NPASS Compound

Natural Product: NPC196479

Natural Product ID	NPC196479
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Obliquol B
IUPAC Name	4-[(E)-tetradec-4-enyl]benzene-1,2-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL457469
PubChem CID	25113692
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0001286] Benzenediols [CHEMONTID:0000135] Catechols

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

Chemical Representations

RDKit 3D 54 54 0 0 0 0 0 0 0 0999 V2000 3.7265 1.8075 1.2454 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1529 1.7115 1.6421 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0940 1.1275 0.6495 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9082 -0.2901 0.2583 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5879 -0.5698 -0.3569 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5064 -2.0532 -0.7983 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1746 -2.2696 -1.4131 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9925 -2.0029 -0.5116 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7569 -2.2976 -1.3394 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4936 -2.0836 -0.5961 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4092 -1.2069 -0.9937 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6895 -0.9852 -0.2362 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8133 -1.3097 -1.1670 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1507 -1.1200 -0.4897 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2609 0.2934 -0.0675 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8599 0.7684 1.1638 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9856 2.0929 1.5037 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5257 3.0003 0.6074 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9376 2.5602 -0.6337 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7992 1.2440 -0.9381 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4774 3.4854 -1.5206 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6628 4.3313 0.9222 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5758 1.7920 0.1527 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3345 2.8562 1.5209 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0366 1.1565 1.8236 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2662 1.2156 2.6541 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5354 2.7579 1.8478 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1683 1.2815 0.9875 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0616 1.7274 -0.3121 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7230 -0.5248 -0.4895 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1364 -1.0058 1.0950 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4297 0.0457 -1.2498 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7754 -0.4893 0.4019 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2664 -2.1377 -1.6017 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7328 -2.6790 0.0656 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1365 -3.3326 -1.7744 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0919 -1.5812 -2.2926 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9373 -0.8944 -0.2957 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0317 -2.5414 0.4336 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8330 -1.7333 -2.2679 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8048 -3.3895 -1.5927 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6550 -2.6708 0.3041 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1900 -0.6528 -1.8981 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7578 -1.6769 0.6278 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7496 0.0379 0.1604 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7262 -0.6076 -2.0425 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7302 -2.3339 -1.5707 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1721 -1.7300 0.4427 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9539 -1.4173 -1.1932 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4324 0.0566 1.8763 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6762 2.4690 2.4584 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1174 0.8855 -1.9060 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0668 4.2494 -1.2518 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4841 4.6332 1.4159 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 18 22 1 0 20 15 1 0 1 23 1 0 1 24 1 0 1 25 1 0 2 26 1 0 2 27 1 0 3 28 1 0 3 29 1 0 4 30 1 0 4 31 1 0 5 32 1 0 5 33 1 0 6 34 1 0 6 35 1 0 7 36 1 0 7 37 1 0 8 38 1 0 8 39 1 0 9 40 1 0 9 41 1 0 10 42 1 0 11 43 1 0 12 44 1 0 12 45 1 0 13 46 1 0 13 47 1 0 14 48 1 0 14 49 1 0 16 50 1 0 17 51 1 0 20 52 1 0 21 53 1 0 22 54 1 0 M END

Standard InCHIKey	JUSVGHZRAMJHHC-ZHACJKMWSA-N
Standard InCHI	InChI=1S/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-18-15-16-19(21)20(22)17-18/h10-11,15-17,21-22H,2-9,12-14H2,1H3/b11-10+
SMILES	CCCCCCCCC/C=C/CCCc1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	304.24	Volume:	352.954 ? Van der Waals volume.
Dense:	0.862	LogP:	6.673 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.141 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.892 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	7.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.277	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.188	Fsp³:	0.6
MCE-18:	6.0 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.804	Fluc inhibitor:	0.338 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.152 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.969	Promiscuous compounds:	0.088

