NPASS Compound

Natural Product: NPC471922

Natural Product ID	NPC471922
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Phyllanthusmin B
IUPAC Name	[(3S,4R,5R,6S)-6-[[9-(1,3-benzodioxol-5-yl)-6,7-dimethoxy-1-oxo-3H-benzo[f][2]benzofuran-4-yl]oxy]-4,5-dihydroxyoxan-3-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3298729
PubChem CID	90683255
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 6.3636 -1.9519 3.7343 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3575 -1.6763 2.2649 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3502 -1.9447 1.5469 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2588 -1.1190 1.6364 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2303 -0.8497 0.2560 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2450 -1.6324 -0.5059 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3440 -0.8801 -1.1447 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7487 0.1841 -0.5388 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7430 1.1342 0.0739 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1475 0.5964 -0.0527 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0310 1.2939 0.7645 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4542 1.2683 1.4171 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7653 -0.2783 0.3655 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4284 -0.4149 -0.0241 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0133 -1.7072 -0.4011 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7216 -2.9835 -0.4724 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2423 -3.9056 -0.8996 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4606 -3.3018 -1.1175 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5402 -3.8149 -1.5132 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2881 -1.8858 -0.7930 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2202 -0.8600 -0.8418 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7989 0.4139 -0.4685 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6599 1.4811 -0.5270 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1976 2.7255 -0.1855 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8886 2.9719 0.2233 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0420 1.8913 0.2781 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4839 0.6089 -0.0661 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4807 4.2256 0.5509 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7954 4.5259 1.0050 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0736 3.8059 -0.2477 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4089 3.7098 -0.6343 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5892 -1.0555 -1.2543 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5378 -1.3735 -0.3239 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8447 -1.5565 -0.7452 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1950 -1.4250 -2.0671 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2338 -1.1022 -3.0152 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9425 -0.9212 -2.5969 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5655 -1.6662 -2.1911 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1334 -1.8441 -0.9251 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0188 -1.8805 -0.0484 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2873 -2.4992 3.9848 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4927 -2.5487 4.0367 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3496 -1.0247 4.3159 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2584 -1.1822 -0.1177 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7211 -2.3373 -1.2508 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6707 -2.3007 0.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2060 0.7179 -1.3476 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7183 2.1299 -0.3833 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5362 0.7374 -1.1018 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7586 2.2449 0.7386 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4819 2.1858 1.7503 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6104 -2.9701 -1.1334 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0034 -3.2783 0.5714 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6916 1.2996 -0.8440 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9799 2.0138 0.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0940 3.9274 1.8971 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5194 4.3992 0.1767 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9000 5.5971 1.3220 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5443 3.4434 -1.6996 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9527 2.8933 -0.0744 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9315 4.6890 -0.4539 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3299 -1.4894 0.7381 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5276 -1.0010 -4.0625 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2055 -0.6686 -3.3575 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8246 -0.9980 -0.6443 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7317 -2.7868 -0.8960 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 9 12 1 0 8 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 25 28 1 0 28 29 1 0 24 30 1 0 30 31 1 0 21 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 35 38 1 0 38 39 1 0 39 40 1 0 10 5 1 0 27 14 1 0 20 15 1 0 27 22 1 0 37 32 1 0 40 34 1 0 1 41 1 0 1 42 1 0 1 43 1 0 5 44 1 0 6 45 1 0 6 46 1 0 8 47 1 0 9 48 1 0 10 49 1 0 11 50 1 0 12 51 1 0 16 52 1 0 16 53 1 0 23 54 1 0 26 55 1 0 29 56 1 0 29 57 1 0 29 58 1 0 31 59 1 0 31 60 1 0 31 61 1 0 33 62 1 0 36 63 1 0 37 64 1 0 39 65 1 0 39 66 1 0 M END

Standard InCHIKey	PDCZTHZYQGOSBV-WVZMWUMTSA-N
Standard InCHI	InChI=1S/C28H26O12/c1-12(29)39-21-10-36-28(25(31)24(21)30)40-26-15-8-19(34-3)18(33-2)7-14(15)22(23-16(26)9-35-27(23)32)13-4-5-17-20(6-13)38-11-37-17/h4-8,21,24-25,28,30-31H,9-11H2,1-3H3/t21-,24-,25+,28-/m0/s1
SMILES	CC(=O)OC1COC(C(C1O)O)OC2=C3COC(=O)C3=C(C4=CC(=C(C=C42)OC)OC)C5=CC6=C(C=C5)OCO6

