NPASS Compound

Natural Product: NPC71256

Natural Product ID	NPC71256
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-[(Z,10R)-10-Acetyloxypentadec-8-Enyl]-4,6-Dihydroxybenzoic Acid
IUPAC Name	2-[(Z,10R)-10-acetyloxypentadec-8-enyl]-4,6-dihydroxybenzoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL479137
PubChem CID	44584497
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001722] Fatty alcohol esters

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 66 0 0 0 0 0 0 0 0999 V2000 -8.2943 -3.1552 -1.3297 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9915 -2.3603 -1.2978 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2161 -0.9392 -0.8984 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9437 -0.1700 -0.8715 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9859 -0.7717 0.1046 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6641 0.0360 0.1330 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0823 1.3407 0.5287 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0978 2.4429 -0.2797 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7201 2.3230 -1.4759 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5517 3.7929 0.2155 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8145 -0.6011 1.1431 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5218 -0.3438 1.1789 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9261 0.5743 0.2165 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2834 1.7554 0.9516 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7847 1.3368 1.8830 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9421 0.6196 1.2472 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6636 1.3993 0.2227 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7864 0.5809 -0.3662 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8161 0.1477 0.6455 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9282 -0.6330 0.0132 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8441 -2.0313 0.0542 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8347 -2.7860 -0.5343 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7748 -4.1590 -0.5074 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9092 -2.1858 -1.1637 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0080 -0.8254 -1.2131 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0036 -0.0640 -0.6161 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1385 1.3847 -0.6597 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7040 2.1216 -1.5618 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8218 1.9536 0.4256 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0617 -0.1674 -1.8298 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9779 -4.2360 -1.3502 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8382 -2.9638 -0.3955 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8715 -2.9917 -2.2402 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5582 -2.4447 -2.3090 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3747 -2.8513 -0.5180 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9735 -0.4494 -1.5717 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6235 -0.9420 0.1542 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1891 0.8706 -0.5172 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5053 -0.0866 -1.8971 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6628 -1.7743 -0.2926 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4479 -0.8191 1.0895 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3158 -0.0175 -0.9062 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6196 4.4819 -0.6360 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7859 4.2053 0.9220 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5398 3.7375 0.7012 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2423 -1.3016 1.8860 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8501 -0.8045 1.9248 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5595 0.9419 -0.5807 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0607 0.0669 -0.3044 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0222 2.5063 0.1981 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1002 2.2185 1.5434 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3396 0.6855 2.6626 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1810 2.2267 2.4120 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5930 -0.3337 0.8094 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6681 0.3271 2.0627 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1304 2.3342 0.5982 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9812 1.6167 -0.6483 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3811 -0.3351 -0.8804 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2936 1.1705 -1.1491 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3078 1.0158 1.1368 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3306 -0.4909 1.4367 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9954 -2.4690 0.5517 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2017 -4.6788 -1.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7015 -2.7770 -1.6346 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8155 2.9295 0.6162 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2255 0.8156 -1.6468 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 2 0 8 10 1 0 6 11 1 0 11 12 2 0 12 13 1 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 1 0 20 21 2 0 21 22 1 0 22 23 1 0 22 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 27 29 1 0 25 30 1 0 26 20 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 2 35 1 0 3 36 1 0 3 37 1 0 4 38 1 0 4 39 1 0 5 40 1 0 5 41 1 0 6 42 1 6 10 43 1 0 10 44 1 0 10 45 1 0 11 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 14 50 1 0 14 51 1 0 15 52 1 0 15 53 1 0 16 54 1 0 16 55 1 0 17 56 1 0 17 57 1 0 18 58 1 0 18 59 1 0 19 60 1 0 19 61 1 0 21 62 1 0 23 63 1 0 24 64 1 0 29 65 1 0 30 66 1 0 M END

