NPASS Compound

Natural Product: NPC59474

Natural Product ID	NPC59474
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IKUQEFGEUOOPGY-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	12302276
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives [CHEMONTID:0001743] Coumarin glycosides

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 47 49 0 0 0 0 0 0 0 0999 V2000 0.9996 3.5731 0.9051 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5432 2.2589 0.7961 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4324 1.2004 0.7620 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7879 1.4370 0.8362 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7083 0.4080 0.8055 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0651 0.6315 0.8788 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9211 -0.4402 0.8425 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3501 -1.6997 0.7322 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1189 -2.6948 0.6974 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0443 -1.8522 0.6659 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1972 -0.8663 0.6968 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8332 -1.1303 0.6204 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9317 -0.1032 0.6519 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4481 -0.2459 0.5837 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1796 -0.2343 -0.6442 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8759 -1.5352 -0.8096 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3723 -1.3195 -0.7418 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6254 -0.4133 0.4441 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9942 0.9386 0.1940 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0798 1.8377 -0.3648 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5449 3.1255 -0.6002 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9842 0.8839 -0.7508 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0294 -1.0164 1.5496 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8197 -0.7372 -1.9093 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6257 -2.0419 -2.1044 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3595 -2.4276 0.5121 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1942 -2.9668 -0.7844 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1330 4.2446 0.9864 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6383 3.7903 0.0213 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6405 3.7141 1.7976 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1805 2.4393 0.9212 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4554 1.6332 0.9637 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0073 -0.3380 0.8959 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4095 -0.1309 -1.4398 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5620 -2.2912 -0.0382 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9058 -2.2754 -0.5181 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7153 -0.3515 0.6322 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6727 1.3783 1.1603 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3805 1.4651 -1.3658 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9593 1.9039 0.3258 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4923 3.6159 0.2476 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1453 -2.0021 1.5360 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7807 -0.8005 -2.0495 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4962 -1.2390 -2.6707 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3560 -3.6640 -0.8555 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0639 -2.1618 -1.5449 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1374 -3.5000 -1.1022 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 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 1 0 20 21 1 0 19 22 1 0 18 23 1 0 17 24 1 0 16 25 1 0 12 26 1 0 26 27 1 0 13 3 1 0 22 15 1 0 11 5 2 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 6 32 1 0 7 33 1 0 15 34 1 0 16 35 1 0 17 36 1 0 18 37 1 0 19 38 1 0 20 39 1 0 20 40 1 0 21 41 1 0 23 42 1 0 24 43 1 0 25 44 1 0 27 45 1 0 27 46 1 0 27 47 1 0 M END

Standard InCHIKey	IKUQEFGEUOOPGY-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H20O10/c1-23-8-5-7-3-4-10(19)26-14(7)16(24-2)15(8)27-17-13(22)12(21)11(20)9(6-18)25-17/h3-5,9,11-13,17-18,20-22H,6H2,1-2H3
SMILES	COc1cc2ccc(=O)oc2c(c1OC1C(C(C(C(CO)O1)O)O)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	384.11	Volume:	351.639 ? Van der Waals volume.
Dense:	1.092	LogP:	-1.033 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.202 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.783 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	18.0
TPSA:	148.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.473	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.801	Fsp³:	0.471
MCE-18:	68.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.247	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.874 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.576 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.111	Promiscuous compounds:	0.364

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.984	MDCK Permeability:	-5.185
Pgp-inhibitor:	0.0	Pgp-substrate:	0.002
PAMPA:	0.995 ? 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):	0.188
20% Bioavailability (F20%):	0.836	30% Bioavailability (F30%):	0.941
50% Bioavailability (F50%):	0.814

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.998
Plasma Protein Binding (PPB):	63.565%	Volume Distribution (VD):	-0.391
Fu:	36.915% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.043
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.0
BSEP inhibitor:	0.273

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.448	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.123	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.064
HLM stability:	0.003 ? 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):

3.548

Half-life (T1/2):

2.277

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.257
Human Hepatotoxicity (H-HT):	0.491	Drug-induced Liver Injury (DILI):	0.693
AMES Toxicity:	0.52	Rat Oral Acute Toxicity:	0.295
Maximum Recommended Daily Dose:	0.309	Skin Sensitization:	0.123
Carcinogencity:	0.516	Eye Corrosion:	0.0
Eye Irritation:	0.157	Respiratory Toxicity:	0.117
Drug-induced Neurotoxicity:	0.309	Ototoxicity:	0.819
Hematotoxicity:	0.176	Drug-induced Nephrotoxicity:	0.16
Genotoxicity:	0.502	RPMI-8226 Immunitoxicity:	0.117
A549 Cytotoxicity:	0.032	Hek293 Cytotoxicity:	0.321
BCF:	0.198 ? 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:	2.526 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.191 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.27 ? 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
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[17125224]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	leaves	n.a.	n.a.	PMID[27400231]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC59474 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	27161
0.1-0.2	19568
0.2-0.3	2248
0.3-0.4	716
0.4-0.5	133
0.5-0.6	20
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
0.7258	Intermediate Similarity	NPC52740
0.7143	Intermediate Similarity	NPC96294
0.697	Remote Similarity	NPC213197
0.6447	Remote Similarity	NPC215060
0.6308	Remote Similarity	NPC604162
0.6061	Remote Similarity	NPC103409
0.5942	Remote Similarity	NPC212670
0.5942	Remote Similarity	NPC206264
0.5915	Remote Similarity	NPC38438
0.5893	Remote Similarity	NPC244799
0.5875	Remote Similarity	NPC476352
0.5797	Remote Similarity	NPC41844
0.5781	Remote Similarity	NPC479800
0.5732	Remote Similarity	NPC485744
0.5696	Remote Similarity	NPC284810
0.5682	Remote Similarity	NPC169645
0.56	Remote Similarity	NPC85624
0.5541	Remote Similarity	NPC611276
0.541	Remote Similarity	NPC601808
0.5402	Remote Similarity	NPC485746
0.5294	Remote Similarity	NPC485745
0.5246	Remote Similarity	NPC217854
0.5135	Remote Similarity	NPC205361
0.5082	Remote Similarity	NPC276195
0.5079	Remote Similarity	NPC152722
0.5068	Remote Similarity	NPC15577

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC59474 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5731
0.1-0.2	3303
0.2-0.3	104
0.3-0.4	10
0.4-0.5	1
0.5-0.6	1
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
0.5942	Remote Similarity	NPD1653	Approved

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