GALLINAMIDE A

ID: ALA541700

Max Phase: Preclinical

Molecular Formula: C31H52N4O7

Molecular Weight: 592.78

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (1): Gallinamide A
Synonyms from Alternative Forms(1):

    Canonical SMILES:  CC[C@H](C)[C@@H](C(=O)O[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)/C=C/C(=O)N1C(=O)C=C(OC)[C@@H]1C)N(C)C

    Standard InChI:  InChI=1S/C31H52N4O7/c1-12-20(6)28(34(9)10)31(40)42-25(16-19(4)5)30(39)33-23(15-18(2)3)29(38)32-21(7)13-14-26(36)35-22(8)24(41-11)17-27(35)37/h13-14,17-23,25,28H,12,15-16H2,1-11H3,(H,32,38)(H,33,39)/b14-13+/t20-,21-,22-,23-,25-,28-/m0/s1

    Standard InChI Key:  ASRBKZHDORPEHO-KYJIWOQOSA-N

    Associated Targets(Human)

    NCI-H460 60772 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cathepsin L 3852 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cathepsin H 179 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cathepsin B 3822 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cathepsin L2 273 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MDA-MB-231 73002 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MCF7 126967 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HT-29 80576 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    A-375 9258 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    PANC-1 6144 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    A549 127892 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HeLa 62764 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cathepsin S 3285 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cathepsin K 3011 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Furin 909 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Transmembrane protease serine 2 28 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    Plasmodium falciparum 966862 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Vero 26788 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Leishmania donovani 89745 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Trypanosoma cruzi 99888 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Falcipain 2 539 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    4T1 1737 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    B16-F10 4610 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cruzipain 33337 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    C2C12 756 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SARS-CoV-2 38078 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Cathepsin L1 28 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Vero C1008 1716 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Replicase polyprotein 1ab 11336 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: 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: 592.78Molecular Weight (Monoisotopic): 592.3836AlogP: 2.80#Rotatable Bonds: 16
    Polar Surface Area: 134.35Molecular Species: NEUTRALHBA: 8HBD: 2
    #RO5 Violations: 1HBA (Lipinski): 11HBD (Lipinski): 2#RO5 Violations (Lipinski): 2
    CX Acidic pKa: 9.93CX Basic pKa: 7.16CX LogP: 3.37CX LogD: 3.17
    Aromatic Rings: 0Heavy Atoms: 42QED Weighted: 0.21Np Likeness Score: 1.02

    References

    1. Linington RG, Clark BR, Trimble EE, Almanza A, Ureña LD, Kyle DE, Gerwick WH..  (2009)  Antimalarial peptides from marine cyanobacteria: isolation and structural elucidation of gallinamide A.,  72  (1): [PMID:19161344] [10.1021/np8003529]
    2. Miller B, Friedman AJ, Choi H, Hogan J, McCammon JA, Hook V, Gerwick WH..  (2014)  The marine cyanobacterial metabolite gallinamide A is a potent and selective inhibitor of human cathepsin L.,  77  (1): [PMID:24364476] [10.1021/np400727r]
    3. Conroy T, Guo JT, Elias N, Cergol KM, Gut J, Legac J, Khatoon L, Liu Y, McGowan S, Rosenthal PJ, Hunt NH, Payne RJ..  (2014)  Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials.,  57  (24): [PMID:25412465] [10.1021/jm501439w]
    4. Liu S, Gao X, Zhang L, Qin S, Wei M, Liu N, Zhao R, Li B, Meng Y, Lin G, Lu C, Liu X, Xie M, Liu T, Zhou H, Qi M, Yang G, Yang C..  (2018)  A novel Anti-Cancer Stem Cells compound optimized from the natural symplostatin 4 scaffold inhibits Wnt/β-catenin signaling pathway.,  156  [PMID:30006166] [10.1016/j.ejmech.2018.06.046]
    5. Boudreau PD, Miller BW, McCall LI, Almaliti J, Reher R, Hirata K, Le T, Siqueira-Neto JL, Hook V, Gerwick WH..  (2019)  Design of Gallinamide A Analogs as Potent Inhibitors of the Cysteine Proteases Human Cathepsin L and Trypanosoma cruzi Cruzain.,  62  (20): [PMID:31539239] [10.1021/acs.jmedchem.9b00294]
    6. Ashhurst AS, Tang AH, Fajtová P, Yoon MC, Aggarwal A, Bedding MJ, Stoye A, Beretta L, Pwee D, Drelich A, Skinner D, Li L, Meek TD, McKerrow JH, Hook V, Tseng CT, Larance M, Turville S, Gerwick WH, O'Donoghue AJ, Payne RJ..  (2022)  Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L.,  65  (4.0): [PMID:34730959] [10.1021/acs.jmedchem.1c01494]
    7. Barbosa Da Silva E, Sharma V, Hernandez-Alvarez L, Tang AH, Stoye A, O'Donoghue AJ, Gerwick WH, Payne RJ, McKerrow JH, Podust LM..  (2022)  Intramolecular Interactions Enhance the Potency of Gallinamide A Analogues against Trypanosoma cruzi.,  65  (5.0): [PMID:35188371] [10.1021/acs.jmedchem.1c02063]

    Source