NPASS Compound

Natural Product: NPC471920

Natural Product ID	NPC471920
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Phyllanthusmins D
IUPAC Name	[(3S,4R,5R,6S)-4-acetyloxy-6-[[9-(1,3-benzodioxol-5-yl)-6,7-dimethoxy-1-oxo-3H-benzo[f][2]benzofuran-4-yl]oxy]-5-hydroxyoxan-3-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3298727
PubChem CID	90683253
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 71 76 0 0 0 0 0 0 0 0999 V2000 -0.1844 -4.1532 -1.9866 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4527 -3.5847 -1.9001 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7829 -2.4475 -1.1780 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7900 -1.7788 -0.4565 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1113 -0.6407 0.2668 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1417 0.0208 0.9886 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1823 -0.3961 1.0233 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1964 0.0443 0.1441 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6609 -1.0656 -0.5610 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4669 -0.7007 -1.6386 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4755 0.3439 -1.2229 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6892 0.1691 0.2620 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3812 0.5480 0.9416 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4092 1.9117 1.1145 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0014 -1.1730 0.5824 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1911 -1.5304 1.1891 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0118 -0.6116 1.4587 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5794 -2.9154 1.5501 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6630 0.2070 -1.9742 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1585 1.2263 -2.7822 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4820 2.2972 -2.8108 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4165 1.0912 -3.5815 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5303 1.1448 1.6990 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2564 2.0871 2.5605 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6931 3.0055 3.0332 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9501 2.7733 2.5340 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0229 3.4012 2.7186 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8310 1.5709 1.6758 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8113 0.9171 0.9554 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4244 -0.2059 0.2454 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4000 -0.8838 -0.4782 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0884 -2.0161 -1.1999 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0039 -2.7436 -1.9432 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3652 -2.3987 -2.0463 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1860 1.3953 0.9469 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6205 2.3021 0.0147 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9334 2.7680 -0.0099 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8515 2.3077 0.9397 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4104 1.3950 1.8767 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1005 0.9462 1.8808 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5192 1.1311 2.6655 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5113 2.1198 2.4487 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1912 2.5876 1.1544 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2894 -4.3385 -0.9948 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5146 -3.5971 -2.6599 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3033 -5.1578 -2.4903 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2156 -2.1656 -0.4704 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7443 0.8003 -0.5180 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8206 -0.3665 -2.4612 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0206 -1.6074 -1.9984 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0761 1.3545 -1.4133 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5366 0.8002 0.5824 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3093 0.0719 1.9510 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1067 2.3536 0.5649 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0512 -3.6870 0.9517 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3875 -3.0603 2.6362 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6778 -3.0838 1.4153 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1936 0.5419 -3.0282 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1997 0.6574 -4.5770 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7908 2.1297 -3.7764 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7948 1.5698 3.3555 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9078 2.6606 1.8584 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4157 -0.5271 -0.4792 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0030 -3.2698 -2.3025 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4492 -1.6850 -2.8881 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7684 -1.8958 -1.1486 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9576 2.6936 -0.7418 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2593 3.4902 -0.7617 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7829 0.2180 2.6406 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4741 2.9339 3.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5373 1.6998 2.4616 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 19 20 1 0 20 21 2 0 20 22 1 0 6 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 1 0 29 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 39 41 1 0 41 42 1 0 42 43 1 0 32 3 1 0 40 35 1 0 30 5 1 0 43 38 1 0 13 8 1 0 28 23 2 0 1 44 1 0 1 45 1 0 1 46 1 0 4 47 1 0 8 48 1 6 10 49 1 0 10 50 1 0 11 51 1 1 12 52 1 1 13 53 1 1 14 54 1 0 18 55 1 0 18 56 1 0 18 57 1 0 22 58 1 0 22 59 1 0 22 60 1 0 24 61 1 0 24 62 1 0 31 63 1 0 34 64 1 0 34 65 1 0 34 66 1 0 36 67 1 0 37 68 1 0 40 69 1 0 42 70 1 0 42 71 1 0 M END

