NPASS Compound

Natural Product: NPC277493

Natural Product ID	NPC277493
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ANCVHDRNDJRUOT-FBJOKTGGSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5315944
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003422] 7,9'-epoxylignans

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 57 59 0 0 0 0 0 0 0 0999 V2000 3.1806 3.9271 -0.8900 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3815 3.2294 -0.6964 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3137 1.8908 -0.2839 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1041 1.2637 -0.0702 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0515 -0.0518 0.3349 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2475 -0.7074 0.5156 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4737 -0.0774 0.3008 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5158 1.2403 -0.1049 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7395 1.8876 -0.3250 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6720 -0.7330 0.4815 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8312 -2.0565 0.8857 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7648 -0.7542 0.5716 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8405 -1.9425 0.9418 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4838 -0.1063 0.3866 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2508 0.3764 -1.0310 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8198 -0.2783 -1.5598 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4629 -0.9935 -0.6059 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8406 -0.4782 -0.4198 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8919 -1.3722 -0.3467 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1814 -0.9486 -0.1742 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4236 0.4222 -0.0717 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4149 1.3437 -0.1384 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1154 0.8690 -0.3148 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6394 2.7108 -0.0382 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5797 3.6191 -0.1117 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7183 0.8832 0.1034 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1978 -1.8628 -0.1062 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9490 -3.2355 -0.2096 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6925 -0.8981 0.7003 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4981 -2.2814 1.2602 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7784 -2.8713 1.5055 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4314 4.9373 -1.2624 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5049 3.4093 -1.6121 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6532 4.0443 0.0887 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2016 1.8321 -0.2282 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2154 -1.7412 0.8336 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4850 1.6425 0.3259 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8588 -2.7001 -0.0179 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7891 -2.2390 1.4251 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0087 -2.3847 1.5526 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4919 0.7947 1.0873 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1405 0.2003 -1.6627 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0223 1.4736 -1.0176 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5089 -2.0567 -0.9311 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6743 -2.4367 -0.4307 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3226 1.6045 -0.3665 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8559 3.4727 0.7046 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9604 4.6566 -0.0314 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0220 3.5145 -1.0738 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4668 0.2458 0.2766 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1530 -3.5053 0.5194 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6025 -3.4910 -1.2234 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8555 -3.8243 0.0368 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3729 -0.3728 1.4363 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0437 -2.9706 0.5303 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0363 -2.3240 2.2083 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6032 -3.7961 1.8209 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 7 10 1 0 10 11 1 0 5 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 21 26 1 0 20 27 1 0 27 28 1 0 17 29 1 0 29 30 1 0 30 31 1 0 8 3 1 0 29 14 1 0 23 18 1 0 1 32 1 0 1 33 1 0 1 34 1 0 4 35 1 0 6 36 1 0 9 37 1 0 11 38 1 0 11 39 1 0 11 40 1 0 14 41 1 1 15 42 1 0 15 43 1 0 17 44 1 6 19 45 1 0 23 46 1 0 25 47 1 0 25 48 1 0 25 49 1 0 26 50 1 0 28 51 1 0 28 52 1 0 28 53 1 0 29 54 1 1 30 55 1 0 30 56 1 0 31 57 1 0 M END

Standard InCHIKey	ANCVHDRNDJRUOT-FBJOKTGGSA-N
Standard InCHI	InChI=1S/C22H26O9/c1-27-15-5-11(6-16(28-2)20(15)25)19(24)14-10-31-22(13(14)9-23)12-7-17(29-3)21(26)18(8-12)30-4/h5-8,13-14,22-23,25-26H,9-10H2,1-4H3/t13-,14-,22+/m0/s1
SMILES	COc1cc(cc(c1O)OC)C(=O)[C@H]1CO[C@H](c2cc(c(c(c2)OC)O)OC)[C@H]1CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	434.16	Volume:	424.056 ? Van der Waals volume.
Dense:	1.024	LogP:	1.131 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.461 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.777 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	18.0
TPSA:	123.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.537	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.631	Fsp³:	0.409
MCE-18:	68.419 ? 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:	0.066	Fluc inhibitor:	0.157 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.021 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.363 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.157	Promiscuous compounds:	0.554

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.698	MDCK Permeability:	-5.207
Pgp-inhibitor:	0.698	Pgp-substrate:	0.219
PAMPA:	0.007 ? 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):	0.005
20% Bioavailability (F20%):	0.012	30% Bioavailability (F30%):	0.004
50% Bioavailability (F50%):	0.8

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.069	MRP1:	0.986
Plasma Protein Binding (PPB):	83.671%	Volume Distribution (VD):	-0.286
Fu:	17.803% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.872
BSEP inhibitor:	0.773

ADMET: Metabolism

CYP1A2-inhibitor:	0.56	CYP1A2-substrate:	0.234
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.628
CYP2C9-inhibitor:	0.887	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.019
CYP3A4-inhibitor:	0.044	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.769 ? 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):

6.438

Half-life (T1/2):

1.965

ADMET: Toxicity

hERG Blockers:	0.068	hERG Blockers (10um):	0.263
Human Hepatotoxicity (H-HT):	0.732	Drug-induced Liver Injury (DILI):	0.838
AMES Toxicity:	0.691	Rat Oral Acute Toxicity:	0.336
Maximum Recommended Daily Dose:	0.261	Skin Sensitization:	0.913
Carcinogencity:	0.53	Eye Corrosion:	0.007
Eye Irritation:	0.796	Respiratory Toxicity:	0.4
Drug-induced Neurotoxicity:	0.516	Ototoxicity:	0.399
Hematotoxicity:	0.511	Drug-induced Nephrotoxicity:	0.582
Genotoxicity:	0.783	RPMI-8226 Immunitoxicity:	0.205
A549 Cytotoxicity:	0.181	Hek293 Cytotoxicity:	0.361
BCF:	0.78 ? 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:	3.479 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.517 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.963 ? 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
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[17125224]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	leaves and twigs	n.a.	n.a.	PMID[21435874]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27128895]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	leaves	n.a.	n.a.	PMID[27400231]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	Resinous Wood	n.a.	n.a.	PMID[29227647]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38792158]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29118	Euonymus alatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11872	Eleutherococcus senticosus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	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 NPC277493 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	16999
0.1-0.2	29448
0.2-0.3	3134
0.3-0.4	207
0.4-0.5	48
0.5-0.6	13
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	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC287504
1.0	High Similarity	NPC611302
0.6545	Remote Similarity	NPC62354
0.6481	Remote Similarity	NPC30890
0.623	Remote Similarity	NPC25127
0.6032	Remote Similarity	NPC475738
0.5902	Remote Similarity	NPC151425
0.5833	Remote Similarity	NPC141765
0.5833	Remote Similarity	NPC244983
0.5833	Remote Similarity	NPC34103
0.5738	Remote Similarity	NPC600032
0.541	Remote Similarity	NPC486558
0.5283	Remote Similarity	NPC165155
0.5283	Remote Similarity	NPC326095
0.5283	Remote Similarity	NPC24490
0.5179	Remote Similarity	NPC27159
0.5179	Remote Similarity	NPC479434
0.5179	Remote Similarity	NPC186220
0.5161	Remote Similarity	NPC282833

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC277493 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3543
0.1-0.2	5498
0.2-0.3	108
0.3-0.4	1
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