NPASS Compound

Natural Product: NPC471921

Natural Product ID	NPC471921
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Phyllanthusmins E
IUPAC Name	[(2S,3R,4S,5S)-2-[[9-(1,3-benzodioxol-5-yl)-6,7-dimethoxy-1-oxo-3H-benzo[f][2]benzofuran-4-yl]oxy]-3,5-dihydroxyoxan-4-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3298728
PubChem CID	90683254
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001511] Lignan 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 66 71 0 0 0 0 0 0 0 0999 V2000 0.6559 4.8185 0.7364 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6933 4.4700 0.6809 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1253 3.1824 0.3665 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1784 2.2355 0.1050 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5496 0.9267 -0.2161 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4197 -0.0193 -0.4785 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7659 0.2818 -0.4344 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5785 0.1712 0.7069 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2141 1.3301 1.0778 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9904 1.8852 0.0907 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9087 0.8513 -0.5615 C 0 0 1 0 0 0 0 0 0 0 0 0 4.9759 -0.3146 0.4168 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5766 -0.9356 0.4329 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5034 -1.9646 1.3554 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8868 -1.2806 -0.0650 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0053 -1.6120 0.6768 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1612 -1.0193 1.7768 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0002 -2.6275 0.2125 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2907 0.4198 -1.7325 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0145 -1.3026 -0.7932 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8094 -2.4998 -1.1150 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1652 -3.4901 -1.3419 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4368 -3.0190 -1.1922 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5512 -3.6058 -1.3138 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3243 -1.6064 -0.8378 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2987 -0.6418 -0.5705 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8972 0.6380 -0.2567 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8878 1.5863 0.0062 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4727 2.8636 0.3184 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3848 3.8725 0.5947 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7567 3.5600 0.5488 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7212 -1.0143 -0.6305 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4494 -0.9122 -1.7904 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7823 -1.2598 -1.8525 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3816 -1.7253 -0.6879 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6871 -1.8394 0.4828 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3458 -1.4797 0.5066 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5216 -2.3311 1.5007 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7049 -2.7334 0.8528 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6935 -2.1515 -0.4248 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1223 4.6149 1.7261 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2678 4.4183 -0.0949 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7066 5.9384 0.6237 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8884 2.4258 0.1266 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9626 -0.1833 1.5641 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3984 2.3916 -0.7084 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6156 2.6793 0.5596 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9154 1.2698 -0.7634 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2569 0.1049 1.3871 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4457 -1.3900 -0.5706 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9745 -2.7482 0.9470 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8824 -2.5679 0.8633 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4906 -3.6120 0.2587 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2335 -2.4366 -0.8525 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9621 0.4127 -2.4712 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3599 -2.7891 -0.1965 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4808 -2.3534 -1.9826 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9324 1.3105 -0.0383 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0001 3.1913 -0.4731 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9175 2.6893 1.2395 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3906 4.4047 0.8525 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9697 -0.5486 -2.6879 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3675 -1.1835 -2.7621 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8055 -1.5750 1.4426 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7753 -3.8323 0.7747 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5530 -2.3389 1.4663 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 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 12 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 11 19 1 0 6 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 26 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 36 38 1 0 38 39 1 0 39 40 1 0 29 3 1 0 37 32 1 0 27 5 1 0 40 35 1 0 13 8 1 0 25 20 2 0 1 41 1 0 1 42 1 0 1 43 1 0 4 44 1 0 8 45 1 1 10 46 1 0 10 47 1 0 11 48 1 6 12 49 1 1 13 50 1 6 14 51 1 0 18 52 1 0 18 53 1 0 18 54 1 0 19 55 1 0 21 56 1 0 21 57 1 0 28 58 1 0 31 59 1 0 31 60 1 0 31 61 1 0 33 62 1 0 34 63 1 0 37 64 1 0 39 65 1 0 39 66 1 0 M END

