genetecin

ID: ALA215226

Cas Number: 49863-47-0

PubChem CID: 123865

Max Phase: Preclinical

Molecular Formula: C20H40N4O10

Molecular Weight: 496.56

Molecule Type: Small molecule

Names and Identifiers

Synonyms: G418 | geneticin|G418|49863-47-0|antibiotic G 418|antibiotic G-418|G-418|G 418|A08F5XTI6G|(2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-[(1R)-1-hydroxyethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol|O-2-Amino-2,7-dideoxy-D-glycero-alpha-D-gluco-heptopyranosyl-(1-4)-O-(3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranosyl-(1-6))-D-streptamine|GET|UNII-A08F5XTI6G|BRN 1669188|CHEMBL215226|SCHEMBL5006573|DTXSID101981Show More⌵

Synonyms from Alternative Forms(1): Geneticin Sulfate Salt

Canonical SMILES:  CN[C@@H]1[C@@H](O)[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3O[C@H]([C@@H](C)O)[C@@H](O)[C@H](O)[C@H]3N)[C@@H](N)C[C@H]2N)OC[C@]1(C)O

Standard InChI:  InChI=1S/C20H40N4O10/c1-6(25)14-11(27)10(26)9(23)18(32-14)33-15-7(21)4-8(22)16(12(15)28)34-19-13(29)17(24-3)20(2,30)5-31-19/h6-19,24-30H,4-5,21-23H2,1-3H3/t6-,7+,8-,9-,10-,11+,12+,13-,14-,15-,16+,17-,18-,19-,20+/m1/s1

Standard InChI Key:  BRZYSWJRSDMWLG-DJWUNRQOSA-N

Molfile:  

     RDKit          2D

 37 39  0  0  0  0  0  0  0  0999 V2000
    6.8964   -7.1612    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.6038   -6.7458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3236   -7.1532    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3288   -7.9805    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.0346   -6.7357    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7509   -7.1454    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.4623   -6.7347    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4617   -5.9101    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.1772   -5.4953    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8933   -5.9092    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3031   -5.1930    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.8940   -6.7337    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6060   -7.1434    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.6066   -7.9721    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1784   -7.1444    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1790   -7.9731    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.7138   -5.9086    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0259   -5.9107    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7404   -5.4911    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.3117   -5.5048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6006   -5.9222    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1762   -6.7583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1680   -5.9339    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.4482   -5.5307    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7363   -5.9480    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0206   -5.5449    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.7444   -6.7725    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0369   -7.1898    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.4645   -7.1756    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4726   -8.0042    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.4399   -4.7062    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7199   -4.2990    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.1517   -4.2848    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0183   -5.1936    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.1714   -7.5748    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.0173   -5.3389    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.4623   -7.5597    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  6
  2  3  1  0
  3  4  1  1
  5  3  1  0
  5  6  1  6
  7  6  1  0
  8  7  1  0
  8  9  1  0
 10  9  1  0
 10 11  1  6
 12 10  1  0
 12 13  1  6
 13 14  1  0
 12 15  1  0
  7 15  1  0
 15 16  1  1
 10 17  1  0
  5 18  1  0
 18 19  1  1
 18 20  1  0
 21 20  1  0
  2 21  1  0
 22  1  1  0
 23 22  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  6
 27 25  1  0
 27 28  1  1
 29 27  1  0
 22 29  1  0
 29 30  1  6
 24 31  1  0
 31 32  1  0
 31 33  1  6
 24 34  1  6
 22 35  1  1
 21 36  1  1
  7 37  1  6
M  END

Alternative Forms

1. Parent:

   

   ALA215226

   GENETICIN

2. Alternative Forms:

   

