NPASS Compound

Natural Product: NPC81970

Natural Product ID	NPC81970
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UIPQDOWYNRWNGN-WSFKTYETSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5317554
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan lactones

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 43 48 0 0 0 0 0 0 0 0999 V2000 2.4713 -0.9897 -0.6889 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6139 -1.7766 -0.5812 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7959 -1.2115 -0.1867 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8556 0.1290 0.1026 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7066 0.9052 -0.0088 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4896 0.3519 -0.4092 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3403 1.2484 -0.4956 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0017 0.6189 -0.3879 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0389 1.6808 -0.7461 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2577 2.3183 0.4732 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4987 1.2013 1.3095 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6901 0.5314 0.7906 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7849 1.3318 0.4443 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9507 0.8195 -0.0502 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0535 -0.5351 -0.2146 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9956 -1.3510 0.1160 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8372 -0.8162 0.6098 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3974 -2.6596 -0.1589 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6460 -2.6430 -0.8388 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1023 -1.3087 -0.6884 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2157 0.4390 1.0811 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8709 1.2404 1.6948 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2819 1.2116 2.8814 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3679 2.0531 0.6947 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1527 0.4388 0.4718 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9875 -0.5776 -0.0464 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0983 -1.7031 0.0193 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5332 -1.4278 -1.0002 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5764 -2.8190 -0.8040 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7944 1.9568 0.2278 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3534 1.8974 -1.3978 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1503 -0.3016 -0.9762 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5562 2.4080 -1.4508 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9378 1.2389 -1.1835 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6275 1.5033 2.3574 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7307 2.4135 0.5649 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7877 1.4858 -0.3099 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0100 -1.4547 0.8683 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3667 -3.3610 -0.4195 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5279 -2.8255 -1.9082 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2395 -0.5900 1.4273 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2383 -0.3499 -1.0971 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8770 -0.7216 0.5729 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 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 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 11 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 4 25 1 0 25 26 1 0 26 27 1 0 6 1 1 0 24 7 1 0 27 3 1 0 21 8 1 0 17 12 1 0 20 15 1 0 1 28 1 0 2 29 1 0 5 30 1 0 7 31 1 6 8 32 1 6 9 33 1 0 9 34 1 0 11 35 1 1 13 36 1 0 14 37 1 0 17 38 1 0 19 39 1 0 19 40 1 0 21 41 1 6 26 42 1 0 26 43 1 0 M END

Standard InCHIKey	UIPQDOWYNRWNGN-WSFKTYETSA-N
Standard InCHI	InChI=1S/C20H16O7/c21-20-17-12(18(27-20)10-1-3-13-15(5-10)25-8-23-13)7-22-19(17)11-2-4-14-16(6-11)26-9-24-14/h1-6,12,17-19H,7-9H2/t12-,17-,18+,19+/m1/s1
SMILES	c1cc2c(cc1[C@H]1[C@@H]3CO[C@@H](c4ccc5c(c4)OCO5)[C@@H]3C(=O)O1)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	368.09	Volume:	346.214 ? Van der Waals volume.
Dense:	1.063	LogP:	2.274 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.541 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.395 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	30.0
TPSA:	72.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.755	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.805	Fsp³:	0.35
MCE-18:	102.037 ? 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:	0.607	Fluc inhibitor:	0.938 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.042 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.056 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.265	Promiscuous compounds:	0.37

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.072	MDCK Permeability:	-4.684
Pgp-inhibitor:	0.045	Pgp-substrate:	0.0
PAMPA:	0.194 ? 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%):	0.0	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.022

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.946	MRP1:	0.842
Plasma Protein Binding (PPB):	96.807%	Volume Distribution (VD):	-0.064
Fu:	4.435% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.503
OATP1B3 inhibitor:	0.671	BCRP inhibitor:	0.0
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.981	CYP1A2-substrate:	0.994
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.522
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.672	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.857	CYP2C8-inhibitor:	0.0
HLM stability:	0.411 ? 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):