Standard InCHIKey	WKELRQBASNTBAF-RHYPXFPASA-N
Standard InCHI	InChI=1S/C28H26O12/c1-12(29)39-26-17(30)10-36-28(24(26)31)40-25-15-8-20(34-3)19(33-2)7-14(15)22(23-16(25)9-35-27(23)32)13-4-5-18-21(6-13)38-11-37-18/h4-8,17,24,26,28,30-31H,9-11H2,1-3H3/t17-,24+,26-,28-/m0/s1
SMILES	COc1cc2c(O[C@@H]3OC[C@@H]([C@@H]([C@H]3O)OC(=O)C)O)c3COC(=O)c3c(c2cc1OC)c1ccc2c(c1)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	554.14	Volume:	520.623 ? Van der Waals volume.
Dense:	1.064	LogP:	1.791 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.057 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.506 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	33.0
TPSA:	148.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.431	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.114	Fsp³:	0.357
MCE-18:	117.895 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.914	Fluc inhibitor:	0.2 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.738 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.483 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.024	Promiscuous compounds:	0.55

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.88	MDCK Permeability:	-5.065
Pgp-inhibitor:	0.167	Pgp-substrate:	0.438
PAMPA:	0.829 ? 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):	0.012
20% Bioavailability (F20%):	0.038	30% Bioavailability (F30%):	0.004
50% Bioavailability (F50%):	0.839

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.018	MRP1:	0.847
Plasma Protein Binding (PPB):	95.382%	Volume Distribution (VD):	-0.072
Fu:	5.541% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.166
BSEP inhibitor:	0.975

ADMET: Metabolism

CYP1A2-inhibitor:	0.066	CYP1A2-substrate:	0.015
CYP2C19-inhibitor:	0.437	CYP2C19-substrate:	0.012
CYP2C9-inhibitor:	0.685	CYP2C9-substrate:	0.59
CYP2D6-inhibitor:	0.118	CYP2D6-substrate:	0.926
CYP3A4-inhibitor:	0.034	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.649
HLM stability:	0.31 ? 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):

3.257

Half-life (T1/2):

2.109

ADMET: Toxicity

hERG Blockers:	0.074	hERG Blockers (10um):	0.426
Human Hepatotoxicity (H-HT):	0.944	Drug-induced Liver Injury (DILI):	0.997
AMES Toxicity:	0.966	Rat Oral Acute Toxicity:	0.221
Maximum Recommended Daily Dose:	0.612	Skin Sensitization:	1.0
Carcinogencity:	0.927	Eye Corrosion:	0.0
Eye Irritation:	0.019	Respiratory Toxicity:	0.054
Drug-induced Neurotoxicity:	0.594	Ototoxicity:	0.877
Hematotoxicity:	0.972	Drug-induced Nephrotoxicity:	0.99
Genotoxicity:	0.988	RPMI-8226 Immunitoxicity:	0.381
A549 Cytotoxicity:	0.804	Hek293 Cytotoxicity:	0.793
BCF:	0.931 ? 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:	3.616 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.479 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.568 ? 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
NPO33442	phyllanthus poilanei	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	PMID[24937209]

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
Cell line	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
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	1800.0	nM	PMID[17242150]

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 NPC471921 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	14087
0.1-0.2	34750
0.2-0.3	967
0.3-0.4	16
0.4-0.5	12
0.5-0.6	5
0.6-0.7	11
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
0.7857	Intermediate Similarity	NPC471920
0.759	Intermediate Similarity	NPC20114
0.7529	Intermediate Similarity	NPC292712
0.7529	Intermediate Similarity	NPC471922
0.7439	Intermediate Similarity	NPC474075
0.7439	Intermediate Similarity	NPC483381
0.7143	Intermediate Similarity	NPC184624
0.7059	Intermediate Similarity	NPC114550
0.7059	Intermediate Similarity	NPC312006
0.7059	Intermediate Similarity	NPC602979
0.686	Remote Similarity	NPC473531
0.6818	Remote Similarity	NPC471923
0.6782	Remote Similarity	NPC129930
0.6667	Remote Similarity	NPC239113
0.6566	Remote Similarity	NPC161609
0.6447	Remote Similarity	NPC19600
0.6316	Remote Similarity	NPC473697
0.6026	Remote Similarity	NPC115123
0.602	Remote Similarity	NPC35266
0.602	Remote Similarity	NPC167045
0.602	Remote Similarity	NPC114120
0.5981	Remote Similarity	NPC286301
0.5981	Remote Similarity	NPC313063
0.59	Remote Similarity	NPC275690
0.5556	Remote Similarity	NPC78944
0.5366	Remote Similarity	NPC15212

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471921 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4388
0.1-0.2	4734
0.2-0.3	28
0.3-0.4	0
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