Natural Product: NPC475704

Natural Product IDNPC475704
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Alpha-Santalol
IUPAC Name (Z)-5-[(1R,3R,6S)-2,3-dimethyl-4,5,6,7-tetrahydro-1H-tricyclo[2.2.1.0^{2,6}]heptan-3-yl]-2-methylpent-2-en-1-ol
Synonyms (Z)-Alpha-Santalol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL512210
PubChem CID 11085337
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 PDEQKAVEYSOLJX-RQGDDBKYSA-N
Standard InCHI InChI=1S/C15H24O/c1-10(9-16)5-4-6-14(2)11-7-12-13(8-11)15(12,14)3/h5,11-13,16H,4,6-9H2,1-3H3/b10-5-/t11?,12-,13+,14-,15?/m1/s1
SMILES OC/C(=CCC[C@]1(C)C2C[C@@H]3C1(C)[C@@H]3C2)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   220.18 Volume:   248.481
?
Van der Waals volume.
Dense:   0.886 LogP:   3.65
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.6
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.737
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   10.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.72 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.597 Fsp3:   0.867
MCE-18:   47.5
?
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:   0.109 Fluc inhibitor:   0.019
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
?
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:   0.723 Promiscuous compounds:   0.411

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.551 MDCK Permeability:   -4.663
Pgp-inhibitor:   0.772 Pgp-substrate:   0.152
PAMPA:   0.017
?
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):   0.05
20% Bioavailability (F20%):   0.772 30% Bioavailability (F30%):   0.526
50% Bioavailability (F50%):   0.84

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.964 MRP1:   0.991
Plasma Protein Binding (PPB):   75.326% Volume Distribution (VD):   0.078
Fu: 27.072%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.051
OATP1B3 inhibitor:   0.045 BCRP inhibitor:   0.396
BSEP inhibitor:   0.967

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.48 CYP2C19-substrate:   0.059
CYP2C9-inhibitor:   0.835 CYP2C9-substrate:   0.035
CYP2D6-inhibitor:   0.016 CYP2D6-substrate:   0.183
CYP3A4-inhibitor:   0.969 CYP3A4-substrate:   0.542
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.935
HLM stability:   0.08
?
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):  9.876 Half-life (T1/2):  0.748

ADMET: Toxicity

hERG Blockers:  0.192 hERG Blockers (10um):  0.447
Human Hepatotoxicity (H-HT):  0.664 Drug-induced Liver Injury (DILI):  0.031
AMES Toxicity:  0.382 Rat Oral Acute Toxicity:  0.086
Maximum Recommended Daily Dose:  0.267 Skin Sensitization:  0.831
Carcinogencity:  0.452 Eye Corrosion:  0.135
Eye Irritation:  0.873 Respiratory Toxicity:  0.848
Drug-induced Neurotoxicity:  0.366 Ototoxicity:  0.512
Hematotoxicity:  0.375 Drug-induced Nephrotoxicity:  0.195
Genotoxicity:  0.018 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.053 Hek293 Cytotoxicity:  0.192
BCF:   1.987
?
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:   4.045
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.216
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.701
?
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
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. PMID[15974602]
NPO52048 Inula viscosa Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[30874370]
NPO59923 Myriactis nepalensis Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[35889501]
NPO52048 Inula viscosa Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38245842]
NPO52307 psychotria asiatica Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[38613430]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52048 Inula viscosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17691 Santalum album Species Santalaceae 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
NPO52048 Inula viscosa Oil n.a. 1.4 n.a. n.a. % PMID[30874370]
NPO52048 Inula viscosa Oil n.a. 0.6 n.a. n.a. % PMID[30874370]
NPO52307 psychotria asiatica Oil n.a. 0.4 n.a. n.a. % PMID[38613430]
NPO59923 Myriactis nepalensis Oil n.a. 3.6 n.a. n.a. % PMID[35889501]

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
NPT3014 Protein family Tubulin Sus scrofa FC = 7000.0 n.a. PMID[17060533]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT3013 Cell line HN5 Homo sapiens TGI = 8200.0 nM PMID[24063567]
NPT3013 Cell line HN5 Homo sapiens GI50 = 5300.0 nM PMID[18474583]
NPT451 Organism Helicobacter pylori Helicobacter pylori IZ = 21.6 mm PMID[7807120]
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC = 15.6 ug.mL-1 PMID[22472691]
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC = 7.8 ug.mL-1 PMID[22472691]
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC = 31.3 ug.mL-1 PubChem BioAssay data set
NPT452 Organism Helicobacter pylori SS1 Helicobacter pylori SS1 IZ = 11.5 mm PMID[2746258]
NPT452 Organism Helicobacter pylori SS1 Helicobacter pylori SS1 MIC = 31.3 ug.mL-1 PMID[23398362]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 9200.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 6000.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 5300.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 5400.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 7600.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 7700.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 4600.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 3500.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 3400.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 3900.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 5500.0 nM PMID[25993496]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 4500.0 nM PMID[25993496]

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
- Rattus norvegicus LD50 = 3800.0 mg/kg ToxVal
- Oryctolagus cuniculus LD50 > 5000.0 mg/kg ToxVal

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 NPC475704 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
0.8621 High Similarity NPC135650
0.5833 Remote Similarity NPC14352
0.5833 Remote Similarity NPC234527
0.5263 Remote Similarity NPC309178
0.5263 Remote Similarity NPC234264
0.5263 Remote Similarity NPC47840

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC475704 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