Structure

Physi-Chem Properties

Molecular Weight:  316.2
Volume:  350.552
LogP:  2.671
LogD:  2.751
LogS:  -3.467
# Rotatable Bonds:  7
TPSA:  38.83
# H-Bond Aceptor:  3
# H-Bond Donor:  0
# Rings:  2
# Heavy Atoms:  3

MedChem Properties

QED Drug-Likeness Score:  0.39
Synthetic Accessibility Score:  4.845
Fsp3:  0.55
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.993
MDCK Permeability:  6.31588336545974e-05
Pgp-inhibitor:  0.002
Pgp-substrate:  0.0
Human Intestinal Absorption (HIA):  0.064
20% Bioavailability (F20%):  1.0
30% Bioavailability (F30%):  1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.01
Plasma Protein Binding (PPB):  95.7770767211914%
Volume Distribution (VD):  1.696
Pgp-substrate:  2.100853681564331%

ADMET: Metabolism

CYP1A2-inhibitor:  0.075
CYP1A2-substrate:  0.789
CYP2C19-inhibitor:  0.567
CYP2C19-substrate:  0.374
CYP2C9-inhibitor:  0.39
CYP2C9-substrate:  0.944
CYP2D6-inhibitor:  0.267
CYP2D6-substrate:  0.925
CYP3A4-inhibitor:  0.9
CYP3A4-substrate:  0.208

ADMET: Excretion

Clearance (CL):  3.238
Half-life (T1/2):  0.896

ADMET: Toxicity

hERG Blockers:  0.072
Human Hepatotoxicity (H-HT):  0.143
Drug-inuced Liver Injury (DILI):  0.045
AMES Toxicity:  0.957
Rat Oral Acute Toxicity:  0.077
Maximum Recommended Daily Dose:  0.92
Skin Sensitization:  0.938
Carcinogencity:  0.877
Eye Corrosion:  0.004
Eye Irritation:  0.017
Respiratory Toxicity:  0.647

Download Data

Data Type Select
General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC478096

Natural Product ID:  NPC478096
Common Name*:   Topsentolide A2
IUPAC Name:   (2S,4Z)-2-[(E)-2-[(2R,3S)-3-[(2Z,5Z)-octa-2,5-dienyl]oxiran-2-yl]ethenyl]-3,6,7,8-tetrahydro-2H-oxonin-9-one
Synonyms:   Topsentolide A2
Standard InCHIKey:  VZWNYWSEUACDLE-VYXNFCKLSA-N
Standard InCHI:  InChI=1S/C20H28O3/c1-2-3-4-5-6-10-13-18-19(23-18)16-15-17-12-9-7-8-11-14-20(21)22-17/h3-4,6-7,9-10,15-19H,2,5,8,11-14H2,1H3/b4-3-,9-7-,10-6-,16-15+/t17-,18-,19+/m0/s1
SMILES:  CC/C=C\C/C=C\C[C@H]1[C@H](O1)/C=C/[C@@H]2C/C=C\CCCC(=O)O2
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   n.a.
PubChem CID:   11602133
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000050] Lactones

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO32840 topsentia sp. Species n.a. Eukaryota n.a. At the 20 m depth, the coast of Jeju Island, Korea 2002-OCT PMID[16643027]
NPO32840 topsentia sp. Species n.a. Eukaryota n.a. the coast of Jeju Island, Korea 2002-OCT PMID[16643027]
NPO32840 topsentia sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[17190456]
NPO32840 topsentia sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[19653640]
NPO32840 topsentia sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[2045823]
NPO32840 topsentia sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[20806907]
NPO32840 topsentia sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[8145229]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  NP Quantity Composition/Concentration

