NPASS Compound

Natural Product: NPC302681

Natural Product ID	NPC302681
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-[(Z)-14-(3,5-Dihydroxyphenyl)Tetradec-8-Enyl]Benzene-1,3-Diol
IUPAC Name	5-[(Z)-14-(3,5-dihydroxyphenyl)tetradec-8-enyl]benzene-1,3-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL465325
PubChem CID	10525745
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0001286] Benzenediols [CHEMONTID:0000137] Resorcinols

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 66 67 0 0 0 0 0 0 0 0999 V2000 -9.7696 1.3997 2.7236 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.9249 1.1512 1.6297 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6483 0.6614 1.8239 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8591 0.4347 0.7134 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4566 -0.1014 0.8965 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5312 -1.6029 0.8695 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1572 -2.1776 1.0649 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2524 -1.7107 -0.0330 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8518 -2.2754 0.1044 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0145 -1.7795 -1.0338 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9120 -0.2778 -1.0683 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0667 0.1098 -2.1969 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0542 0.7820 -2.1146 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6029 1.2343 -0.8393 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9873 0.6581 -0.5655 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9686 1.0516 -1.6204 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3511 0.4953 -1.3860 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8652 0.9973 -0.0790 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2313 0.5006 0.2339 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4916 -0.6500 0.9134 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7973 -1.0511 1.1691 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0617 -2.2240 1.8617 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8412 -0.2522 0.7163 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6035 0.9264 0.0206 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2888 1.2793 -0.2069 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6656 1.7255 -0.4320 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3518 0.6968 -0.5439 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6220 1.1858 -0.7637 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4025 1.4076 0.3734 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1332 1.4549 -2.0232 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.9916 2.3893 2.8635 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2745 0.4603 2.8156 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8955 0.3027 0.0291 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1184 0.2345 1.8739 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2390 -1.9792 1.6375 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9196 -1.8745 -0.1500 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1830 -3.2937 1.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7871 -1.8522 2.0590 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1231 -0.5992 0.1321 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6720 -1.9636 -1.0078 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8751 -3.3794 0.0958 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3969 -1.9265 1.0666 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0140 -2.2682 -1.0458 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4875 -2.0807 -2.0101 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9636 0.0723 -1.3443 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7206 0.1745 -0.1061 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4326 -0.2070 -3.1979 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5913 1.0091 -3.0279 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7790 2.3568 -0.8375 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0146 1.0512 0.0582 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9626 -0.4228 -0.3541 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3090 1.1571 0.3951 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0765 2.1733 -1.5605 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6137 0.8259 -2.6503 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3677 -0.6125 -1.4161 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9866 0.8532 -2.2210 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7805 2.0938 -0.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2197 0.5820 0.7465 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6704 -1.2558 1.2563 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2770 -3.0857 1.3919 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8620 -0.5631 0.9146 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1079 2.2147 -0.7589 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0376 2.3682 0.2833 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7237 0.5151 -1.4070 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4035 1.7938 0.1850 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2911 0.6867 -2.6844 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 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 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 21 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 4 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 29 2 1 0 25 19 1 0 1 31 1 0 3 32 1 0 5 33 1 0 5 34 1 0 6 35 1 0 6 36 1 0 7 37 1 0 7 38 1 0 8 39 1 0 8 40 1 0 9 41 1 0 9 42 1 0 10 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 12 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 15 51 1 0 15 52 1 0 16 53 1 0 16 54 1 0 17 55 1 0 17 56 1 0 18 57 1 0 18 58 1 0 20 59 1 0 22 60 1 0 23 61 1 0 25 62 1 0 26 63 1 0 27 64 1 0 29 65 1 0 30 66 1 0 M END

Standard InCHIKey	INRCFVYVWPWZJS-IWQZZHSRSA-N
Standard InCHI	InChI=1S/C26H36O4/c27-23-15-21(16-24(28)19-23)13-11-9-7-5-3-1-2-4-6-8-10-12-14-22-17-25(29)20-26(30)18-22/h1,3,15-20,27-30H,2,4-14H2/b3-1-
SMILES	Oc1cc(CCCCCCC/C=CCCCCCc2cc(O)cc(c2)O)cc(c1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	412.26	Volume:	457.845 ? Van der Waals volume.
Dense:	0.9	LogP:	6.863 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.919 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.901 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	13.0
TPSA:	80.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.204	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.414	Fsp³:	0.462
MCE-18:	12.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.955	Fluc inhibitor:	0.436 ? 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:	0.072 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.668	Promiscuous compounds:	0.114

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.046	MDCK Permeability:	-4.733
Pgp-inhibitor:	0.245	Pgp-substrate:	0.0
PAMPA:	0.0 ? 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%):	0.732	30% Bioavailability (F30%):	0.851
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.696
Plasma Protein Binding (PPB):	98.595%	Volume Distribution (VD):	0.165
Fu:	0.563% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.308
OATP1B3 inhibitor:	0.954	BCRP inhibitor:	0.724
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.16	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.375	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.047	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.991 ? 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):