Standard InCHIKey	SBXHSSAGYGUAKV-OKULMJQMSA-N
Standard InCHI	InChI=1S/C24H36O6/c1-3-4-10-14-21(30-18(2)25)15-12-9-7-5-6-8-11-13-19-16-20(26)17-22(27)23(19)24(28)29/h12,15-17,21,26-27H,3-11,13-14H2,1-2H3,(H,28,29)/b15-12-/t21-/m1/s1
SMILES	CCCCC[C@@H](OC(=O)C)/C=CCCCCCCCc1cc(O)cc(c1C(=O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	420.25	Volume:	452.026 ? Van der Waals volume.
Dense:	0.93	LogP:	6.275 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.535 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.077 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	9.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	1.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.19	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.182	Fsp³:	0.583
MCE-18:	20.0 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.459	Fluc inhibitor:	0.211 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.084 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.133 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.541	Promiscuous compounds:	0.342

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.202	MDCK Permeability:	-4.803
Pgp-inhibitor:	0.259	Pgp-substrate:	0.138
PAMPA:	0.251 ? 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):	0.034
20% Bioavailability (F20%):	0.679	30% Bioavailability (F30%):	0.979
50% Bioavailability (F50%):	0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.856
Plasma Protein Binding (PPB):	98.335%	Volume Distribution (VD):	-0.44
Fu:	1.059% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.771
OATP1B3 inhibitor:	0.886	BCRP inhibitor:	0.237
BSEP inhibitor:	0.979

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.347
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.631
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.905 ? 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):

3.007

Half-life (T1/2):

1.061

ADMET: Toxicity

hERG Blockers:	0.145	hERG Blockers (10um):	0.236
Human Hepatotoxicity (H-HT):	0.522	Drug-induced Liver Injury (DILI):	0.112
AMES Toxicity:	0.173	Rat Oral Acute Toxicity:	0.174
Maximum Recommended Daily Dose:	0.229	Skin Sensitization:	0.996
Carcinogencity:	0.057	Eye Corrosion:	0.866
Eye Irritation:	0.995	Respiratory Toxicity:	0.841
Drug-induced Neurotoxicity:	0.022	Ototoxicity:	0.304
Hematotoxicity:	0.078	Drug-induced Nephrotoxicity:	0.618
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.675	Hek293 Cytotoxicity:	0.191
BCF:	1.341 ? 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:	4.838 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.09 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.721 ? 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
NPO21579	Ononis speciosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8277313]
NPO21579	Ononis speciosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21579	Ononis speciosa	Species	Fabaceae	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
IZ	12

Activity Type	# Activity
Organism	12

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
NPT4085	Organism	Bacillus licheniformis	Bacillus licheniformis	IZ	=	22.0	mm	PMID[7852999]
NPT4085	Organism	Bacillus licheniformis	Bacillus licheniformis	IZ	=	18.0	mm	PMID[7852999]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	IZ	=	13.0	mm	PubChem BioAssay data set
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	8.0	mm	PubChem BioAssay data set
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	7.0	mm	PubChem BioAssay data set
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	IZ	=	15.0	mm	PMID[7852999]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	IZ	=	13.0	mm	PMID[11689078]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	7.0	mm	PubChem BioAssay data set
NPT4084	Organism	Bacillus circulans	Bacillus circulans	IZ	=	9.0	mm	PMID[7506311]
NPT4084	Organism	Bacillus circulans	Bacillus circulans	IZ	=	8.0	mm	PMID[17125224]
NPT1230	Organism	Bacillus megaterium	Bacillus megaterium	IZ	=	7.0	mm	PMID[22148349]

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 NPC71256 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	10069
0.1-0.2	37207
0.2-0.3	2408
0.3-0.4	127
0.4-0.5	31
0.5-0.6	10
0.6-0.7	4
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
0.7458	Intermediate Similarity	NPC17840
0.7458	Intermediate Similarity	NPC247477
0.6667	Remote Similarity	NPC123559
0.6212	Remote Similarity	NPC486907
0.6102	Remote Similarity	NPC607458
0.6	Remote Similarity	NPC486906
0.5373	Remote Similarity	NPC244994
0.5373	Remote Similarity	NPC222876
0.5373	Remote Similarity	NPC292665
0.5373	Remote Similarity	NPC179092
0.5303	Remote Similarity	NPC487950
0.5224	Remote Similarity	NPC238531
0.5224	Remote Similarity	NPC178395
0.5167	Remote Similarity	NPC201728
0.5143	Remote Similarity	NPC301987
0.5075	Remote Similarity	NPC483452

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC71256 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3490
0.1-0.2	5508
0.2-0.3	150
0.3-0.4	2
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