QUISINOSTAT

ID: ALA2105763

Chembl Id: CHEMBL2105763

Cas Number: 875320-29-9

PubChem CID: 11538455

Product Number: J129670

Max Phase: Phase

Molecular Formula: C21H26N6O2

Molecular Weight: 394.48

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: Quisinostat | JNJ 26481585 | JNJ-26481585 | QUISINOSTAT|875320-29-9|JNJ-26481585|N-Hydroxy-2-(4-((((1-methyl-1H-indol-3-yl)methyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide|JNJ26481585|JNJ 26481585|9BJ85K1J8S|Quisinostat (JNJ-26481585)|N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide|5-Pyrimidinecarboxamide, N-hydroxy-2-(4-((((1-methyl-1H-indol-3-yl)methyl)amino)methyl)-1-piperidinyl)-|N-Hydroxy-2-(4-((((1-methyl-1H-indol-3-yl)methyl)aminoShow More

Synonyms from Alternative Forms(3): JNJ-26481585 | JNJ-26481585-AAC | Quisinostat hydrochloride

Canonical SMILES:  Cn1cc(CNCC2CCN(c3ncc(C(=O)NO)cn3)CC2)c2ccccc21

Standard InChI:  InChI=1S/C21H26N6O2/c1-26-14-17(18-4-2-3-5-19(18)26)11-22-10-15-6-8-27(9-7-15)21-23-12-16(13-24-21)20(28)25-29/h2-5,12-15,22,29H,6-11H2,1H3,(H,25,28)

Standard InChI Key:  PAWIYAYFNXQGAP-UHFFFAOYSA-N

Alternative Forms

  1. Parent:

    ALA2105763

    QUISINOSTAT
  2. Alternative Forms:

Associated Targets(Human)

HDAC8 Tclin Histone deacetylase 8 (4516 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC3 Tclin Histone deacetylase 3 (3654 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC2 Tclin Histone deacetylase 2 (3971 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC1 Tclin Histone deacetylase 1 (10854 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC4 Tclin Histone deacetylase 4 (2328 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC5 Tclin Histone deacetylase 5 (941 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC7 Tclin Histone deacetylase 7 (1047 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC9 Tclin Histone deacetylase 9 (708 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC6 Tclin Histone deacetylase 6 (20808 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC10 Tclin Histone deacetylase 10 (801 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC11 Tclin Histone deacetylase 11 (967 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Homo sapiens (32628 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC3 Tclin Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (735 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
LTA4H Tchem Leukotriene A4 hydrolase (1442 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HuT78 (515 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SIRT1 Tchem NAD-dependent deacetylase sirtuin 1 (3505 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SIRT2 Tchem NAD-dependent deacetylase sirtuin 2 (3979 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SIRT3 Tchem NAD-dependent deacetylase sirtuin 3 (1285 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SIRT7 Tbio NAD-dependent protein deacetylase sirtuin-7 (102 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HepG2 (196354 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HEK-293T (167025 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Daoy (570 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
D283 Med (171 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PIK3CA Tclin PI3-kinase p110-alpha subunit (12269 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PIK3CB Tchem PI3-kinase p110-beta subunit (4044 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PIK3CD Tclin PI3-kinase p110-delta subunit (6699 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Trypanosoma brucei brucei (13300 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC8 Histone deacetylase 8 (483 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium berghei (192651 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium falciparum (966862 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium yoelii (6656 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: YesAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 394.48Molecular Weight (Monoisotopic): 394.2117AlogP: 2.09#Rotatable Bonds: 6
Polar Surface Area: 95.31Molecular Species: BASEHBA: 7HBD: 3
#RO5 Violations: HBA (Lipinski): 8HBD (Lipinski): 3#RO5 Violations (Lipinski):
CX Acidic pKa: 8.69CX Basic pKa: 9.99CX LogP: 0.69CX LogD: -0.39
Aromatic Rings: 3Heavy Atoms: 29QED Weighted: 0.44Np Likeness Score: -1.24

