ID: ALA2021342

Max Phase: Preclinical

Molecular Formula: C19H23N7O6

Molecular Weight: 445.44

Molecule Type: Small molecule

Associated Items:

Representations

Canonical SMILES:  Nc1nc(O)c2c(n1)NCC(CNc1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1)N2

Standard InChI:  InChI=1S/C19H23N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,11-12,21,23H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t11?,12-/m0/s1

Standard InChI Key:  MSTNYGQPCMXVAQ-KIYNQFGBSA-N

Associated Targets(Human)

Folylpoly-gamma-glutamate synthetase 250 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Histone deacetylase 6 20808 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Folylpoly-gamma-glutamate synthetase 93 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Dihydrofolate reductase 1415 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

Molecule Features

Natural Product: YesOral: NoChemical Probe: NoParenteral: 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

Properties

Molecular Weight: 445.44Molecular Weight (Monoisotopic): 445.1710AlogP: 0.13#Rotatable Bonds: 9
Polar Surface Area: 211.82Molecular Species: ACIDHBA: 10HBD: 8
#RO5 Violations: 1HBA (Lipinski): 13HBD (Lipinski): 9#RO5 Violations (Lipinski): 2
CX Acidic pKa: 2.97CX Basic pKa: 3.94CX LogP: -1.66CX LogD: -6.86
Aromatic Rings: 2Heavy Atoms: 32QED Weighted: 0.26Np Likeness Score: 0.14

References

1. Taira K, Benkovic SJ..  (1988)  Evaluation of the importance of hydrophobic interactions in drug binding to dihydrofolate reductase.,  31  (1): [PMID:3275776] [10.1021/jm00396a019]
2. Li SW, Nair MG, Edwards DM, Kisliuk RL, Gaumont Y, Dev IK, Duch DS, Humphreys J, Smith GK, Ferone R..  (1991)  Folate analogues. 35. Synthesis and biological evaluation of 1-deaza, 3-deaza, and bridge-elongated analogues of N10-propargyl-5,8-dideazafolic acid.,  34  (9): [PMID:1895294] [10.1021/jm00113a011]
3. Wagner CR, Benkovic SJ..  (1992)  Probing the molecular basis of resistance to pyrimethamine by site-directed mutagenesis.,  35  (15): [PMID:1495020] [10.1021/jm00093a026]
4. Rosowsky A, Forsch RA, Moran RG..  (1989)  (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydrofolate and 6(R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-ornithine as potential antifolates and antitumor agents.,  32  (3): [PMID:2918520] [10.1021/jm00123a037]
5. Taylor EC, Harrington PJ, Fletcher SR, Beardsley GP, Moran RG..  (1985)  Synthesis of the antileukemic agents 5,10-dideazaaminopterin and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin.,  28  (7): [PMID:4009615] [10.1021/jm00145a012]
6. 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]
7. 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]
8. 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]
9. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]
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]