Natural Product: NPC97491

Natural Product IDNPC97491
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 9-Isoobtusol
IUPAC Name (3S,4R,6R,9S,10S)-4,9-dibromo-10-chloro-5,5,9-trimethyl-1-methylidenespiro[5.5]undecan-3-ol
Synonyms 9-Isoobtusol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL522562
PubChem CID 14108771
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0002517] Chamigranes

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey JPQFUHCOKXIWBB-ZCRGAIPPSA-N
Standard InCHI InChI=1S/C15H23Br2ClO/c1-9-7-10(19)12(16)13(2,3)15(9)6-5-14(4,17)11(18)8-15/h10-12,19H,1,5-8H2,2-4H3/t10-,11-,12-,14-,15+/m0/s1
SMILES O[C@H]1CC(=C)[C@@]2(C([C@H]1Br)(C)C)CC[C@]([C@H](C2)Cl)(C)Br

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   411.98 Volume:   310.815
?
Van der Waals volume.
Dense:   1.325 LogP:   4.085
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.74
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.805
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   13.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.435 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.783 Fsp3:   0.867
MCE-18:   70.571
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.574 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.869 Promiscuous compounds:   0.084

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.752 MDCK Permeability:   -4.583
Pgp-inhibitor:   0.67 Pgp-substrate:   0.094
PAMPA:   0.813
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.0
20% Bioavailability (F20%):   0.107 30% Bioavailability (F30%):   0.022
50% Bioavailability (F50%):   0.896

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   1.0 MRP1:   0.9
Plasma Protein Binding (PPB):   93.731% Volume Distribution (VD):   0.161
Fu: 5.565%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.968 BCRP inhibitor:   0.6
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.027 CYP1A2-substrate:   0.725
CYP2C19-inhibitor:   0.448 CYP2C19-substrate:   0.806
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.58
CYP3A4-inhibitor:   0.138 CYP3A4-substrate:   0.935
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.447
HLM stability:   0.97
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  5.536 Half-life (T1/2):  1.96

ADMET: Toxicity

hERG Blockers:  0.038 hERG Blockers (10um):  0.301
Human Hepatotoxicity (H-HT):  0.234 Drug-induced Liver Injury (DILI):  0.59
AMES Toxicity:  0.808 Rat Oral Acute Toxicity:  0.844
Maximum Recommended Daily Dose:  0.76 Skin Sensitization:  0.999
Carcinogencity:  0.904 Eye Corrosion:  0.366
Eye Irritation:  0.991 Respiratory Toxicity:  0.982
Drug-induced Neurotoxicity:  0.843 Ototoxicity:  0.354
Hematotoxicity:  0.697 Drug-induced Nephrotoxicity:  0.582
Genotoxicity:  0.538 RPMI-8226 Immunitoxicity:  0.127
A549 Cytotoxicity:  0.489 Hek293 Cytotoxicity:  0.705
BCF:   2.531
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.883
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.978
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.651
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. tenerife n.a. PMID[10924166]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[16309323]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[22220686]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[24279991]
NPO7761 Laurencia majuscula Species Rhodomelaceae Eukaryota n.a. n.a. n.a. PMID[8691206]
NPO18938 Ladeania juncea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO666 Cymbidium aloifolium Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1221 Juniperus serawschanica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7761 Laurencia majuscula Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11971 Laurencia microcladia Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2491 Laurencia obtusa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5527 Ligularia atroviolacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13493 Mauremys reevesii Species Geoemydidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1054 Peucedanum graveolens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10341 Pseudogymnoascus pannorum Species Pseudeurotiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2329 Scutellaria glabra Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15600 Trifolium pannonicum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7761 Laurencia majuscula Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2491 Laurencia obtusa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7761 Laurencia majuscula Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO666 Cymbidium aloifolium Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5527 Ligularia atroviolacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10341 Pseudogymnoascus pannorum Species Pseudeurotiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2491 Laurencia obtusa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1054 Peucedanum graveolens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7761 Laurencia majuscula Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18938 Ladeania juncea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15600 Trifolium pannonicum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13493 Mauremys reevesii Species Geoemydidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2329 Scutellaria glabra Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1221 Juniperus serawschanica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11971 Laurencia microcladia Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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 Organism Name 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

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens IC50 = 10.0 ug.mL-1 PMID[10924166]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC97491 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC273356
1.0 High Similarity NPC83436
1.0 High Similarity NPC106792
1.0 High Similarity NPC607758
0.575 Remote Similarity NPC110214
0.5714 Remote Similarity NPC483534
0.5714 Remote Similarity NPC474946
0.5714 Remote Similarity NPC35397
0.5581 Remote Similarity NPC31330

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC97491 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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