2.818

Half-life (T1/2):

1.883

ADMET: Toxicity

hERG Blockers:	0.112	hERG Blockers (10um):	0.383
Human Hepatotoxicity (H-HT):	0.559	Drug-induced Liver Injury (DILI):	0.975
AMES Toxicity:	0.714	Rat Oral Acute Toxicity:	0.23
Maximum Recommended Daily Dose:	0.382	Skin Sensitization:	0.852
Carcinogencity:	0.823	Eye Corrosion:	0.095
Eye Irritation:	0.968	Respiratory Toxicity:	0.29
Drug-induced Neurotoxicity:	0.352	Ototoxicity:	0.285
Hematotoxicity:	0.516	Drug-induced Nephrotoxicity:	0.716
Genotoxicity:	0.902	RPMI-8226 Immunitoxicity:	0.101
A549 Cytotoxicity:	0.206	Hek293 Cytotoxicity:	0.283
BCF:	1.515 ? 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:	4.169 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.183 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.359 ? 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
NPO1787	Agathis lanceolata	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10765	Dracaena concinna	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17495	Isodon amethystoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13009	Laurencia saitoi	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	Leaf Diffusate	n.a.	n.a.	Database[FooDB]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	Seeds	n.a.		Database[Phenol-Explorer]
NPO3998	Neolitsea pulchella	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17495	Isodon amethystoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29532	Vigna angularis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3998	Neolitsea pulchella	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13009	Laurencia saitoi	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1787	Agathis lanceolata	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14335	Ophiorrhiza kuroiwae	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10542	Liparis keitaoensis	Species	Liparidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10765	Dracaena concinna	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17495	Isodon amethystoides	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3426	Pseudocyphellaria hirsuta	Species	Lobariaceae	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 NPC81970 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	28019
0.1-0.2	20472
0.2-0.3	1027
0.3-0.4	254
0.4-0.5	44
0.5-0.6	25
0.6-0.7	9
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9149	High Similarity	NPC483653
0.7333	Intermediate Similarity	NPC171928
0.7333	Intermediate Similarity	NPC158526
0.7333	Intermediate Similarity	NPC129687
0.7333	Intermediate Similarity	NPC33611
0.7333	Intermediate Similarity	NPC16830
0.7333	Intermediate Similarity	NPC100223
0.6735	Remote Similarity	NPC227160
0.6735	Remote Similarity	NPC82111
0.6735	Remote Similarity	NPC483654
0.6538	Remote Similarity	NPC14022
0.6538	Remote Similarity	NPC601703
0.6471	Remote Similarity	NPC189474
0.6324	Remote Similarity	NPC186316
0.6122	Remote Similarity	NPC480478
0.6	Remote Similarity	NPC469981
0.5893	Remote Similarity	NPC298317
0.5893	Remote Similarity	NPC255566
0.5714	Remote Similarity	NPC223185
0.569	Remote Similarity	NPC88640
0.569	Remote Similarity	NPC101153
0.569	Remote Similarity	NPC193666
0.569	Remote Similarity	NPC123526
0.569	Remote Similarity	NPC608725
0.551	Remote Similarity	NPC271208
0.551	Remote Similarity	NPC233224
0.551	Remote Similarity	NPC610263
0.5472	Remote Similarity	NPC308976
0.541	Remote Similarity	NPC254163
0.5323	Remote Similarity	NPC311057
0.5312	Remote Similarity	NPC308555
0.5306	Remote Similarity	NPC121783
0.5306	Remote Similarity	NPC34902
0.5306	Remote Similarity	NPC18449
0.5254	Remote Similarity	NPC474139
0.5167	Remote Similarity	NPC47181
0.5094	Remote Similarity	NPC57119
0.5094	Remote Similarity	NPC158471
0.5094	Remote Similarity	NPC226862
0.5094	Remote Similarity	NPC606146
0.5085	Remote Similarity	NPC101807

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC81970 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4507
0.1-0.2	4542
0.2-0.3	93
0.3-0.4	8
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