Organism ID NP ID Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  Biological Activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT81 Cell Line A549 Homo sapiens ED50 = 8.9 ug/ml PMID[16643027]
NPT146 Cell Line SK-OV-3 Homo sapiens ED50 = 11.4 ug/ml PMID[16643027]
NPT147 Cell Line SK-MEL-2 Homo sapiens ED50 = 6.5 ug/ml PMID[16643027]
NPT574 Cell Line XF498 Homo sapiens ED50 = 12.1 ug/ml PMID[16643027]
NPT148 Cell Line HCT-15 Homo sapiens ED50 = 11.4 ug/ml PMID[16643027]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC478096 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.9818 High Similarity NPC478095
0.8387 Intermediate Similarity NPC478098
0.8387 Intermediate Similarity NPC478099
0.8276 Intermediate Similarity NPC327388
0.8254 Intermediate Similarity NPC478101
0.8136 Intermediate Similarity NPC323597
0.8136 Intermediate Similarity NPC323498
0.8136 Intermediate Similarity NPC211752
0.8125 Intermediate Similarity NPC478097
0.8125 Intermediate Similarity NPC478100
0.7903 Intermediate Similarity NPC151648
0.7679 Intermediate Similarity NPC135698
0.7656 Intermediate Similarity NPC308457
0.7619 Intermediate Similarity NPC328776
0.7619 Intermediate Similarity NPC320305
0.75 Intermediate Similarity NPC474913
0.75 Intermediate Similarity NPC474774
0.746 Intermediate Similarity NPC26223
0.7429 Intermediate Similarity NPC92558
0.7424 Intermediate Similarity NPC124586
0.7424 Intermediate Similarity NPC248125
0.7385 Intermediate Similarity NPC328089
0.7385 Intermediate Similarity NPC68343
0.7368 Intermediate Similarity NPC163345
0.7321 Intermediate Similarity NPC197467
0.7313 Intermediate Similarity NPC194871
0.7313 Intermediate Similarity NPC203335
0.7302 Intermediate Similarity NPC474267
0.7302 Intermediate Similarity NPC329249
0.7302 Intermediate Similarity NPC22897
0.7302 Intermediate Similarity NPC159650
0.7231 Intermediate Similarity NPC217940
0.7222 Intermediate Similarity NPC57923
0.7206 Intermediate Similarity NPC218477
0.7206 Intermediate Similarity NPC470256
0.7188 Intermediate Similarity NPC79756
0.7143 Intermediate Similarity NPC26600
0.7143 Intermediate Similarity NPC47946
0.7121 Intermediate Similarity NPC148233
0.7121 Intermediate Similarity NPC34883
0.7121 Intermediate Similarity NPC25747
0.7101 Intermediate Similarity NPC88877
0.7101 Intermediate Similarity NPC476591
0.7101 Intermediate Similarity NPC475982
0.7077 Intermediate Similarity NPC26810
0.7077 Intermediate Similarity NPC113293
0.7049 Intermediate Similarity NPC137538
0.7031 Intermediate Similarity NPC222852
0.7031 Intermediate Similarity NPC286189
0.7031 Intermediate Similarity NPC322002
0.7027 Intermediate Similarity NPC474341
0.7015 Intermediate Similarity NPC182794
0.7 Intermediate Similarity NPC151919
0.7 Intermediate Similarity NPC106531
0.6984 Remote Similarity NPC265551
0.6984 Remote Similarity NPC323436
0.6984 Remote Similarity NPC212730
0.6984 Remote Similarity NPC471279
0.6984 Remote Similarity NPC471277
0.697 Remote Similarity NPC474658
0.697 Remote Similarity NPC68110
0.697 Remote Similarity NPC210303
0.697 Remote Similarity NPC179087
0.697 Remote Similarity NPC44343
0.6957 Remote Similarity NPC276290
0.6949 Remote Similarity NPC27264
0.6949 Remote Similarity NPC15789
0.6949 Remote Similarity NPC275316
0.6949 Remote Similarity NPC236338
0.6944 Remote Similarity NPC473489
0.6935 Remote Similarity NPC52264
0.6935 Remote Similarity NPC200845
0.6935 Remote Similarity NPC10316
0.6935 Remote Similarity NPC28779
0.6935 Remote Similarity NPC223677
0.6935 Remote Similarity NPC128061
0.6923 Remote Similarity NPC321919
0.6923 Remote Similarity NPC81896
0.6923 Remote Similarity NPC328311
0.6923 Remote Similarity NPC327112
0.6912 Remote Similarity NPC284447
0.6912 Remote Similarity NPC146811
0.6901 Remote Similarity NPC163003
0.6885 Remote Similarity NPC71761
0.6866 Remote Similarity NPC470808
0.6857 Remote Similarity NPC317583
0.6852 Remote Similarity NPC123357