Standard InCHIKey	LMBQTGJDJLTHRF-ZCDCQGGYSA-N
Standard InCHI	InChI=1S/C30H28O13/c1-13(31)41-23-11-38-30(26(33)28(23)42-14(2)32)43-27-17-9-21(36-4)20(35-3)8-16(17)24(25-18(27)10-37-29(25)34)15-5-6-19-22(7-15)40-12-39-19/h5-9,23,26,28,30,33H,10-12H2,1-4H3/t23-,26+,28-,30-/m0/s1
SMILES	COc1cc2c(O[C@@H]3OC[C@@H]([C@@H]([C@H]3O)OC(=O)C)OC(=O)C)c3COC(=O)c3c(c2cc1OC)c1ccc2c(c1)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	596.15	Volume:	561.369 ? Van der Waals volume.
Dense:	1.062	LogP:	2.038 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.236 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.643 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	34.0
TPSA:	154.51 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.314	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.192	Fsp³:	0.367
MCE-18:	120.293 ? 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:	0.972	Fluc inhibitor:	0.106 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.722 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.456 ? 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:	-5.573	MDCK Permeability:	-4.843
Pgp-inhibitor:	0.555	Pgp-substrate:	0.188
PAMPA:	0.696 ? 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):	0.03
20% Bioavailability (F20%):	0.076	30% Bioavailability (F30%):	0.009
50% Bioavailability (F50%):	0.912

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.953
Plasma Protein Binding (PPB):	97.162%	Volume Distribution (VD):	-0.208
Fu:	3.279% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.193
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.365	CYP1A2-substrate:	0.052
CYP2C19-inhibitor:	0.749	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.407	CYP2C9-substrate:	0.834
CYP2D6-inhibitor:	0.082	CYP2D6-substrate:	0.867
CYP3A4-inhibitor:	0.197	CYP3A4-substrate:	0.817
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.91
HLM stability:	0.683 ? 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):

3.719

Half-life (T1/2):

1.296

ADMET: Toxicity

hERG Blockers:	0.063	hERG Blockers (10um):	0.373
Human Hepatotoxicity (H-HT):	0.965	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.981	Rat Oral Acute Toxicity:	0.325
Maximum Recommended Daily Dose:	0.608	Skin Sensitization:	1.0
Carcinogencity:	0.962	Eye Corrosion:	0.0
Eye Irritation:	0.012	Respiratory Toxicity:	0.024
Drug-induced Neurotoxicity:	0.66	Ototoxicity:	0.764
Hematotoxicity:	0.973	Drug-induced Nephrotoxicity:	0.987
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.339
A549 Cytotoxicity:	0.788	Hek293 Cytotoxicity:	0.756
BCF:	0.895 ? 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:	3.656 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.487 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.714 ? 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
Activity	9
IC50	1

Activity Type	# Activity
Individual protein	1
Cell line	9

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1044	Individual protein	DNA topoisomerase II alpha	Homo sapiens	Activity	=	2.8	%	PMID[16441070]

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	=	170.0	nM	PMID[17242150]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	5.51	%	PMID[26042639]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	7.01	%	PMID[21658963]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	26.1	%	PMID[15787444]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	27.3	%	PMID[15787444]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	28.2	%	PMID[15787444]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	30.3	%	PMID[16949283]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	37.5	%	PMID[23268606]
NPT139	Cell line	HT-29	Homo sapiens	Activity	=	38.0	%	PMID[10924160]

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 NPC471920 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	15888
0.1-0.2	32951
0.2-0.3	967
0.3-0.4	15
0.4-0.5	10
0.5-0.6	8
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8734	High Similarity	NPC20114
0.7857	Intermediate Similarity	NPC471921
0.7765	Intermediate Similarity	NPC471922
0.7558	Intermediate Similarity	NPC292712
0.7474	Intermediate Similarity	NPC161609
0.7442	Intermediate Similarity	NPC471923
0.7059	Intermediate Similarity	NPC474075
0.7059	Intermediate Similarity	NPC483381
0.6977	Remote Similarity	NPC184624
0.6897	Remote Similarity	NPC114550
0.6897	Remote Similarity	NPC312006
0.6897	Remote Similarity	NPC602979
0.6882	Remote Similarity	NPC473697
0.6705	Remote Similarity	NPC473531
0.6629	Remote Similarity	NPC129930
0.6494	Remote Similarity	NPC239113
0.6282	Remote Similarity	NPC19600
0.6263	Remote Similarity	NPC275690
0.59	Remote Similarity	NPC35266
0.59	Remote Similarity	NPC167045
0.59	Remote Similarity	NPC114120
0.5875	Remote Similarity	NPC115123
0.5422	Remote Similarity	NPC78944
0.531	Remote Similarity	NPC286301
0.531	Remote Similarity	NPC313063
0.5238	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 NPC471920 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4680
0.1-0.2	4446
0.2-0.3	23
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