ID: ALA2105763

Max Phase: Phase

Molecular Formula: C21H26N6O2

Molecular Weight: 394.48

Molecule Type: Small molecule

Representations

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

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

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 394.48

Molecular Weight (Monoisotopic): 394.2117

AlogP: 2.09

#Rotatable Bonds: 6

Polar Surface Area: 95.31

Molecular Species: BASE

HBA: 7

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 8.69

CX Basic pKa: 9.99

CX LogP: 0.69

CX LogD: -0.39

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.44

Np 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]

Source

Source(3):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names