0.6849 Remote Similarity NPC473582
0.6849 Remote Similarity NPC260396
0.6842 Remote Similarity NPC172042
0.6842 Remote Similarity NPC117572
0.6833 Remote Similarity NPC148056
0.6825 Remote Similarity NPC245002
0.6818 Remote Similarity NPC201939
0.6818 Remote Similarity NPC55376
0.6812 Remote Similarity NPC25298
0.6812 Remote Similarity NPC21998
0.6812 Remote Similarity NPC122627
0.6806 Remote Similarity NPC474705
0.6806 Remote Similarity NPC284006
0.678 Remote Similarity NPC207815
0.678 Remote Similarity NPC15912
0.6774 Remote Similarity NPC159535
0.6774 Remote Similarity NPC269615
0.6774 Remote Similarity NPC151761
0.6769 Remote Similarity NPC322186
0.6765 Remote Similarity NPC282760
0.6765 Remote Similarity NPC96414
0.6765 Remote Similarity NPC131174
0.6765 Remote Similarity NPC19769
0.6765 Remote Similarity NPC133904
0.6724 Remote Similarity NPC128280
0.6719 Remote Similarity NPC472445
0.6719 Remote Similarity NPC44542
0.6716 Remote Similarity NPC473737
0.6716 Remote Similarity NPC54925
0.6714 Remote Similarity NPC474823
0.6714 Remote Similarity NPC475760
0.6712 Remote Similarity NPC140287
0.6712 Remote Similarity NPC326504
0.6712 Remote Similarity NPC476355
0.6667 Remote Similarity NPC229252
0.6667 Remote Similarity NPC243532
0.6667 Remote Similarity NPC299730
0.6667 Remote Similarity NPC201356
0.6667 Remote Similarity NPC471278
0.6667 Remote Similarity NPC19241
0.6667 Remote Similarity NPC477084
0.6667 Remote Similarity NPC475936
0.6667 Remote Similarity NPC186531
0.6667 Remote Similarity NPC84038
0.6667 Remote Similarity NPC293114
0.6667 Remote Similarity NPC143857
0.6622 Remote Similarity NPC473948
0.662 Remote Similarity NPC130618
0.662 Remote Similarity NPC151481
0.662 Remote Similarity NPC269841
0.662 Remote Similarity NPC475004
0.6618 Remote Similarity NPC470320
0.6618 Remote Similarity NPC475221
0.6615 Remote Similarity NPC254095
0.6613 Remote Similarity NPC477780
0.6613 Remote Similarity NPC39633
0.6613 Remote Similarity NPC139545
0.6613 Remote Similarity NPC309606
0.6613 Remote Similarity NPC477781
0.661 Remote Similarity NPC91495
0.6607 Remote Similarity NPC187922
0.6582 Remote Similarity NPC53867
0.6582 Remote Similarity NPC475842
0.6579 Remote Similarity NPC318481
0.6579 Remote Similarity NPC253749
0.6579 Remote Similarity NPC267231
0.6579 Remote Similarity NPC182292
0.6575 Remote Similarity NPC269206
0.6575 Remote Similarity NPC135703
0.6575 Remote Similarity NPC287878
0.6575 Remote Similarity NPC295633
0.6575 Remote Similarity NPC58956
0.6571 Remote Similarity NPC225272
0.6571 Remote Similarity NPC26500
0.6571 Remote Similarity NPC49863
0.6571 Remote Similarity NPC99619
0.6567 Remote Similarity NPC271282
0.6567 Remote Similarity NPC66460
0.6567 Remote Similarity NPC321838
0.6567 Remote Similarity NPC325929
0.6562 Remote Similarity NPC252860
0.6552 Remote Similarity NPC270706
0.6538 Remote Similarity NPC141810
0.6538 Remote Similarity NPC475481
0.6538 Remote Similarity NPC79277
0.6533 Remote Similarity NPC123360
0.6533 Remote Similarity NPC188860
0.6528 Remote Similarity NPC202011
0.6528 Remote Similarity NPC476037
0.6528 Remote Similarity NPC469660
0.6528 Remote Similarity NPC323677
0.6528 Remote Similarity NPC477429
0.6528 Remote Similarity NPC476012
0.6528 Remote Similarity NPC475310
0.6522 Remote Similarity NPC470688
0.6522 Remote Similarity NPC326268
0.6522 Remote Similarity NPC476655
0.6522 Remote Similarity NPC136164
0.6522 Remote Similarity NPC318420
0.6522 Remote Similarity NPC323045
0.6522 Remote Similarity NPC476654
0.6522 Remote Similarity NPC471565
0.6522 Remote Similarity NPC255863
0.6522 Remote Similarity NPC245947
0.6522 Remote Similarity NPC320642
0.6522 Remote Similarity NPC323477
0.6522 Remote Similarity NPC471566
0.6522 Remote Similarity NPC317881
0.6522 Remote Similarity NPC476657
0.6515 Remote Similarity NPC82465
0.6515 Remote Similarity NPC97570
0.6515 Remote Similarity NPC318306
0.6515 Remote Similarity NPC133600