2.457

Half-life (T1/2):

1.618

ADMET: Toxicity

hERG Blockers:	0.804	hERG Blockers (10um):	0.913
Human Hepatotoxicity (H-HT):	0.37	Drug-induced Liver Injury (DILI):	0.001
AMES Toxicity:	0.265	Rat Oral Acute Toxicity:	0.123
Maximum Recommended Daily Dose:	0.856	Skin Sensitization:	1.0
Carcinogencity:	0.067	Eye Corrosion:	0.868
Eye Irritation:	0.998	Respiratory Toxicity:	0.66
Drug-induced Neurotoxicity:	0.021	Ototoxicity:	0.148
Hematotoxicity:	0.004	Drug-induced Nephrotoxicity:	0.123
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.068
A549 Cytotoxicity:	0.95	Hek293 Cytotoxicity:	0.989
BCF:	1.549 ? 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:	5.091 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.195 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.759 ? 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
NPO33313	oncostemon bojerianum	Species	n.a.	n.a.	leaves	Madagascar rainforest	n.a.	PMID[12444688]

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

Activity Type	# Activity
Cell line	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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	9.8	ug.mL-1	PMID[17428663]

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 NPC302681 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	30977
0.1-0.2	17173
0.2-0.3	1451
0.3-0.4	140
0.4-0.5	38
0.5-0.6	19
0.6-0.7	20
0.7-0.8	0
0.8-0.85	8
0.85-0.9	0
0.9-0.95	9
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC470700
1.0	High Similarity	NPC54844
1.0	High Similarity	NPC39097
1.0	High Similarity	NPC118286
1.0	High Similarity	NPC109691
0.9375	High Similarity	NPC53051
0.9375	High Similarity	NPC24404
0.9375	High Similarity	NPC313030
0.9375	High Similarity	NPC39664
0.9091	High Similarity	NPC146798
0.9091	High Similarity	NPC222522
0.9091	High Similarity	NPC106396
0.9091	High Similarity	NPC94351
0.9091	High Similarity	NPC168303
0.8333	Intermediate Similarity	NPC71002
0.8333	Intermediate Similarity	NPC10588
0.8333	Intermediate Similarity	NPC302219
0.8333	Intermediate Similarity	NPC242342
0.8333	Intermediate Similarity	NPC249828
0.8333	Intermediate Similarity	NPC85479
0.8108	Intermediate Similarity	NPC72947
0.8	Intermediate Similarity	NPC246056
0.7838	Intermediate Similarity	NPC284011
0.7273	Intermediate Similarity	NPC294186
0.7273	Intermediate Similarity	NPC147310
0.7273	Intermediate Similarity	NPC137415
0.7273	Intermediate Similarity	NPC166313
0.7273	Intermediate Similarity	NPC192032
0.7273	Intermediate Similarity	NPC24407
0.7273	Intermediate Similarity	NPC11280
0.7105	Intermediate Similarity	NPC166761
0.6977	Remote Similarity	NPC305603
0.6977	Remote Similarity	NPC61033
0.6977	Remote Similarity	NPC127894
0.6977	Remote Similarity	NPC470759
0.6667	Remote Similarity	NPC241891
0.6667	Remote Similarity	NPC483454
0.6667	Remote Similarity	NPC134829
0.6667	Remote Similarity	NPC162314
0.6512	Remote Similarity	NPC470760
0.65	Remote Similarity	NPC94139
0.65	Remote Similarity	NPC147284
0.641	Remote Similarity	NPC232523
0.6383	Remote Similarity	NPC140521
0.625	Remote Similarity	NPC488413
0.625	Remote Similarity	NPC488412
0.6047	Remote Similarity	NPC210497
0.6047	Remote Similarity	NPC192
0.6047	Remote Similarity	NPC219070
0.6042	Remote Similarity	NPC123559
0.6	Remote Similarity	NPC486908
0.5952	Remote Similarity	NPC158253
0.5952	Remote Similarity	NPC204901
0.5625	Remote Similarity	NPC470699
0.561	Remote Similarity	NPC487734
0.5581	Remote Similarity	NPC114064
0.5556	Remote Similarity	NPC483450
0.5532	Remote Similarity	NPC249836
0.5532	Remote Similarity	NPC15860
0.5476	Remote Similarity	NPC487735
0.5366	Remote Similarity	NPC55561
0.5349	Remote Similarity	NPC129373
0.5349	Remote Similarity	NPC115808
0.5349	Remote Similarity	NPC488416
0.5333	Remote Similarity	NPC483449
0.525	Remote Similarity	NPC487946
0.525	Remote Similarity	NPC487945
0.5238	Remote Similarity	NPC196479
0.52	Remote Similarity	NPC473221
0.5122	Remote Similarity	NPC177420

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC302681 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6910
0.1-0.2	2134
0.2-0.3	100
0.3-0.4	6
0.4-0.5	0
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