(6S,9S,12S,14aR)-6-sec-Butyl-9-(1-methoxy-1H-indol-3-ylmethyl)-12-(6-oxo-octyl)-decahydro-4a,7,10,13-tetraaza-benzocyclododecene-5,8,11,14-tetraone

ID: ALA430060

Max Phase: Preclinical

Molecular Formula: C34H49N5O6

Molecular Weight: 623.80

Molecule Type: Protein

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Synonyms: Acipidin

Canonical SMILES: CCC(=O)CCCCC[C@@H]1NC(=O)[C@H]2CCCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2cn(OC)c3ccccc23)NC1=O

Standard InChI: InChI=1S/C34H49N5O6/c1-5-22(3)30-34(44)38-19-13-12-18-29(38)33(43)35-26(16-9-7-8-14-24(40)6-2)31(41)36-27(32(42)37-30)20-23-21-39(45-4)28-17-11-10-15-25(23)28/h10-11,15,17,21-22,26-27,29-30H,5-9,12-14,16,18-20H2,1-4H3,(H,35,43)(H,36,41)(H,37,42)/t22-,26-,27-,29+,30-/m0/s1

Standard InChI Key: JWOGUUIOCYMBPV-GMFLJSBRSA-N

Molfile:

     RDKit          2D

 47 50  0  0  0  0  0  0  0  0999 V2000
    8.9750   -0.2833    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9750   -1.1083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6870   -1.5167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3990   -1.1083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3990   -0.2833    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.6870    0.1333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3917    0.5417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1024    0.9605    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.6735    0.9478    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.1129   -1.5219    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1117   -2.3469    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.8280   -1.1104    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.5418   -1.5239    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2569   -1.1125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9708   -1.5260    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.8206    0.5544    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.5313    0.9733    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2494    0.5672    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5239    1.7983    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.2568   -0.2578    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.9919    0.9261    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.6742    0.4624    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.7038   -0.3584    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4961   -0.5885    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.4540    0.7457    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.9591    0.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7742    0.2060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.0854    0.9695    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.5752    1.6215    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7618    1.5060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5407   -2.3489    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2545   -2.7625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9696   -2.3510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.6835   -2.7646    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.3985   -2.3531    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1124   -2.7666    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.8275   -2.3552    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5413   -2.7687    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1112   -3.5916    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.0951    1.7855    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7758   -1.3646    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   16.5878   -1.5104    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8058    2.2044    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3769    2.1916    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3696    3.0166    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3917   -1.9333    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   11.1559    0.1320    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
 22 23  2  0
 10 11  2  0
  4  5  1  0
 23 24  1  0
 24 26  1  0
 25 22  1  0
 10 12  1  0
  5  6  1  0
 25 26  2  0
 12 13  1  0
 26 27  1  0
 27 28  2  0
 13 14  1  0
 28 29  1  0
  5  7  1  0
 29 30  2  0
 30 25  1  0
 14 15  2  0
 13 31  1  6
 14 20  1  0
 31 32  1  0
  1  2  1  0
 32 33  1  0
  8 16  1  0
 33 34  1  0
  7  8  1  0
 34 35  1  0
 16 17  1  0
 35 36  1  0
  1  6  1  0
 36 37  1  0
 18 17  1  0
 37 38  1  0
  7  9  2  0
 36 39  2  0
 17 19  2  0
  8 40  1  0
  2  3  1  0
 24 41  1  0
 18 20  1  0
 41 42  1  0
  4 10  1  0
 40 43  1  6
 18 21  1  6
 40 44  1  0
  4  3  1  0
 44 45  1  0
 21 22  1  0
  4 46  1  6
  8 47  1  1
M  END

Associated Targets(Human)

HDAC1 Tclin Histone deacetylase (6747 Activities)

Discover Target: HDAC1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HeLa (62764 Activities)

Natural Product: Yes	Oral: No	Chemical Probe: No	Parenteral: No
Molecule Type: Protein	Topical: No	First In Class: No	Black Box: No
Chirality: No	Availability: No	Prodrug: No

