClinicalTrials: Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma
• Recent EU Clinical Trials: Efficacy of daratumumab (Dara) retreatment using a histone deacetylase-inhibitor (HDACi: panobinostat) as a Dara-longevity-inducing, epigenetic agent in combination with bortezomib-dexamethasone as a quadruplet in relapsed / refractory multiple myeloma (RRMM) patients
• Description: Panobinostat is a potent inhibitor of all histone deacetylases (HDACs), with Ki values ranging from 0.6 to 31 nM for HDAC1-11. Through this action, it leads to acetylation of a range of cellular proteins, resulting in cell cycle arrest and apoptosis in cancer cells. It has potential applications in several different forms of cancer as well as in spinal muscular atrophy and HIV therapy.
• Uses: The novel labelled histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells.
• Clinical Use: Histone deacetylase (HDAC) inhibitor: Treatment of relapsed and/or refractory multiple myeloma
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: avoid with dextromethorphan possibly increased risk of ventricular arrhythmias with methadone - avoid. Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone and possibly disopyramide - avoid. Antibacterials: increased risk of ventricular arrhythmias with clarithromycin and moxifloxacin - avoid; avoid with rifampicin. Antidepressants: avoid with St John’s wort. Antiepileptics: avoid with carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone. Antifungals: concentration increased by ketoconazole and possibly posaconazole and voriconazole - reduce panobinostat dose; concentration possibly increased by itraconazole - avoid. Antimalarials: possibly increased risk of ventricular arrhythmias with chloroquine - avoid. Antipsychotics: avoid with pimozide. Antivirals: concentration possibly increased by ritonavir and saquinavir - reduce dose of panobinostat. Beta-blockers: possibly increased risk of ventricular arrhythmias with sotalol - avoid. Grapefruit juice: avoid concomitant use. 5HT3 antagonists: possibly increased risk of ventricular arrhythmias with granisetron and ondansetron - avoid with granisetron.

Technology Process of Panobinostat

There total 17 articles about Panobinostat which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 94.6%

(E)-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]acrylic acid methyl ester hydrochloride (441741-66-8) → panobinostat (404950-80-7)

Guidance literature:

(E)-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]acrylic acid methyl ester hydrochloride; With sodium hydroxide; In methanol; at -15 - -10 ℃; for 0.166667h;

With hydroxylamine hydrochloride; In methanol; at -15 - -10 ℃; for 3.66667h;

Reference yield: 63.0%

(E)-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]acrylic acid methyl ester (441741-65-7) → panobinostat (404950-80-7)

Guidance literature:

With hydroxylamine hydrochloride; potassium hydroxide; In methanol; at 20 ℃; for 20h;

DOI:10.1016/j.chembiol.2021.04.004

Reference yield:

(E)-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylic acid (960058-93-9) → panobinostat (404950-80-7)

Guidance literature:

(E)-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylic acid; With hydroxylamine; In methanol; water; at -15 - 25 ℃;

With hydrogenchloride; In water; pH=10.3 - 10.7;

upstream raw materials:

(E)-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]acrylic acid methyl ester hydrochloride

(E)-3-(4-(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)acrylic acid

2-methyltryptamine

phenylhydrazine

Downstream raw materials:

N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide phosphate

Refernces

• 1、 Troelsen, Kathrin S.,Calder, Ewen D. D.,Skwarska, Anna,Sneddon, Deborah,Hammond, Ester M.,Conway, Stuart J.. "Zap-Pano: a Photocaged Prodrug of the KDAC Inhibitor Panobinostat". . p. 3691 - 3700. Retrieved 2021/08/09.
• 2、 Chen, Shanwen,Zhang, Peiming,Chen, Huali,Zhang, Pu,Yu, Yu,Gan, Zongjie. "An improved and efficient synthesis of panobinostat". . p. 471 - 473. Retrieved 2018/10/15.