Calculated Properties

Physi-Chem Properties

Molecular Weight:	554.14	Volume:	520.623 ? Van der Waals volume.
Dense:	1.064	LogP:	2.145 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.264 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.69 ? 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:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.11	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:	0.584	Fluc inhibitor:	0.013 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.757 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.728 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.018	Promiscuous compounds:	0.102

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.837	MDCK Permeability:	-5.036
Pgp-inhibitor:	0.013	Pgp-substrate:	0.305
PAMPA:	0.91 ? 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):	0.088
20% Bioavailability (F20%):	0.146	30% Bioavailability (F30%):	0.005
50% Bioavailability (F50%):	0.943

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.035	MRP1:	0.93
Plasma Protein Binding (PPB):	96.429%	Volume Distribution (VD):	-0.105
Fu:	4.332% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.915
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.276
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.224	CYP1A2-substrate:	0.005
CYP2C19-inhibitor:	0.935	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.835	CYP2C9-substrate:	0.292
CYP2D6-inhibitor:	0.593	CYP2D6-substrate:	0.664
CYP3A4-inhibitor:	0.055	CYP3A4-substrate:	0.157
CYP2B6-substrate:	0.224	CYP2C8-inhibitor:	0.104
HLM stability:	0.088 ? 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):

2.175

Half-life (T1/2):

1.712

ADMET: Toxicity

hERG Blockers:	0.139	hERG Blockers (10um):	0.575
Human Hepatotoxicity (H-HT):	0.888	Drug-induced Liver Injury (DILI):	0.987
AMES Toxicity:	0.91	Rat Oral Acute Toxicity:	0.556
Maximum Recommended Daily Dose:	0.909	Skin Sensitization:	0.939
Carcinogencity:	0.936	Eye Corrosion:	0.0
Eye Irritation:	0.004	Respiratory Toxicity:	0.069
Drug-induced Neurotoxicity:	0.801	Ototoxicity:	0.945
Hematotoxicity:	0.873	Drug-induced Nephrotoxicity:	0.933
Genotoxicity:	0.943	RPMI-8226 Immunitoxicity:	0.345
A549 Cytotoxicity:	0.464	Hek293 Cytotoxicity:	0.859
BCF:	0.969 ? 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:	3.531 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.895 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.621 ? 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 NPC471922 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	15436
0.1-0.2	32764
0.2-0.3	1601
0.3-0.4	18
0.4-0.5	12
0.5-0.6	6
0.6-0.7	10
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	NPC292712
0.7765	Intermediate Similarity	NPC471920
0.7561	Intermediate Similarity	NPC474075
0.7561	Intermediate Similarity	NPC483381
0.7529	Intermediate Similarity	NPC471921
0.75	Intermediate Similarity	NPC20114
0.7381	Intermediate Similarity	NPC114550
0.7381	Intermediate Similarity	NPC312006
0.7381	Intermediate Similarity	NPC602979
0.7093	Intermediate Similarity	NPC129930
0.7059	Intermediate Similarity	NPC184624
0.6932	Remote Similarity	NPC471923
0.6782	Remote Similarity	NPC473531
0.6667	Remote Similarity	NPC161609
0.6579	Remote Similarity	NPC239113
0.6421	Remote Similarity	NPC473697
0.6364	Remote Similarity	NPC19600
0.6327	Remote Similarity	NPC275690
0.6122	Remote Similarity	NPC35266
0.6122	Remote Similarity	NPC167045
0.6122	Remote Similarity	NPC114120
0.5949	Remote Similarity	NPC115123
0.5488	Remote Similarity	NPC78944
0.5357	Remote Similarity	NPC286301
0.5357	Remote Similarity	NPC313063
0.5301	Remote Similarity	NPC15212
0.5053	Remote Similarity	NPC474442

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471922 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4564
0.1-0.2	4548
0.2-0.3	38
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