(4S,4aR,5S,6S,12aS)-4-Dimethylamino-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-naphthacene-2-carboxylic acid amide

ID: ALA1517

Max Phase: Approved

First Approval: 1964

Molecular Formula: C22H24N2O9

Molecular Weight: 460.44

Molecule Type: Small molecule

Names and Identifiers

Synonyms: 5-hydroxytetracycline dihydrate | Nitox | Oxitetracycline | Oxytetracycline | Oxytetracycline (anhydrous) | Oxytetracycline anhydrous | Oxytetracycline dehydrate | Oxytetracycline dihydrate | Oxytetracyclinum dihydras | Terrafungine | Terramycine | NSC-757262 | NSC-9169

Synonyms from Alternative Forms(8): Oxytetracycline hydrochloride | Oxytetracycline hcl | Oxytetracyclini hydrochloridum | Oxy-kesso-tetra | Terramycin | Calcium dioxytetracycline | Oxytetracycline calcium | Oxytetracycline hemicalcium

Trade Names(12): Berkmycen | Chemocycline | Galenomycin | Hi-Tet | Imperacin | Microtet | OXTC | Oxymycin | Oxytetramix-250 | Terramycin | Tetraplex | Unimycin

Canonical SMILES:  CN(C)[C@@H]1C(O)=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)cccc4[C@@](C)(O)[C@H]3[C@H](O)[C@@H]12

Standard InChI:  InChI=1S/C22H24N2O9/c1-21(32)7-5-4-6-8(25)9(7)15(26)10-12(21)17(28)13-14(24(2)3)16(27)11(20(23)31)19(30)22(13,33)18(10)29/h4-6,12-14,17,25,27-29,32-33H,1-3H3,(H2,23,31)/t12-,13-,14+,17+,21-,22+/m1/s1

Standard InChI Key:  IWVCMVBTMGNXQD-PXOLEDIWSA-N

Molfile:  

     RDKit          2D

 35 38  0  0  1  0  0  0  0  0999 V2000
    2.8000   -1.8542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5792   -1.8292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8042   -1.1542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0375   -1.8792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1917   -2.1917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5917   -1.1292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4042   -2.2167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0500   -1.1792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9500   -2.1667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9792   -0.7667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4375   -0.8167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2167   -0.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3375   -1.8042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3542   -1.1042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6500   -2.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4542   -0.0917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.3917   -2.9292    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.9375   -2.8917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2833   -2.1417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7792   -2.5667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.6417   -2.9542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.1792   -2.9042    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.6750   -0.8292    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.6250   -0.1500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.2167   -0.0667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.2667   -1.8917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.3292   -0.1500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2583   -0.7417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3000   -2.8542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8875   -1.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9125   -1.7792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8375    0.2833    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0750    0.2583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8375   -0.4417    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5750   -0.5167    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  2  5  2  0
  3  1  1  0
  4  7  1  0
  5  1  1  0
  6  2  1  0
  7  1  1  0
  8  4  2  0
  9  2  1  0
 10  6  1  0
 11  3  1  0
 12  3  1  0
 13  9  1  0
 14 13  1  0
 15  4  1  0
 11 16  1  6
 17  7  2  0
 18  9  2  0
 19 13  2  0
  1 20  1  6
 21 15  2  0
 22  5  1  0
 23  8  1  0
 10 24  1  1
 12 25  1  6
 26 15  1  0
 27 10  1  0
 28 14  2  0
 29 19  1  0
 30 31  2  0
 31 19  1  0
 32 16  1  0
 33 16  1  0
  3 34  1  6
  6 35  1  6
  6 12  1  0
  8 11  1  0
 14 10  1  0
 28 30  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1517

   OXYTETRACYCLINE

2. Alternative Forms:

   

   ALA1517

   OXYTETRACYCLINE HYDROCHLORIDE
3. 

   ALA1517

   Oxytetracycline dihydrate
4. 