Molecular Weight: 623.80	Molecular Weight (Monoisotopic): 623.3683	AlogP: 3.07	#Rotatable Bonds: 12
Polar Surface Area: 138.84	Molecular Species: NEUTRAL	HBA: 7	HBD: 3
#RO5 Violations: 1	HBA (Lipinski): 11	HBD (Lipinski): 3	#RO5 Violations (Lipinski): 2
CX Acidic pKa: 10.83	CX Basic pKa: ┄	CX LogP: 3.37	CX LogD: 3.37
Aromatic Rings: 2	Heavy Atoms: 45	QED Weighted: 0.31	Np Likeness Score: 1.17

1. Colletti SL, Myers RW, Darkin-Rattray SJ, Gurnett AM, Dulski PM, Galuska S, Allocco JJ, Ayer MB, Li C, Lim J, Crumley TM, Cannova C, Schmatz DM, Wyvratt MJ, Fisher MH, Meinke PT.. (2001) Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 2., 11 (2): [PMID:11206439] [10.1016/s0960-894x(00)00605-3]
2. Meinke PT, Colletti SL, Doss G, Myers RW, Gurnett AM, Dulski PM, Darkin-Rattray SJ, Allocco JJ, Galuska S, Schmatz DM, Wyvratt MJ, Fisher MH.. (2000) Synthesis of apicidin-derived quinolone derivatives: parasite-selective histone deacetylase inhibitors and antiproliferative agents., 43 (25): [PMID:11124001] [10.1021/jm0001976]
3. Miller TA, Witter DJ, Belvedere S.. (2003) Histone deacetylase inhibitors., 46 (24): [PMID:14613312] [10.1021/jm0303094]
4. Murray PJ, Kranz M, Ladlow M, Taylor S, Berst F, Holmes AB, Keavey KN, Jaxa-Chamiec A, Seale PW, Stead P, Upton RJ, Croft SL, Clegg W, Elsegood MR.. (2001) The synthesis of cyclic tetrapeptoid analogues of the antiprotozoal natural product apicidin., 11 (6): [PMID:11277517] [10.1016/s0960-894x(01)00049-x]
5. Jones P, Altamura S, Chakravarty PK, Cecchetti O, De Francesco R, Gallinari P, Ingenito R, Meinke PT, Petrocchi A, Rowley M, Scarpelli R, Serafini S, Steinkühler C.. (2006) A series of novel, potent, and selective histone deacetylase inhibitors., 16 (23): [PMID:16987657] [10.1016/j.bmcl.2006.09.002]
6. Jayasuriya H, Guan Z, Dombrowski AW, Bills GF, Polishook JD, Jenkins RG, Koch L, Crumley T, Tamas T, Dubois M, Misura A, Darkin-Rattray SJ, Gregory L, Singh SB.. (2007) Isolation, structure, and coccidiostat activity of coccidiostatin A., 70 (8): [PMID:17636951] [10.1021/np0700523]
7. Jones P, Altamura S, De Francesco R, Gallinari P, Lahm A, Neddermann P, Rowley M, Serafini S, Steinkühler C.. (2008) Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases., 18 (6): [PMID:18308563] [10.1016/j.bmcl.2008.02.025]
8. Jones P, Altamura S, De Francesco R, Paz OG, Kinzel O, Mesiti G, Monteagudo E, Pescatore G, Rowley M, Verdirame M, Steinkühler C.. (2008) A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo., 51 (8): [PMID:18370373] [10.1021/jm800079s]
9. Singh EK, Ravula S, Pan CM, Pan PS, Vasko RC, Lapera SA, Weerasinghe SV, Pflum MK, McAlpine SR.. (2008) Synthesis and biological evaluation of histone deacetylase inhibitors that are based on FR235222: a cyclic tetrapeptide scaffold., 18 (8): [PMID:18381239] [10.1016/j.bmcl.2008.03.047]
10. Mazitschek R, Patel V, Wirth DF, Clardy J.. (2008) Development of a fluorescence polarization based assay for histone deacetylase ligand discovery., 18 (9): [PMID:18430569] [10.1016/j.bmcl.2008.04.007]
11. Lahm A, Paolini C, Pallaoro M, Nardi MC, Jones P, Neddermann P, Sambucini S, Bottomley MJ, Lo Surdo P, Carfí A, Koch U, De Francesco R, Steinkühler C, Gallinari P.. (2007) Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases., 104 (44): [PMID:17956988] [10.1073/pnas.0706487104]
