Natural Product: NPC268160

Natural Product IDNPC268160
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 19-Hydroxytotarol
IUPAC Name (4bS,8S,8aR)-8-(hydroxymethyl)-4b,8-dimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-ol
Synonyms 19-Hydroxy-Totarol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL478771
PubChem CID 15694357
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids

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 NFEAIVZJRVEKFD-DFQSSKMNSA-N
Standard InCHI InChI=1S/C20H30O2/c1-13(2)18-14-6-9-17-19(3,12-21)10-5-11-20(17,4)15(14)7-8-16(18)22/h7-8,13,17,21-22H,5-6,9-12H2,1-4H3/t17-,19+,20+/m0/s1
SMILES CC(C)c1c2CC[C@H]3[C@](C)(CCC[C@]3(C)c2ccc1O)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.22 Volume:   338.478
?
Van der Waals volume.
Dense:   0.893 LogP:   3.247
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.111
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.025
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   16.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.843 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.759 Fsp3:   0.7
MCE-18:   72.882
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.07 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.163
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.01
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.307 Promiscuous compounds:   0.02

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.627 MDCK Permeability:   -4.798
Pgp-inhibitor:   0.064 Pgp-substrate:   0.163
PAMPA:   0.443
?
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):   0.005
20% Bioavailability (F20%):   0.784 30% Bioavailability (F30%):   0.866
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.248 MRP1:   0.847
Plasma Protein Binding (PPB):   90.147% Volume Distribution (VD):   0.438
Fu: 12.823%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.194
OATP1B3 inhibitor:   0.311 BCRP inhibitor:   0.537
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.982 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.994 CYP2C9-substrate:   0.051
CYP2D6-inhibitor:   0.956 CYP2D6-substrate:   0.342
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.748
CYP2B6-substrate:   0.494 CYP2C8-inhibitor:   0.828
HLM stability:   0.772
?
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):  5.992 Half-life (T1/2):  0.73

ADMET: Toxicity

hERG Blockers:  0.1 hERG Blockers (10um):  0.442
Human Hepatotoxicity (H-HT):  0.772 Drug-induced Liver Injury (DILI):  0.056
AMES Toxicity:  0.388 Rat Oral Acute Toxicity:  0.251
Maximum Recommended Daily Dose:  0.582 Skin Sensitization:  0.96
Carcinogencity:  0.851 Eye Corrosion:  0.011
Eye Irritation:  0.917 Respiratory Toxicity:  0.85
Drug-induced Neurotoxicity:  0.048 Ototoxicity:  0.771
Hematotoxicity:  0.414 Drug-induced Nephrotoxicity:  0.723
Genotoxicity:  0.034 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.252 Hek293 Cytotoxicity:  0.55
BCF:   2.14
?
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:   4.495
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.917
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.25
?
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
NPO9389 Swertia bimaculata Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/cbdv.200490123]
NPO9389 Swertia bimaculata Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)98635-7]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[10869194]
NPO6506 Cupaniopsis macropetala Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[18163587]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota leaves n.a. n.a. PMID[18588343]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[19331340]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27700077]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[28225280]
NPO9921 Peyronellaea glomerata Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[29738260]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31789520]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31804070]
NPO1849 Pleiospermium alatum Species Rutaceae Eukaryota n.a. root n.a. Database[Article]
NPO1849 Pleiospermium alatum Species Rutaceae Eukaryota n.a. stem n.a. Database[Article]
NPO1849 Pleiospermium alatum Species Rutaceae Eukaryota n.a. leaf n.a. Database[Article]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2771 Teucrium ramosissimum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14265 Stokesia laevis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22 Osmitopsis asteriscoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9389 Swertia bimaculata Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15989 Rabdosia yuennanensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14606 Leucanthemella serotina Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9921 Peyronellaea glomerata Species Didymellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15989 Rabdosia yuennanensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2771 Teucrium ramosissimum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14755 Ornithogalum montanum Species Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1849 Pleiospermium alatum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25110 Neomirandea angularis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15989 Rabdosia yuennanensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9389 Swertia bimaculata Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6506 Cupaniopsis macropetala Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9921 Peyronellaea glomerata Species Didymellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4452 Erythrina falcata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14606 Leucanthemella serotina Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14265 Stokesia laevis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15179 Cocculus hirsutus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO930 Psalliota campestris n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO22 Osmitopsis asteriscoides Species Asteraceae 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
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 15.89 % PMID[23571415]
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 20.52 % PMID[23571415]

In vitro activity

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

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 NPC268160 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
0.78 Intermediate Similarity NPC141782
0.7358 Intermediate Similarity NPC253627
0.6786 Remote Similarity NPC198014
0.6545 Remote Similarity NPC192948
0.6545 Remote Similarity NPC147179
0.6545 Remote Similarity NPC35797
0.6545 Remote Similarity NPC606176
0.6545 Remote Similarity NPC606869
0.625 Remote Similarity NPC600120
0.625 Remote Similarity NPC604782
0.6182 Remote Similarity NPC220596
0.5738 Remote Similarity NPC71610
0.5714 Remote Similarity NPC483489
0.5614 Remote Similarity NPC19856
0.5517 Remote Similarity NPC604866
0.5323 Remote Similarity NPC603947
0.5254 Remote Similarity NPC308828
0.5161 Remote Similarity NPC605657

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC268160 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