(R)-N-(3-aminopropyl)-N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamide

ID: ALA228814

Chembl Id: CHEMBL228814

Max Phase: Phase

Molecular Formula: C30H33ClN4O2

Molecular Weight: 517.07

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: Ispinesib

Synonyms from Alternative Forms(5): Ispinesib mesilate | CK-0238273 | CK0238273 | SB-715992-S | Ispinesib mesylate

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

Alternative Forms

  1. Parent:

    ALA228814

    ISPINESIB
  2. Alternative Forms:

Associated Targets(Human)

A549 (127892 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CENPE Tchem Centromere-associated protein E (102 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF1A Tbio Kinesin-like protein KIF1A (4 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF23 Tbio Kinesin-like protein KIF23 (56 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF6 Tbio Kinesin-like protein KIF6 (3 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIFC1 Tchem Kinesin-like protein KIFC1 (51 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF2C Tbio Kinesin-like protein KIF2C (17 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF4A Tbio Chromosome-associated kinesin KIF4A (56 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF11 Tchem 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
KCNH2 Tclin HERG (29587 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasma (7708 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP3A4 Tclin 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
KIF5B Tbio Kinesin-1 heavy chain (22 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIFC3 Tbio 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
SPHK2 Tchem Sphingosine kinase 1/2 (28 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC6 Tclin 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
rep 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

Calculated 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]