NPASS Compound

Natural Product: NPC476166

Natural Product ID	NPC476166
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lespeflorin G6
IUPAC Name	(6aR,11aR)-9-methoxy-8-methyl-10-(3-methylbut-2-enyl)-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromen-3-ol
Synonyms	Lespeflorin G6
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL550223
PubChem CID	45270490
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002617] Furanoisoflavonoids [CHEMONTID:0001608] Pterocarpans

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 50 53 0 0 0 0 0 0 0 0999 V2000 -2.8881 -2.8063 -2.2426 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8317 -1.4152 -2.3368 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6972 -0.6608 -2.0572 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8203 -0.4059 -3.1001 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1124 -0.9351 -4.4574 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3135 0.3370 -2.8638 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6009 0.8386 -1.6035 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2862 0.5708 -0.5857 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4364 -0.1746 -0.7931 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3927 -0.4621 0.3044 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9424 0.0874 1.6029 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6465 0.9794 2.2835 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1444 1.4971 3.5846 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9543 1.5006 1.7903 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1871 1.1624 0.5916 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5559 1.4913 0.4267 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7014 1.6500 -1.0410 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0346 1.2123 -1.5958 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2682 -0.1167 -1.1304 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2942 -0.2785 0.2682 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4562 0.5085 1.0295 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4868 0.3450 2.3964 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3233 -0.5749 3.0296 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1508 -1.3503 2.2600 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1253 -1.1925 0.8971 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9855 -2.2653 2.8612 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3270 -3.1397 -1.2918 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4520 -3.2428 -3.1176 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8653 -3.2816 -2.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1782 -0.6351 -4.6807 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0072 -2.0357 -4.5212 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5022 -0.4720 -5.2357 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0331 0.5642 -3.6501 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3477 0.0763 0.0314 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6497 -1.5387 0.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0009 -0.2549 2.0114 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8644 1.2932 4.4032 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1601 1.0393 3.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9810 2.5853 3.5037 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8736 1.9298 0.7704 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3311 2.2858 2.4430 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6612 0.6236 1.8080 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7057 2.4891 0.9204 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4720 2.7082 -1.3084 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9441 1.2040 -2.7009 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7957 1.9250 -1.2180 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8527 0.9343 3.0380 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3120 -0.6685 4.1191 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7833 -1.8074 0.2626 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9719 -2.1239 3.0076 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 4 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 3 12 13 1 0 12 14 1 0 8 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 2 0 23 24 1 0 24 25 2 0 24 26 1 0 9 3 1 0 21 16 1 0 17 7 1 0 25 20 1 0 1 27 1 0 1 28 1 0 1 29 1 0 5 30 1 0 5 31 1 0 5 32 1 0 6 33 1 0 10 34 1 0 10 35 1 0 11 36 1 0 13 37 1 0 13 38 1 0 13 39 1 0 14 40 1 0 14 41 1 0 14 42 1 0 16 43 1 1 17 44 1 1 18 45 1 0 18 46 1 0 22 47 1 0 23 48 1 0 25 49 1 0 26 50 1 0 M END

Standard InCHIKey	AUTKSCVETOWBRA-RXVVDRJESA-N
Standard InCHI	InChI=1S/C22H24O4/c1-12(2)5-7-16-20(24-4)13(3)9-17-18-11-25-19-10-14(23)6-8-15(19)21(18)26-22(16)17/h5-6,8-10,18,21,23H,7,11H2,1-4H3/t18-,21-/m0/s1
SMILES	COc1c(C)cc2c(c1CC=C(C)C)O[C@@H]1[C@H]2COc2c1ccc(c2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	352.17	Volume:	371.548 ? Van der Waals volume.
Dense:	0.948	LogP:	4.808 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.962 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.654 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	21.0
TPSA:	47.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.804	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.685	Fsp³:	0.364
MCE-18:	73.6 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.971	Fluc inhibitor:	0.846 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.424 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.36 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.229	Promiscuous compounds:	0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.735	MDCK Permeability:	-4.724
Pgp-inhibitor:	0.204	Pgp-substrate:	0.474
PAMPA:	0.082 ? 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):	0.001
20% Bioavailability (F20%):	0.929	30% Bioavailability (F30%):	0.942
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.382	MRP1:	0.976
Plasma Protein Binding (PPB):	94.831%	Volume Distribution (VD):	0.301
Fu:	5.033% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.967	BCRP inhibitor:	0.475
BSEP inhibitor:	0.967

