ISPINESIB

ID: ALA228814

Max Phase: Phase

Molecular Formula: C30H33ClN4O2

Molecular Weight: 517.07

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (1): Ispinesib
Synonyms from Alternative Forms(1):

    Canonical SMILES:  Cc1ccc(C(=O)N(CCCN)[C@@H](c2nc3cc(Cl)ccc3c(=O)n2Cc2ccccc2)C(C)C)cc1

    Standard InChI:  InChI=1S/C30H33ClN4O2/c1-20(2)27(34(17-7-16-32)29(36)23-12-10-21(3)11-13-23)28-33-26-18-24(31)14-15-25(26)30(37)35(28)19-22-8-5-4-6-9-22/h4-6,8-15,18,20,27H,7,16-17,19,32H2,1-3H3/t27-/m1/s1

    Standard InChI Key:  QJZRFPJCWMNVAV-HHHXNRCGSA-N

    Associated Targets(Human)

    A549 127892 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Centromere-associated protein E 102 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-like protein KIF1A 4 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-like protein KIF23 56 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-like protein KIF6 3 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-like protein KIFC1 51 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-like protein KIF2C 17 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Chromosome-associated kinesin KIF4A 56 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-like protein 1 1720 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    K562 73714 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HCT-116 91556 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    NCI-H1299 3248 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    BXPC-3 2997 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Liver microsomes 16955 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HERG 29587 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Plasma 7708 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cytochrome P450 1A2 26471 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cytochrome P450 2C9 32119 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cytochrome P450 2C19 29246 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cytochrome P450 2D6 33882 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cytochrome P450 3A4 53859 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    PC-3 62116 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MCF7 126967 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SK-OV-3 52876 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    DU-145 51482 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-1 heavy chain 22 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Kinesin-like protein KIFC3 20 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    LNCaP 8286 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HeLa 62764 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Sphingosine kinase 1/2 28 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Histone deacetylase 6 20808 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HepG2 196354 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    Liver 8163 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Mus musculus 284745 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SARS-CoV-2 38078 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Replicase polyprotein 1ab 11336 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Schistosoma mansoni 6170 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

    Properties

    Molecular Weight: 517.07Molecular Weight (Monoisotopic): 516.2292AlogP: 5.59#Rotatable Bonds: 9
    Polar Surface Area: 81.22Molecular Species: BASEHBA: 5HBD: 1
    #RO5 Violations: 2HBA (Lipinski): 6HBD (Lipinski): 2#RO5 Violations (Lipinski): 2
    CX Acidic pKa: CX Basic pKa: 9.77CX LogP: 5.53CX LogD: 3.25
    Aromatic Rings: 4Heavy Atoms: 37QED Weighted: 0.31Np Likeness Score: -1.15

    References

    1. Pinkerton AB, Lee TT, Hoffman TZ, Wang Y, Kahraman M, Cook TG, Severance D, Gahman TC, Noble SA, Shiau AK, Davis RL..  (2007)  Synthesis and SAR of thiophene containing kinesin spindle protein (KSP) inhibitors.,  17  (13): [PMID:17498954] [10.1016/j.bmcl.2007.04.076]
    2. Luo L, Parrish CA, Nevins N, McNulty DE, Chaudhari AM, Carson JD, Sudakin V, Shaw AN, Lehr R, Zhao H, Sweitzer S, Lad L, Wood KW, Sakowicz R, Annan RS, Huang PS, Jackson JR, Dhanak D, Copeland RA, Auger KR..  (2007)  ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism.,  (11): [PMID:17922005] [10.1038/nchembio.2007.34]
    3. Wang F, Good JA, Rath O, Kaan HY, Sutcliffe OB, Mackay SP, Kozielski F..  (2012)  Triphenylbutanamines: kinesin spindle protein inhibitors with in vivo antitumor activity.,  55  (4): [PMID:22248262] [10.1021/jm201195m]
    4. Good JA, Wang F, Rath O, Kaan HY, Talapatra SK, Podgórski D, MacKay SP, Kozielski F..  (2013)  Optimized S-trityl-L-cysteine-based inhibitors of kinesin spindle protein with potent in vivo antitumor activity in lung cancer xenograft models.,  56  (5): [PMID:23394180] [10.1021/jm3014597]
    5. Holland JP, Jones MW, Cohrs S, Schibli R, Fischer E..  (2013)  Fluorinated quinazolinones as potential radiotracers for imaging kinesin spindle protein expression.,  21  (2): [PMID:23245569] [10.1016/j.bmc.2012.11.013]
    6. Dong JJ, Li QS, Liu ZP, Wang SF, Zhao MY, Yang YH, Wang XM, Zhu HL..  (2013)  Synthesis, biological evaluation and molecular docking studies of flavone and isoflavone derivatives as a novel class of KSP (kinesin spindle protein) inhibitors.,  70  [PMID:24184776] [10.1016/j.ejmech.2013.09.042]
    7. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]
    8. Yang B, Lamb ML, Zhang T, Hennessy EJ, Grewal G, Sha L, Zambrowski M, Block MH, Dowling JE, Su N, Wu J, Deegan T, Mikule K, Wang W, Kaspera R, Chuaqui C, Chen H..  (2014)  Discovery of potent KIFC1 inhibitors using a method of integrated high-throughput synthesis and screening.,  57  (23): [PMID:25458601] [10.1021/jm501179r]
    9. Ogo N, Ishikawa Y, Sawada J, Matsuno K, Hashimoto A, Asai A..  (2015)  Structure-Guided Design of Novel l-Cysteine Derivatives as Potent KSP Inhibitors.,  (9): [PMID:26396688] [10.1021/acsmedchemlett.5b00221]
    10. Unpublished dataset, 
    11. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]
    12. Egbert M, Whitty A, Keserű GM, Vajda S..  (2019)  Why Some Targets Benefit from beyond Rule of Five Drugs.,  62  (22): [PMID:31188592] [10.1021/acs.jmedchem.8b01732]
    13. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
    14. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
    15. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]
    16. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]
    17. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]
    18. Hengst JA,Hegde S,Paulson RF,Yun JK.  (2020)  Development of SKI-349, a dual-targeted inhibitor of sphingosine kinase and microtubule polymerization.,  30  (20.0): [PMID:32736077] [10.1016/j.bmcl.2020.127453]
    19. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]
    20. Dziwornu GA, Attram HD, Gachuhi S, Chibale K..  (2020)  Chemotherapy for human schistosomiasis: how far have we come? What's new? Where do we go from here?,  11  (4.0): [PMID:33479649] [10.1039/D0MD00062K]
    21. Institute for Molecular Medicine Finland - High Throughput Biomedicine Unit.  (2023)  ECBD screening data for assay EOS300108,  [10.6019/EOS300108]