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.001	MDCK Permeability:	-4.695
Pgp-inhibitor:	0.093	Pgp-substrate:	0.007
PAMPA:	0.001 ? 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):	0.441
20% Bioavailability (F20%):	0.976	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.338
Plasma Protein Binding (PPB):	98.606%	Volume Distribution (VD):	-0.35
Fu:	0.472% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.856
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.665
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.997
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.162
CYP2C9-inhibitor:	0.761	CYP2C9-substrate:	0.571
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.838 ? 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):

8.024

Half-life (T1/2):

0.686

ADMET: Toxicity

hERG Blockers:	0.459	hERG Blockers (10um):	0.907
Human Hepatotoxicity (H-HT):	0.709	Drug-induced Liver Injury (DILI):	0.056
AMES Toxicity:	0.068	Rat Oral Acute Toxicity:	0.065
Maximum Recommended Daily Dose:	0.511	Skin Sensitization:	1.0
Carcinogencity:	0.065	Eye Corrosion:	0.532
Eye Irritation:	0.985	Respiratory Toxicity:	0.82
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.464
Hematotoxicity:	0.046	Drug-induced Nephrotoxicity:	0.098
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.966	Hek293 Cytotoxicity:	0.585
BCF:	1.629 ? 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:	5.377 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.366 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.963 ? 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
NPO22658	Piper obliquum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18276144]
NPO22658	Piper obliquum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22658	Piper obliquum	Species	Piperaceae	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

Activity Type	# Activity
IC50	1
MIC	2

Activity Type	# Activity
Organism	2
Others	1

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
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	5.0	ug.mL-1	PMID[22316191]
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	MIC	=	5.0	ug.mL-1	PMID[17888665]
NPT2	Others	Unspecified	n.a.	IC50	=	5000.0	nM	PMID[24033131]

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

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 NPC196479 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	24625
0.1-0.2	22129
0.2-0.3	2712
0.3-0.4	269
0.4-0.5	77
0.5-0.6	34
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7632	Intermediate Similarity	NPC55561
0.7368	Intermediate Similarity	NPC177420
0.6667	Remote Similarity	NPC94139
0.6667	Remote Similarity	NPC147284
0.6429	Remote Similarity	NPC483454
0.6429	Remote Similarity	NPC162314
0.6279	Remote Similarity	NPC488416
0.6154	Remote Similarity	NPC25493
0.6047	Remote Similarity	NPC166761
0.5952	Remote Similarity	NPC280347
0.5952	Remote Similarity	NPC146798
0.5952	Remote Similarity	NPC222522
0.5952	Remote Similarity	NPC106396
0.5952	Remote Similarity	NPC94351
0.5952	Remote Similarity	NPC168303
0.587	Remote Similarity	NPC210497
0.5814	Remote Similarity	NPC232523
0.5814	Remote Similarity	NPC487734
0.5714	Remote Similarity	NPC53051
0.5714	Remote Similarity	NPC24404
0.5714	Remote Similarity	NPC313030
0.5714	Remote Similarity	NPC39664
0.5682	Remote Similarity	NPC488413
0.5682	Remote Similarity	NPC488412
0.5556	Remote Similarity	NPC71002
0.5556	Remote Similarity	NPC249828
0.525	Remote Similarity	NPC123273
0.525	Remote Similarity	NPC318325
0.5238	Remote Similarity	NPC470700
0.5238	Remote Similarity	NPC54844
0.5238	Remote Similarity	NPC39097
0.5238	Remote Similarity	NPC302681
0.5238	Remote Similarity	NPC118286
0.5238	Remote Similarity	NPC113460
0.5238	Remote Similarity	NPC3358
0.5238	Remote Similarity	NPC109691
0.5238	Remote Similarity	NPC306884
0.5238	Remote Similarity	NPC603092
0.5217	Remote Similarity	NPC302219
0.5217	Remote Similarity	NPC129373
0.5208	Remote Similarity	NPC192
0.5111	Remote Similarity	NPC120982
0.5106	Remote Similarity	NPC158253

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC196479 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5243
0.1-0.2	3703
0.2-0.3	171
0.3-0.4	28
0.4-0.5	5
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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