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC478096 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.7818 Intermediate Similarity NPD5343 Approved
0.7719 Intermediate Similarity NPD6927 Phase 3
0.7273 Intermediate Similarity NPD6097 Approved
0.7273 Intermediate Similarity NPD6096 Approved
0.7015 Intermediate Similarity NPD2685 Clinical (unspecified phase)
0.6923 Remote Similarity NPD4246 Clinical (unspecified phase)
0.6875 Remote Similarity NPD6109 Phase 1
0.6842 Remote Similarity NPD4222 Approved
0.6842 Remote Similarity NPD3174 Discontinued
0.6571 Remote Similarity NPD4247 Clinical (unspecified phase)
0.65 Remote Similarity NPD3173 Approved
0.6364 Remote Similarity NPD585 Clinical (unspecified phase)
0.629 Remote Similarity NPD29 Approved
0.629 Remote Similarity NPD28 Approved
0.6271 Remote Similarity NPD39 Approved
0.625 Remote Similarity NPD5209 Approved
0.6207 Remote Similarity NPD5326 Phase 3
0.6184 Remote Similarity NPD8039 Approved
0.6143 Remote Similarity NPD3197 Phase 1
0.6094 Remote Similarity NPD3172 Approved
0.6 Remote Similarity NPD3194 Approved
0.6 Remote Similarity NPD4266 Approved
0.6 Remote Similarity NPD5790 Clinical (unspecified phase)
0.6 Remote Similarity NPD3196 Approved
0.6 Remote Similarity NPD3195 Phase 2
0.5915 Remote Similarity NPD5325 Clinical (unspecified phase)
0.5862 Remote Similarity NPD46 Approved
0.5862 Remote Similarity NPD6698 Approved
0.5833 Remote Similarity NPD1733 Clinical (unspecified phase)
0.5783 Remote Similarity NPD7154 Phase 3
0.5769 Remote Similarity NPD1452 Discontinued
0.575 Remote Similarity NPD4268 Approved
0.575 Remote Similarity NPD4271 Approved
0.5714 Remote Similarity NPD4220 Pre-registration
0.5682 Remote Similarity NPD7838 Discovery
0.561 Remote Similarity NPD4252 Approved
0.561 Remote Similarity NPD4821 Approved
0.561 Remote Similarity NPD4822 Approved
0.561 Remote Similarity NPD4820 Approved
0.561 Remote Similarity NPD4819 Approved

  Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data