   ALA215226

   GENETICIN SULFATE SALT

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 496.56

Molecular Weight (Monoisotopic): 496.2744

AlogP: -5.61

#Rotatable Bonds: 6

Polar Surface Area: 248.39

Molecular Species: BASE

HBA: 14

HBD: 10

#RO5 Violations: 2

HBA (Lipinski): 14

HBD (Lipinski): 13

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 12.39

CX Basic pKa: 9.59

CX LogP: -5.30

CX LogD: -10.24

Aromatic Rings: ┄

Heavy Atoms: 34

QED Weighted: 0.16

Np Likeness Score: 1.62

References

1. Yang G, Trylska J, Tor Y, McCammon JA..  (2006)  Binding of aminoglycosidic antibiotics to the oligonucleotide A-site model and 30S ribosomal subunit: Poisson-Boltzmann model, thermal denaturation, and fluorescence studies.,  49  (18): [PMID:16942021] [10.1021/jm060288o]

2. Yang C, Feng J, Song W, Wang J, Tsai B, Zhang Y, Scaringe WA, Hill KA, Margaritis P, High KA, Sommer SS..  (2007)  A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin.,  104  (39): [PMID:17881586] [10.1073/pnas.0610878104]

3. Bodoor K, Boyapati V, Gopu V, Boisdore M, Allam K, Miller J, Treleaven WD, Weldeghiorghis T, Aboul-ela F..  (2009)  Design and implementation of an ribonucleic acid (RNA) directed fragment library.,  52  (12): [PMID:19445516] [10.1021/jm9000659]

4. Stevens AJ, Gahan ME, Mahalingam S, Keller PA..  (2009)  The medicinal chemistry of dengue fever.,  52  (24): [PMID:19739651] [10.1021/jm900652e]

5. Nudelman I, Glikin D, Smolkin B, Hainrichson M, Belakhov V, Baasov T..  (2010)  Repairing faulty genes by aminoglycosides: development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations.,  18  (11): [PMID:20409719] [10.1016/j.bmc.2010.03.060]

6. Toth M, Frase H, Chow JW, Smith C, Vakulenko SB..  (2010)  Mutant APH(2'')-IIa enzymes with increased activity against amikacin and isepamicin.,  54  (4): [PMID:20145089] [10.1128/aac.01444-09]

7. Wang G, Inaoka T, Okamoto S, Ochi K..  (2009)  A novel insertion mutation in Streptomyces coelicolor ribosomal S12 protein results in paromomycin resistance and antibiotic overproduction.,  53  (3): [PMID:19104019] [10.1128/aac.00388-08]

8. García Liñares G, Parraud G, Labriola C, Baldessari A..  (2012)  Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana.,  20  (15): [PMID:22781310] [10.1016/j.bmc.2012.06.028]

9. De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP..  (2013)  Structure-based identification of OATP1B1/3 inhibitors.,  83  (6): [PMID:23571415] [10.1124/mol.112.084152]

10. Andrioli WJ, Conti R, Araújo MJ, Zanasi R, Cavalcanti BC, Manfrim V, Toledo JS, Tedesco D, de Moraes MO, Pessoa C, Cruz AK, Bertucci C, Sabino J, Nanayakkara DN, Pupo MT, Bastos JK..  (2014)  Mycoleptones A-C and polyketides from the endophyte Mycoleptodiscus indicus.,  77  (1): [PMID:24387625] [10.1021/np4006822]

11. Hamada K, Taguchi A, Kotake M, Aita S, Murakami S, Takayama K, Yakushiji F, Hayashi Y..  (2015)  Structure-Activity Relationship Studies of 3-epi-Deoxynegamycin Derivatives as Potent Readthrough Drug Candidates.,  6  (6): [PMID:26101575] [10.1021/acsmedchemlett.5b00121]

12. Pibiri I,Lentini L,Melfi R,Tutone M,Baldassano S,Ricco Galluzzo P,Di Leonardo A,Pace A.  (2018)  Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs.,  159  [PMID:30278331] [10.1016/j.ejmech.2018.09.057]

Source

Source(1):

• Scientific Literature