ID: ALA403664

Max Phase: Approved

First Approval: 1973

Molecular Formula: C55H84N17O21S3+

Molecular Weight: 1415.58

Molecule Type: Small molecule

Representations

Synonyms (5): Blenamax | Bleocin | Bleomycin | Bleomycin hexal | NSC-125066
Synonyms from Alternative Forms(5):

Trade Names(1): Bleo-kyowa

Canonical SMILES:  Cc1c(N)nc([C@H](CC(N)=O)NC[C@H](N)C(N)=O)nc1C(=O)N[C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@H](C(=O)NCCc1nc(-c2nc(C(=O)NCCC[S+](C)C)cs2)cs1)[C@@H](C)O)[C@@H](O[C@@H]1O[C@@H](CO)[C@@H](O)[C@H](O)[C@@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](OC(N)=O)[C@@H]1O)c1c[nH]cn1

Standard InChI:  InChI=1S/C55H83N17O21S3/c1-20-33(69-46(72-44(20)58)25(12-31(57)76)64-13-24(56)45(59)82)50(86)71-35(41(26-14-61-19-65-26)91-54-43(39(80)37(78)29(15-73)90-54)92-53-40(81)42(93-55(60)88)38(79)30(16-74)89-53)51(87)66-22(3)36(77)21(2)47(83)70-34(23(4)75)49(85)63-10-8-32-67-28(18-94-32)52-68-27(17-95-52)48(84)62-9-7-11-96(5)6/h14,17-19,21-25,29-30,34-43,53-54,64,73-75,77-81H,7-13,15-16,56H2,1-6H3,(H13-,57,58,59,60,61,62,63,65,66,69,70,71,72,76,82,83,84,85,86,87,88)/p+1/t21-,22+,23+,24-,25-,29-,30+,34-,35-,36-,37+,38+,39-,40-,41-,42-,43-,53+,54-/m0/s1

Standard InChI Key:  OYVAGSVQBOHSSS-UAPAGMARSA-O

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: Yes

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: Yes

Chirality: Yes

Availability: Yes

Prodrug: No

Properties

Molecular Weight: 1415.58

Molecular Weight (Monoisotopic): 1414.5184

AlogP:

#Rotatable Bonds:

Polar Surface Area:

Molecular Species:

HBA:

HBD:

#RO5 Violations:

HBA (Lipinski):

HBD (Lipinski):

#RO5 Violations (Lipinski):

CX Acidic pKa:

CX Basic pKa:

CX LogP:

CX LogD:

Aromatic Rings:

Heavy Atoms:

QED Weighted:

Np Likeness Score:

References

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2. Selassie CD, Hansch C, Khwaja TA..  (1990)  Structure-activity relationships of antineoplastic agents in multidrug resistance.,  33  (7): [PMID:2362268] [10.1021/jm00169a014]

3. Sidorova TA, Nigmatov AG, Kakpakova ES, Stavrovskaya AA, Gerassimova GK, Shtil AA, Serebryakov EP..  (2002)  Effects of isoprenoid analogues of SDB-ethylenediamine on multidrug resistant tumor cells alone and in combination with chemotherapeutic drugs.,  45  (24): [PMID:12431060] [10.1021/jm011010t]

4. Tabbì G, Cassino C, Cavigiolio G, Colangelo D, Ghiglia A, Viano I, Osella D..  (2002)  Water stability and cytotoxic activity relationship of a series of ferrocenium derivatives. ESR insights on the radical production during the degradation process.,  45  (26): [PMID:12477361] [10.1021/jm021003k]

5. Levin VA..  (1980)  Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability.,  23  (6): [PMID:7392035] [10.1021/jm00180a022]

6. Sengupta SK, Kogan Y, Kelly C, Szabo J..  (1988)  New actinomycin D analogues as superior chemotherapeutic agents against primary and advanced colon tumors and colon xenografts in nude mice.,  31  (4): [PMID:3351854] [10.1021/jm00399a014]

7. Ding L, Etemad-Moghadam G, Cros S, Auclair C, Meunier B..  (1991)  Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin-ellipticine" molecules having a high affinity for DNA.,  34  (3): [PMID:2002470] [10.1021/jm00107a005]

8. Sivaramakrishnan S, Gates KS..  (2008)  Possible chemical mechanisms underlying the antitumor activity of S-deoxyleinamycin.,  18  (10): [PMID:18068362] [10.1016/j.bmcl.2007.11.092]