12. Wang J, Mahmud SA, Bitterman PB, Huo Y, Slungaard A.. (2007) Histone deacetylase inhibitors suppress TF-kappaB-dependent agonist-driven tissue factor expression in endothelial cells and monocytes., 282 (39): [PMID:17675290] [10.1074/jbc.m703586200]
13. Attenni B, Ontoria JM, Cruz JC, Rowley M, Schultz-Fademrecht C, Steinkühler C, Jones P.. (2009) Histone deacetylase inhibitors with a primary amide zinc binding group display antitumor activity in xenograft model., 19 (11): [PMID:19410459] [10.1016/j.bmcl.2009.04.011]
14. Patel V, Mazitschek R, Coleman B, Nguyen C, Urgaonkar S, Cortese J, Barker RH, Greenberg E, Tang W, Bradner JE, Schreiber SL, Duraisingh MT, Wirth DF, Clardy J.. (2009) Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum., 52 (8): [PMID:19317450] [10.1021/jm801654y]
15. Pescatore G, Kinzel O, Attenni B, Cecchetti O, Fiore F, Fonsi M, Rowley M, Schultz-Fademrecht C, Serafini S, Steinkühler C, Jones P.. (2008) Optimization of a series of potent and selective ketone histone deacetylase inhibitors., 18 (20): [PMID:18809328] [10.1016/j.bmcl.2008.09.003]
16. Riester D, Hildmann C, Haus P, Galetovic A, Schober A, Schwienhorst A, Meyer-Almes FJ.. (2009) Non-isotopic dual parameter competition assay suitable for high-throughput screening of histone deacetylases., 19 (13): [PMID:19457659] [10.1016/j.bmcl.2009.04.102]
17. Hu F, Chou CJ, Gottesfeld JM.. (2009) Design and synthesis of novel hybrid benzamide-peptide histone deacetylase inhibitors., 19 (14): [PMID:19362838] [10.1016/j.bmcl.2009.03.085]
18. Olsen CA, Ghadiri MR.. (2009) Discovery of potent and selective histone deacetylase inhibitors via focused combinatorial libraries of cyclic alpha3beta-tetrapeptides., 52 (23): [PMID:19705846] [10.1021/jm900850t]
19. Estiu G, West N, Mazitschek R, Greenberg E, Bradner JE, Wiest O.. (2010) On the inhibition of histone deacetylase 8., 18 (11): [PMID:20472442] [10.1016/j.bmc.2010.03.080]
20. Bradner JE, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R.. (2010) Chemical phylogenetics of histone deacetylases., 6 (3): [PMID:20139990] [10.1038/nchembio.313]
21. Dow GS, Chen Y, Andrews KT, Caridha D, Gerena L, Gettayacamin M, Johnson J, Li Q, Melendez V, Obaldia N, Tran TN, Kozikowski AP.. (2008) Antimalarial activity of phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors., 52 (10): [PMID:18644969] [10.1128/aac.00439-08]
22. Yu D, Sakurai F, Corey DR.. (2011) Clonal Rett Syndrome cell lines to test compounds for activation of wild-type MeCP2 expression., 21 (18): [PMID:21840716] [10.1016/j.bmcl.2011.07.053]
23. PubChem BioAssay data set,
24. Hutt DM, Olsen CA, Vickers CJ, Herman D, Chalfant M, Montero A, Leman LJ, Burkle R, Maryanoff BE, Balch WE, Ghadiri MR.. (2011) Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides that Restore Trafficking and Activity of ΔF508-CFTR., 2 (9): [PMID:21984958] [10.1021/ml200136e]
25. Vickers CJ, Olsen CA, Leman LJ, Ghadiri MR.. (2012) Discovery of HDAC Inhibitors That Lack an Active Site Zn(2+)-Binding Functional Group., 3 (6): [PMID:24900500] [10.1021/ml300081u]