   ALA1517

   Calcium dioxytetracycline

Molecule Features

Natural Product: Yes

Oral: Yes

Chemical Probe: No

Parenteral: Yes

Molecule Type: Small molecule

Topical: Yes

First In Class: No

Black Box: No

Chirality: Yes

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 460.44

Molecular Weight (Monoisotopic): 460.1482

AlogP: -1.24

#Rotatable Bonds: 2

Polar Surface Area: 201.85

Molecular Species: ACID

HBA: 10

HBD: 7

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 2.84

CX Basic pKa: 7.38

CX LogP: -4.50

CX LogD: -4.82

Aromatic Rings: 1

Heavy Atoms: 33

QED Weighted: 0.26

Np Likeness Score: 1.83

References

1. Garcia-Domenech R, de Gregorio Alapont C, de Julian-Ortiz J, Galvez J, Popa L.  (1997)  Molecular connectivity to find -blockers with low toxicity,  7  (5): [10.1016/S0960-894X(97)00046-2]

2. Moda TL, Montanari CA, Andricopulo AD..  (2007)  Hologram QSAR model for the prediction of human oral bioavailability.,  15  (24): [PMID:17870541] [10.1016/j.bmc.2007.08.060]

3. Santana L, González-Díaz H, Quezada E, Uriarte E, Yáñez M, Viña D, Orallo F..  (2008)  Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.,  51  (21): [PMID:18834112] [10.1021/jm800656v]

4. Antunes NT, Tavío MM, Mercier P, Ayling RD, Al-Momani W, Assunção P, Rosales RS, Poveda JB..  (2007)  In vitro susceptibilities of Mycoplasma putrefaciens field isolates.,  51  (9): [PMID:17638695] [10.1128/aac.00420-07]

5. Varma MV, Feng B, Obach RS, Troutman MD, Chupka J, Miller HR, El-Kattan A..  (2009)  Physicochemical determinants of human renal clearance.,  52  (15): [PMID:19445515] [10.1021/jm900403j]

6. Prado-Prado FJ, García-Mera X, González-Díaz H..  (2010)  Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.,  18  (6): [PMID:20185316] [10.1016/j.bmc.2010.01.068]

7. PubChem BioAssay data set, 

8. Obach RS, Lombardo F, Waters NJ..  (2008)  Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.,  36  (7): [PMID:18426954] [10.1124/dmd.108.020479]

9. Talevi A, Goodarzi M, Ortiz EV, Duchowicz PR, Bellera CL, Pesce G, Castro EA, Bruno-Blanch LE..  (2011)  Prediction of drug intestinal absorption by new linear and non-linear QSPR.,  46  (1): [PMID:21112128] [10.1016/j.ejmech.2010.11.005]

10. Floyd JL, Smith KP, Kumar SH, Floyd JT, Varela MF..  (2010)  LmrS is a multidrug efflux pump of the major facilitator superfamily from Staphylococcus aureus.,  54  (12): [PMID:20855745] [10.1128/aac.00580-10]

11. Fourches D, Barnes JC, Day NC, Bradley P, Reed JZ, Tropsha A..  (2010)  Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.,  23  (1): [PMID:20014752] [10.1021/tx900326k]

12. Unpublished dataset, 

13. Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program. DrugMatrix in vitro pharmacology data, 

14. Chen M, Vijay V, Shi Q, Liu Z, Fang H, Tong W..  (2011)  FDA-approved drug labeling for the study of drug-induced liver injury.,  16  (15-16): [PMID:21624500] [10.1016/j.drudis.2011.05.007]

15. Liu Z, Shi Q, Ding D, Kelly R, Fang H, Tong W..  (2011)  Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).,  7  (12): [PMID:22194678] [10.1371/journal.pcbi.1002310]

16. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H..  (2002)  Human organic anion transporters mediate the transport of tetracycline.,  88  (1): [PMID:11855680] [10.1254/jjp.88.69]

17. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

18. Singh N, Rai V, Tripathi CKM.  (2012)  Production and optimization of oxytetracycline by a new isolate Streptomyces rimosus using response surface methodology,  21  (10): [10.1007/s00044-011-9845-4]

19. Wei W, Wang H, Jiang C.  (2008)  Study of the inactivation of copper, zinc superoxide dismutase by tetracycline analogues,  17  (8): [10.1007/s00044-007-9020-0]

20. Kwon HR, Choi GJ, Choi YH, Jang KS, Sung ND, Kang MS, Moon Y, Lee SK, Kim JC..  (2010)  Suppression of pine wilt disease by an antibacterial agent, oxolinic acid.,  66  (6): [PMID:20151406] [10.1002/ps.1920]