9. Pezzuto JM, Che CT, McPherson DD, Zhu JP, Topcu G, Erdelmeier CA, Cordell GA..  (1991)  DNA as an affinity probe useful in the detection and isolation of biologically active natural products.,  54  (6): [PMID:1812211] [10.1021/np50078a006]

10. El-Sayed Ali T..  (2009)  Synthesis of some novel pyrazolo[3,4-b]pyridine and pyrazolo[3,4-d]pyrimidine derivatives bearing 5,6-diphenyl-1,2,4-triazine moiety as potential antimicrobial agents.,  44  (11): [PMID:19586688] [10.1016/j.ejmech.2009.05.031]

11. Ali Tel-S..  (2009)  Synthesis and antibacterial activity of some new thiadiaza/triazaphospholes, thiadiaza/triaza/tetrazaphosphinines and thiadiaza/tetrazaphosphepines containing 1,2,4-triazinone moiety.,  44  (11): [PMID:19615792] [10.1016/j.ejmech.2009.06.022]

12. Pränting M, Negrea A, Rhen M, Andersson DI..  (2008)  Mechanism and fitness costs of PR-39 resistance in Salmonella enterica serovar Typhimurium LT2.,  52  (8): [PMID:18519732] [10.1128/aac.00205-08]

13. Sun S, Negrea A, Rhen M, Andersson DI..  (2009)  Genetic analysis of colistin resistance in Salmonella enterica serovar Typhimurium.,  53  (6): [PMID:19332669] [10.1128/aac.01016-08]

14. 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]

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. Maiti M, Nauwelaerts K, Herdewijn P..  (2012)  Pre-microRNA binding aminoglycosides and antitumor drugs as inhibitors of Dicer catalyzed microRNA processing.,  22  (4): [PMID:22257890] [10.1016/j.bmcl.2011.12.103]

17. Manita D, Toba Y, Takakusagi Y, Matsumoto Y, Kusayanagi T, Takakusagi K, Tsukuda S, Takada K, Kanai Y, Kamisuki S, Sakaguchi K, Sugawara F..  (2011)  Camptothecin (CPT) directly binds to human heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and inhibits the hnRNP A1/topoisomerase I interaction.,  19  (24): [PMID:22071521] [10.1016/j.bmc.2011.09.059]

18. Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P..  (2012)  Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.,  20  (22): [PMID:23062825] [10.1016/j.bmc.2012.09.040]

19. El-Ashmawy MB, El-Sherbeny MA, El-Gohary NS.  (2013)  Synthesis and antitumor screening of new series of pyrimido-[4,5-b]quinolines and [1,2,4]triazolo[2,3:3,4]pyrimido[6,5-b]quinolines,  22  (6): [10.1007/s00044-012-0272-y]

20. Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute,  [10.6019/CHEMBL1201861]

21. 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]

22. Rahier NJ, Molinier N, Long C, Deshmukh SK, Kate AS, Ranadive P, Verekar SA, Jiotode M, Lavhale RR, Tokdar P, Balakrishnan A, Meignan S, Robichon C, Gomes B, Aussagues Y, Samson A, Sautel F, Bailly C..  (2015)  Anticancer activity of koningic acid and semisynthetic derivatives.,  23  (13): [PMID:25937235] [10.1016/j.bmc.2015.04.004]

23. WHO Anatomical Therapeutic Chemical Classification, 

24. British National Formulary (72nd edition), 

25. 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]

26. Crnovcic I, Gan F, Yang D, Dong LB, Schultz PG, Shen B..  (2018)  Activities of recombinant human bleomycin hydrolase on bleomycins and engineered analogues revealing new opportunities to overcome bleomycin-induced pulmonary toxicity.,  28  (16): [PMID:29730026] [10.1016/j.bmcl.2018.04.065]

27. Unpublished dataset, 

28. Brewitz L,Tumber A,Zhang X,Schofield CJ.  (2020)  Small-molecule active pharmaceutical ingredients of approved cancer therapeutics inhibit human aspartate/asparagine-β-hydroxylase.,  28  (20.0): [PMID:33069066] [10.1016/j.bmc.2020.115675]

Source

Source(5):

• Scientific Literature
• Sanger Institute Genomics of Drug Sensitivity in Cancer
• Clinical Candidates
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary