Natural Product: NPC306195

Natural Product IDNPC306195
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bisabolol
IUPAC Name (2S)-6-methyl-2-(4-methylcyclohex-3-en-1-yl)hept-5-en-2-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1561544
PubChem CID 6097621
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids

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 RGZSQWQPBWRIAQ-LOACHALJSA-N
Standard InCHI InChI=1S/C15H26O/c1-12(2)6-5-11-15(4,16)14-9-7-13(3)8-10-14/h6-7,14,16H,5,8-11H2,1-4H3/t14?,15-/m0/s1
SMILES CC(=CCC[C@@](C)(C1CC=C(C)CC1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   222.2 Volume:   262.957
?
Van der Waals volume.
Dense:   0.845 LogP:   4.107
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.31
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.537
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   7.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.706 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.673 Fsp3:   0.733
MCE-18:   20.769
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.261 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.993 Promiscuous compounds:   0.259

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.511 MDCK Permeability:   -4.719
Pgp-inhibitor:   0.732 Pgp-substrate:   0.085
PAMPA:   0.338
?
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):   0.055
20% Bioavailability (F20%):   0.444 30% Bioavailability (F30%):   0.517
50% Bioavailability (F50%):   0.909

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.093 MRP1:   0.886
Plasma Protein Binding (PPB):   73.489% Volume Distribution (VD):   -0.036
Fu: 23.769%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.887 BCRP inhibitor:   0.351
BSEP inhibitor:   0.841

ADMET: Metabolism

CYP1A2-inhibitor:   0.219 CYP1A2-substrate:   0.896
CYP2C19-inhibitor:   0.954 CYP2C19-substrate:   0.018
CYP2C9-inhibitor:   0.274 CYP2C9-substrate:   0.015
CYP2D6-inhibitor:   0.223 CYP2D6-substrate:   0.069
CYP3A4-inhibitor:   0.029 CYP3A4-substrate:   0.772
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.716
HLM stability:   0.911
?
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):  12.345 Half-life (T1/2):  1.587

ADMET: Toxicity

hERG Blockers:  0.054 hERG Blockers (10um):  0.3
Human Hepatotoxicity (H-HT):  0.524 Drug-induced Liver Injury (DILI):  0.078
AMES Toxicity:  0.17 Rat Oral Acute Toxicity:  0.193
Maximum Recommended Daily Dose:  0.292 Skin Sensitization:  0.95
Carcinogencity:  0.564 Eye Corrosion:  0.821
Eye Irritation:  0.978 Respiratory Toxicity:  0.53
Drug-induced Neurotoxicity:  0.556 Ototoxicity:  0.206
Hematotoxicity:  0.134 Drug-induced Nephrotoxicity:  0.287
Genotoxicity:  0.012 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.233 Hek293 Cytotoxicity:  0.094
BCF:   2.236
?
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:   4.354
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.551
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.176
?
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
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[16562834]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. leaf n.a. PMID[17125224]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. bark n.a. PMID[21875098]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. fruit n.a. PMID[24155209]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[24868863]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[24959987]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[25089845]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[25302569]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota Buds n.a. n.a. PMID[25927817]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota leaves n.a. n.a. PMID[27400231]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota Twigs n.a. n.a. PMID[28682072]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota Twigs n.a. n.a. PMID[29883114]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota Aerial Parts n.a. n.a. PMID[32991171]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[38612781]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18046 Mosla chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9546 Cinamomum cassia n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO355 Peperomia sui Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO355 Peperomia sui Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18046 Mosla chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO355 Peperomia sui Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18046 Mosla chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18046 Mosla chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8255 Cinnamomum aromaticum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9546 Cinamomum cassia n.a. n.a. n.a. n.a. n.a. n.a. Database[TM-MC]
NPO18046 Mosla chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24267 Paeonia veitchii Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21355 Elsholtzia ciliata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18046 Mosla chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21410 Populus balsamifera Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8255 Cinnamomum aromaticum Species Lauraceae 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
NPT282 Individual protein MAP kinase ERK2 Homo sapiens Potency = 5011.9 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT792 Individual protein Arachidonate 15-lipoxygenase Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 562.3 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 601.2 nM PubChem BioAssay data set

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 NPC306195 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 NPC35519
1.0 High Similarity NPC179169
1.0 High Similarity NPC157781
1.0 High Similarity NPC181255
0.6471 Remote Similarity NPC471200
0.6207 Remote Similarity NPC26906
0.6207 Remote Similarity NPC214584
0.5588 Remote Similarity NPC329773
0.5455 Remote Similarity NPC63111

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC306195 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