References

1. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 
2. Carrillo AK, Guiguemde WA, Guy RK..  (2015)  Evaluation of histone deacetylase inhibitors (HDACi) as therapeutic leads for human African trypanosomiasis (HAT).,  23  (16): [PMID:25637120] [10.1016/j.bmc.2014.12.066]
3. Rabal O, Sánchez-Arias JA, Cuadrado-Tejedor M, de Miguel I, Pérez-González M, García-Barroso C, Ugarte A, Estella-Hermoso de Mendoza A, Sáez E, Espelosin M, Ursua S, Haizhong T, Wei W, Musheng X, Garcia-Osta A, Oyarzabal J..  (2016)  Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease.,  59  (19): [PMID:27606546] [10.1021/acs.jmedchem.6b00908]
4. Lu W, Yao X, Ouyang P, Dong N, Wu D, Jiang X, Wu Z, Zhang C, Xu Z, Tang Y, Zou S, Liu M, Li J, Zeng M, Lin P, Cheng F, Huang J..  (2017)  Drug Repurposing of Histone Deacetylase Inhibitors That Alleviate Neutrophilic Inflammation in Acute Lung Injury and Idiopathic Pulmonary Fibrosis via Inhibiting Leukotriene A4 Hydrolase and Blocking LTB4 Biosynthesis.,  60  (5): [PMID:28218840] [10.1021/acs.jmedchem.6b01507]
5. Marek M, Shaik TB, Heimburg T, Chakrabarti A, Lancelot J, Ramos-Morales E, Da Veiga C, Kalinin D, Melesina J, Robaa D, Schmidtkunz K, Suzuki T, Holl R, Ennifar E, Pierce RJ, Jung M, Sippl W, Romier C..  (2018)  Characterization of Histone Deacetylase 8 (HDAC8) Selective Inhibition Reveals Specific Active Site Structural and Functional Determinants.,  61  (22): [PMID:30347148] [10.1021/acs.jmedchem.8b01087]
6. Fournier JF, Bhurruth-Alcor Y, Musicki B, Aubert J, Aurelly M, Bouix-Peter C, Bouquet K, Chantalat L, Delorme M, Drean B, Duvert G, Fleury-Bregeot N, Gauthier B, Grisendi K, Harris CS, Hennequin LF, Isabet T, Joly F, Lafitte G, Millois C, Morgentin R, Pascau J, Piwnica D, Rival Y, Soulet C, Thoreau É, Tomas L..  (2018)  Squaramides as novel class I and IIB histone deacetylase inhibitors for topical treatment of cutaneous t-cell lymphoma.,  28  (17): [PMID:30122227] [10.1016/j.bmcl.2018.06.029]
7. Unpublished dataset, 
8. Shouksmith AE, Gawel JM, Nawar N, Sina D, Raouf YS, Bukhari S, He L, Johns AE, Manaswiyoungkul P, Olaoye OO, Cabral AD, Sedighi A, de Araujo ED, Gunning PT..  (2020)  Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia.,  11  (1): [PMID:31938464] [10.1021/acsmedchemlett.9b00471]
9. Géraldy M, Morgen M, Sehr P, Steimbach RR, Moi D, Ridinger J, Oehme I, Witt O, Malz M, Nogueira MS, Koch O, Gunkel N, Miller AK..  (2019)  Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated.,  62  (9): [PMID:30964290] [10.1021/acs.jmedchem.8b01936]
10. Banerjee S, Adhikari N, Amin SA, Jha T..  (2019)  Histone deacetylase 8 (HDAC8) and its inhibitors with selectivity to other isoforms: An overview.,  164  [PMID:30594678] [10.1016/j.ejmech.2018.12.039]
11. Gawel JM,Shouksmith AE,Raouf YS,Nawar N,Toutah K,Bukhari S,Manaswiyoungkul P,Olaoye OO,Israelian J,Radu TB,Cabral AD,Sina D,Sedighi A,de Araujo ED,Gunning PT.  (2020)  PTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia.,  201  [PMID:32615502] [10.1016/j.ejmech.2020.112411]
12. Ho TCS,Chan AHY,Ganesan A.  (2020)  Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight.,  63  (21.0): [PMID:32608981] [10.1021/acs.jmedchem.0c00830]
13. Rabal O, San José-Enériz E, Agirre X, Sánchez-Arias JA, de Miguel I, Ordoñez R, Garate L, Miranda E, Sáez E, Vilas-Zornoza A, Pineda-Lucena A, Estella A, Zhang F, Wu W, Xu M, Prosper F, Oyarzabal J..  (2021)  Design and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with In Vivo Efficacy in Multiple Myeloma.,  64  (6.0): [PMID:33661013] [10.1021/acs.jmedchem.0c02255]
14. Wang M, Tang T, Li R, Huang Z, Ling D, Zheng L, Ding Y, Liu T, Xu W, Zhu F, Min H, Boonhok R, Mao F, Zhu J, Li X, Jiang L, Li J..  (2022)  Drug Repurposing of Quisinostat to Discover Novel Plasmodium falciparum HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety.,  65  (5.0): [PMID:35175762] [10.1021/acs.jmedchem.1c01993]
15. Wen J, Hadden MK..  (2021)  Medulloblastoma drugs in development: Current leads, trials and drawbacks.,  215  [PMID:33636537] [10.1016/j.ejmech.2021.113268]
16. Gediya P, Parikh PK, Vyas VK, Ghate MD..  (2021)  Histone deacetylase 2: A potential therapeutic target for cancer and neurodegenerative disorders.,  216  [PMID:33714914] [10.1016/j.ejmech.2021.113332]
17. Wang Y, Tortorella M..  (2022)  Molecular design of dual inhibitors of PI3K and potential molecular target of cancer for its treatment: A review.,  228  [PMID:34894440] [10.1016/j.ejmech.2021.114039]