ADMET: Metabolism

CYP1A2-inhibitor:	0.011	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.029	CYP2C9-substrate:	0.656
CYP2D6-inhibitor:	0.91	CYP2D6-substrate:	0.689
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

6.393

Half-life (T1/2):

1.958

ADMET: Toxicity

hERG Blockers:	0.128	hERG Blockers (10um):	0.59
Human Hepatotoxicity (H-HT):	0.691	Drug-induced Liver Injury (DILI):	0.528
AMES Toxicity:	0.623	Rat Oral Acute Toxicity:	0.572
Maximum Recommended Daily Dose:	0.578	Skin Sensitization:	0.898
Carcinogencity:	0.56	Eye Corrosion:	0.003
Eye Irritation:	0.89	Respiratory Toxicity:	0.77
Drug-induced Neurotoxicity:	0.567	Ototoxicity:	0.598
Hematotoxicity:	0.294	Drug-induced Nephrotoxicity:	0.605
Genotoxicity:	0.674	RPMI-8226 Immunitoxicity:	0.055
A549 Cytotoxicity:	0.309	Hek293 Cytotoxicity:	0.611
BCF:	2.109 ? 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:	4.908 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.585 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.917 ? 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
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	roots	n.a.	n.a.	PMID[19132934]
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[19132934]
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13293	Lespedeza floribunda	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
IC50	1

Activity Type	# Activity
Others	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
NPT2	Others	Unspecified	n.a.	IC50	=	6160.0	nM	PMID[12502346]

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 NPC476166 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	24028
0.1-0.2	21687
0.2-0.3	3797
0.3-0.4	264
0.4-0.5	38
0.5-0.6	34
0.6-0.7	4
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8197	Intermediate Similarity	NPC228369
0.8197	Intermediate Similarity	NPC300875
0.75	Intermediate Similarity	NPC280653
0.7121	Intermediate Similarity	NPC45257
0.7031	Intermediate Similarity	NPC164574
0.6769	Remote Similarity	NPC150011
0.6615	Remote Similarity	NPC236014
0.6269	Remote Similarity	NPC605244
0.6056	Remote Similarity	NPC47633
0.5942	Remote Similarity	NPC118114
0.5833	Remote Similarity	NPC471215
0.5833	Remote Similarity	NPC12641
0.5833	Remote Similarity	NPC262573
0.5714	Remote Similarity	NPC129784
0.5714	Remote Similarity	NPC206224
0.5692	Remote Similarity	NPC27495
0.5634	Remote Similarity	NPC27187
0.5634	Remote Similarity	NPC470225
0.5606	Remote Similarity	NPC198358
0.5606	Remote Similarity	NPC39064
0.5606	Remote Similarity	NPC73320
0.5606	Remote Similarity	NPC47283
0.5606	Remote Similarity	NPC295697
0.5571	Remote Similarity	NPC196765
0.5522	Remote Similarity	NPC236306
0.5522	Remote Similarity	NPC107161
0.5493	Remote Similarity	NPC12875
0.5429	Remote Similarity	NPC85264
0.5417	Remote Similarity	NPC124085
0.5417	Remote Similarity	NPC271945
0.5405	Remote Similarity	NPC85435
0.5405	Remote Similarity	NPC63879
0.5373	Remote Similarity	NPC129106
0.5278	Remote Similarity	NPC102044
0.527	Remote Similarity	NPC280092
0.527	Remote Similarity	NPC93323
0.527	Remote Similarity	NPC225696
0.5205	Remote Similarity	NPC268917
0.5147	Remote Similarity	NPC32633
0.5135	Remote Similarity	NPC223008
0.5128	Remote Similarity	NPC13005
0.5068	Remote Similarity	NPC62730
0.5067	Remote Similarity	NPC17343

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476166 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3725
0.1-0.2	5311
0.2-0.3	112
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