1-isopropyl-6-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide

ID: ALA3414619

Chembl Id: CHEMBL3414619

Max Phase: Preclinical

Molecular Formula: C33H43N7O2

Molecular Weight: 569.75

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Canonical SMILES:  CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccc(N3CCN(C(C)C)CC3)nc2)cc2c1cnn2C(C)C

Standard InChI:  InChI=1S/C33H43N7O2/c1-7-8-24-15-23(6)37-33(42)28(24)19-35-32(41)27-16-26(17-30-29(27)20-36-40(30)22(4)5)25-9-10-31(34-18-25)39-13-11-38(12-14-39)21(2)3/h9-10,15-18,20-22H,7-8,11-14,19H2,1-6H3,(H,35,41)(H,37,42)

Standard InChI Key:  DPJNKUOXBZSZAI-UHFFFAOYSA-N

Alternative Forms

  1. Parent:

    ALA3414619

    ---

Associated Targets(Human)

EZH2 Tclin Histone-lysine N-methyltransferase EZH2 (2012 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EZH1 Tchem Histone-lysine N-methyltransferase EZH1 (112 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
U2OS (164939 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Fibroblast (163371 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HEK-293T (167025 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC6 Tclin Histone deacetylase 6 (20808 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ABL1 Tclin Tyrosine-protein kinase ABL (18331 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
AURKA Tchem Serine/threonine-protein kinase Aurora-A (10240 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BRD4 Tchem Bromodomain-containing protein 4 (13122 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BRPF1 Tchem Peregrin (2217 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CDK2 Tchem Cyclin-dependent kinase 2 (9050 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CSNK1D Tchem Casein kinase I delta (4546 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FGFR3 Tclin Fibroblast growth factor receptor 3 (7811 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GSK3B Tclin Glycogen synthase kinase-3 beta (11785 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MAPK1 Tchem MAP kinase ERK2 (25055 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TRIM24 Tchem Transcription intermediary factor 1-alpha (2087 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MDA-MB-231 (73002 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MDA-MB-468 (9477 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HRH3 Tclin Histamine H3 receptor (10389 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLC6A2 Tclin Norepinephrine transporter (10102 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SIGMAR1 Tclin Sigma opioid receptor (6358 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TMEM97 Tchem Sigma intracellular receptor 2 (973 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PRMT3 Tchem Protein arginine N-methyltransferase 3 (219 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CAMK4 Tbio CaM kinase IV (2116 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MCF-10A (2462 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HepG2 (196354 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

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

Molecule Features

Natural Product: NoOral: NoChemical Probe: YesParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: 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: 569.75Molecular Weight (Monoisotopic): 569.3478AlogP: 5.09#Rotatable Bonds: 9
Polar Surface Area: 99.15Molecular Species: NEUTRALHBA: 7HBD: 2
#RO5 Violations: 2HBA (Lipinski): 9HBD (Lipinski): 2#RO5 Violations (Lipinski): 2
CX Acidic pKa: 11.63CX Basic pKa: 8.06CX LogP: 4.01CX LogD: 3.26
Aromatic Rings: 4Heavy Atoms: 42QED Weighted: 0.29Np Likeness Score: -1.57

References

1. Kaniskan HÜ, Konze KD, Jin J..  (2015)  Selective inhibitors of protein methyltransferases.,  58  (4): [PMID:25406853] [10.1021/jm501234a]
2. 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]
3. Yang X, Li F, Konze KD, Meslamani J, Ma A, Brown PJ, Zhou MM, Arrowsmith CH, Kaniskan HÜ, Vedadi M, Jin J..  (2016)  Structure-Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors.,  59  (16): [PMID:27468126] [10.1021/acs.jmedchem.6b00855]
4. 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]
5. 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]
6. 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]
7. 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]
8.  (2021)  EUbOPEN Chemogenomics Library wave 1,  [10.6019/CHEMBL4689842]
9. Martin MC,Zeng G,Yu J,Schiltz GE.  (2020)  Small Molecule Approaches for Targeting the Polycomb Repressive Complex 2 (PRC2) in Cancer.,  63  (24.0): [PMID:33283516] [10.1021/acs.jmedchem.0c01344]
10. 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]
11. EUbOPEN.  (2022)  EUbOPEN Chemogenomics Library wave 2 - DSF,  [10.6019/CHEMBL5060014]
12. Wang C, Chen X, Liu X, Lu D, Li S, Qu L, Yin F, Luo H, Zhang Y, Luo Z, Cui N, Kong L, Wang X..  (2022)  Discovery of precision targeting EZH2 degraders for triple-negative breast cancer.,  238  [PMID:35623249] [10.1016/j.ejmech.2022.114462]
13. Talukdar A, Mukherjee A, Bhattacharya D..  (2022)  Fascinating Transformation of SAM-Competitive Protein Methyltransferase Inhibitors from Nucleoside Analogues to Non-Nucleoside Analogues.,  65  (3.0): [PMID:35014841] [10.1021/acs.jmedchem.1c01208]
14. EUbOPEN.  (2023)  Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5209897]
15. EUbOPEN.  (2023)  Affinity Biochemical Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5210307]
16. EUbOPEN.  (2023)  Selectivity Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5212743]
17. Li Y, Yang G, Yang C, Tang P, Chen J, Zhang J, Liu J, Ouyang L..  (2021)  Targeting Autophagy-Related Epigenetic Regulators for Cancer Drug Discovery.,  64  (16.0): [PMID:34378389] [10.1021/acs.jmedchem.1c00579]
18. Institute for Molecular Medicine Finland - High Throughput Biomedicine Unit.  (2023)  ECBD screening data for assay EOS300108,  [10.6019/EOS300108]