21. NATSUME M, MATSUMOTO M, OHSHIRO A, KOZONE I, HASHIMOTO M, ABE H.  (2003)  Effect of Antibiotics on Formation of Aerial Mycelium and Production of Phytotoxins in Streptomyces spp.,  28  (2): [10.1584/jpestics.28.183]

22. 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]

23. Biour M, Ben Salem C, Chazouillères O, Grangé JD, Serfaty L, Poupon R..  (2004)  [Drug-induced liver injury; fourteenth updated edition of the bibliographic database of liver injuries and related drugs].,  28  (8-9): [PMID:15646539] [10.1016/s0399-8320(04)95062-2]

24. PubChem BioAssay data set, 

25. PubChem BioAssay data set, 

26. Tran TP, Vo DD, Di Giorgio A, Duca M..  (2015)  Ribosome-targeting antibiotics as inhibitors of oncogenic microRNAs biogenesis: Old scaffolds for new perspectives in RNA targeting.,  23  (17): [PMID:26264847] [10.1016/j.bmc.2015.07.062]

27. WHO Anatomical Therapeutic Chemical Classification, 

28. British National Formulary (72nd edition), 

29. DrugMatrix,  [10.6019/CHEMBL3885881]

30. Richter C, Helaly SE, Thongbai B, Hyde KD, Stadler M..  (2016)  Pyristriatins A and B: Pyridino-Cyathane Antibiotics from the Basidiomycete Cyathus cf. striatus.,  79  (6): [PMID:27231731] [10.1021/acs.jnatprod.6b00194]

31. Chen M, Suzuki A, Thakkar S, Yu K, Hu C, Tong W..  (2016)  DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.,  21  (4): [PMID:26948801] [10.1016/j.drudis.2016.02.015]

32. Sandargo B, Thongbai B, Stadler M, Surup F..  (2018)  Cysteine-Derived Pleurotin Congeners from the Nematode-Trapping Basidiomycete Hohenbuehelia grisea.,  81  (2): [PMID:29356520] [10.1021/acs.jnatprod.7b00713]

33. Unpublished dataset, 

34. 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]

35. Cheng T, Chepkirui C, Decock C, Matasyoh JC, Stadler M..  (2019)  Sesquiterpenes from an Eastern African Medicinal Mushroom Belonging to the Genus Sanghuangporus.,  82  (5): [PMID:31001977] [10.1021/acs.jnatprod.8b01086]

36. Messaoudi O, Sudarman E, Bendahou M, Jansen R, Stadler M, Wink J..  (2019)  Kenalactams A-E, Polyene Macrolactams Isolated from Nocardiopsis CG3.,  82  (5): [PMID:31021629] [10.1021/acs.jnatprod.8b00708]

37. Garner AL, Lorenz DA, Sandoval J, Gallagher EE, Kerk SA, Kaur T, Menon A..  (2019)  Tetracyclines as Inhibitors of Pre-microRNA Maturation: A Disconnection between RNA Binding and Inhibition.,  10  (5): [PMID:31098005] [10.1021/acsmedchemlett.9b00091]

38. 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]

39. 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]

40. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

41. Cheng T,Chepkirui C,Decock C,Matasyoh JC,Stadler M.  (2020)  Heimiomycins A-C and Calamenens from the African Basidiomycete Heimiomyces sp.,  83  (8.0): [PMID:32786884] [10.1021/acs.jnatprod.0c00486]

42. 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]

43. Paulsen MH, Engqvist M, Ausbacher D, Anderssen T, Langer MK, Haug T, Morello GR, Liikanen LE, Blencke HM, Isaksson J, Juskewitz E, Bayer A, Strøm MB..  (2021)  Amphipathic Barbiturates as Mimics of Antimicrobial Peptides and the Marine Natural Products Eusynstyelamides with Activity against Multi-resistant Clinical Isolates.,  64  (15.0): [PMID:34314189] [10.1021/acs.jmedchem.1c00734]

44. Schrey H, Scheele T, Ulonska C, Nedder DL, Neudecker T, Spiteller P, Stadler M..  (2022)  Alliacane-Type Secondary Metabolites from Submerged Cultures of the Basidiomycete Clitocybe nebularis.,  85  (10.0): [PMID:36130285] [10.1021/acs.jnatprod.2c00554]

Source

Source(12):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
• USP Dictionary of USAN and International Drug Names
• DrugMatrix
• TP-search Transporter Database
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6