26. Olsen CA, Montero A, Leman LJ, Ghadiri MR.. (2012) Macrocyclic peptoid-Peptide hybrids as inhibitors of class I histone deacetylases., 3 (9): [PMID:24900543] [10.1021/ml300162r]
27. von Bargen KW, Niehaus EM, Bergander K, Brun R, Tudzynski B, Humpf HU.. (2013) Structure elucidation and antimalarial activity of apicidin F: an apicidin-like compound produced by Fusarium fujikuroi., 76 (11): [PMID:24195442] [10.1021/np4006053]
28. Mejia EJ, Loveridge ST, Stepan G, Tsai A, Jones GS, Barnes T, White KN, Drašković M, Tenney K, Tsiang M, Geleziunas R, Cihlar T, Pagratis N, Tian Y, Yu H, Crews P.. (2014) Study of marine natural products including resorcyclic acid lactones from Humicola fuscoatra that reactivate latent HIV-1 expression in an in vitro model of central memory CD4+ T cells., 77 (3): [PMID:24495105] [10.1021/np400889x]
29. Maolanon AR, Villadsen JS, Christensen NJ, Hoeck C, Friis T, Harris P, Gotfredsen CH, Fristrup P, Olsen CA.. (2014) Methyl effect in azumamides provides insight into histone deacetylase inhibition by macrocycles., 57 (22): [PMID:25380299] [10.1021/jm501399d]
30. Du L, Risinger AL, King JB, Powell DR, Cichewicz RH.. (2014) A potent HDAC inhibitor, 1-alaninechlamydocin, from a Tolypocladium sp. induces G2/M cell cycle arrest and apoptosis in MIA PaCa-2 cells., 77 (7): [PMID:24999749] [10.1021/np500387h]
31. Villadsen JS, Kitir B, Wich K, Friis T, Madsen AS, Olsen CA. (2014) An azumamide C analogue without the zinc-binding functionality, 5 (12): [10.1039/C4MD00252K]
32. Lai JI, Leman LJ, Ku S, Vickers CJ, Olsen CA, Montero A, Ghadiri MR, Gottesfeld JM.. (2017) Cyclic tetrapeptide HDAC inhibitors as potential therapeutics for spinal muscular atrophy: Screening with iPSC-derived neuronal cells., 27 (15): [PMID:28648462] [10.1016/j.bmcl.2017.06.027]
33. Hailu GS, Robaa D, Forgione M, Sippl W, Rotili D, Mai A.. (2017) Lysine Deacetylase Inhibitors in Parasites: Past, Present, and Future Perspectives., 60 (12): [PMID:28241112] [10.1021/acs.jmedchem.6b01595]
34. David E Gordon, Gwendolyn M Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Kris M White, Matthew J O'Meara, Veronica V Rezelj, Jeffrey Z Guo, Danielle L Swaney, et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing, [PMID:32353859] [10.1038/s41586-020-2286-9]
35. Lee JW, Collins JE, Wendt KL, Chakrabarti D, Cichewicz RH.. (2021) Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics., 84 (2.0): [PMID:33565879] [10.1021/acs.jnatprod.0c01370]
36. Watanabe Y, Hachiya K, Ikeda A, Nonaka K, Higo M, Muramatsu R, Noguchi C, Honsho M, Asami Y, Inahashi Y, Hirose T, Matsui H, Sunazuka T, Hanaki H, Ishii T, Teruya T, Hokari R, Ishiyama A, Iwatsuki M.. (2022) Koshidacins A and B, Antiplasmodial Cyclic Tetrapeptides from the Okinawan Fungus Pochonia boninensis FKR-0564., 85 (11.0): [PMID:36282784] [10.1021/acs.jnatprod.2c00719]

(6S,9S,12S,14aR)-6-sec-Butyl-9-(1-methoxy-1H-indol-3-ylmethyl)-12-(6-oxo-octyl)-decahydro-4a,7,10,13-tetraaza-benzocyclododecene-5,8,11,14-tetraone

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Associated Targets(non-human)

Molecule Features

Drug Indications

Mechanisms of Action

Calculated Properties

References

Source