NPASS Compound

Natural Product: NPC159720

Natural Product ID	NPC159720
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IIWKLAHNKXXKAJ-WAABAYLZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	46186857
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001844] Flavonolignans

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 61 0 0 0 0 0 0 0 0999 V2000 -9.1244 1.2442 0.3687 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2560 0.1831 0.0300 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8838 0.3842 0.0711 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3831 1.6026 0.4375 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0322 1.8310 0.4873 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1550 0.8156 0.1625 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6631 -0.4086 -0.2056 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9997 -0.6265 -0.2524 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5521 -1.8623 -0.6233 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6873 1.0623 0.2161 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1408 0.3023 1.3841 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8361 0.7416 2.6392 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4324 0.0065 3.7510 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7359 0.4415 1.4661 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0128 0.2155 0.3038 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3246 -0.0476 0.2520 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0196 -0.2689 -0.9201 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3067 -0.2180 -2.1000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0483 0.0439 -2.1091 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6951 0.2587 -0.8990 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0698 0.5205 -0.9613 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4690 -0.5509 -0.9324 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8041 -1.9745 -0.5974 C 0 0 2 0 0 0 0 0 0 0 0 0 5.2777 -2.1374 -0.8026 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7951 -3.1451 -1.3077 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1794 -1.0430 -0.3842 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5443 -1.2206 -0.3495 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3607 -0.1823 0.0449 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7908 1.0238 0.3999 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4206 1.1785 0.3573 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5718 0.1479 -0.0367 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1885 0.3264 -0.0724 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6352 2.0444 0.7903 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0892 -2.4438 -0.7117 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1723 -2.8025 -1.5175 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0179 1.4756 1.4396 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1733 0.9448 0.1438 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8479 2.1168 -0.2640 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0633 2.4193 0.6983 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6339 2.7953 0.7772 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9815 -1.2105 -0.4619 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6324 -2.0430 -1.6099 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5134 2.1371 0.2379 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3404 -0.7750 1.2078 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7265 1.8166 2.8122 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9190 0.5368 2.5050 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2304 -0.9271 3.5259 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8758 -0.0840 1.2042 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7990 -0.3853 -3.0725 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6059 0.0838 -3.0311 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8472 -0.3482 -1.9557 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5501 -2.2422 0.4494 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4537 -0.3150 0.0758 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9565 2.1317 0.6369 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1057 2.6669 0.1423 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1576 -2.6840 -1.7020 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6985 -3.5533 -1.0882 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 6 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 11 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 17 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 29 33 1 0 27 34 1 0 23 35 1 0 8 3 1 0 21 10 1 0 32 22 1 0 20 15 1 0 31 26 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 5 40 1 0 7 41 1 0 9 42 1 0 10 43 1 1 11 44 1 6 12 45 1 0 12 46 1 0 13 47 1 0 16 48 1 0 18 49 1 0 19 50 1 0 22 51 1 6 23 52 1 1 28 53 1 0 30 54 1 0 33 55 1 0 34 56 1 0 35 57 1 0 M END

Standard InCHIKey	IIWKLAHNKXXKAJ-WAABAYLZSA-N
Standard InCHI	InChI=1S/C25H22O10/c1-32-16-4-2-11(6-14(16)28)24-20(10-26)33-18-7-12(3-5-17(18)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3/t20-,23-,24-,25+/m0/s1
SMILES	COc1ccc(cc1O)[C@H]1[C@H](CO)Oc2cc(ccc2O1)[C@@H]1[C@H](C(=O)c2c(cc(cc2O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	482.12	Volume:	459.711 ? Van der Waals volume.
Dense:	1.049	LogP:	1.926 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.099 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.036 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	29.0
TPSA:	155.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	5.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.374	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.006	Fsp³:	0.24
MCE-18:	97.742 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.833	Fluc inhibitor:	0.547 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.056 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.565 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.38	Promiscuous compounds:	0.344

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.477	MDCK Permeability:	-5.27
Pgp-inhibitor:	0.994	Pgp-substrate:	0.105
PAMPA:	0.055 ? 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):	0.003
20% Bioavailability (F20%):	0.003	30% Bioavailability (F30%):	0.959
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012	MRP1:	0.762
Plasma Protein Binding (PPB):	95.464%	Volume Distribution (VD):	0.036
Fu:	3.94% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.976
BSEP inhibitor:	0.962

ADMET: Metabolism

CYP1A2-inhibitor:	0.806	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.199	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.013	CYP2D6-substrate:	0.614
CYP3A4-inhibitor:	0.151	CYP3A4-substrate:	0.911
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.942
HLM stability:	0.009 ? 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):

4.035

Half-life (T1/2):

2.411

ADMET: Toxicity

hERG Blockers:	0.121	hERG Blockers (10um):	0.366
Human Hepatotoxicity (H-HT):	0.925	Drug-induced Liver Injury (DILI):	0.921
AMES Toxicity:	0.78	Rat Oral Acute Toxicity:	0.55
Maximum Recommended Daily Dose:	0.289	Skin Sensitization:	0.996
Carcinogencity:	0.405	Eye Corrosion:	0.0
Eye Irritation:	0.848	Respiratory Toxicity:	0.564
Drug-induced Neurotoxicity:	0.397	Ototoxicity:	0.634
Hematotoxicity:	0.44	Drug-induced Nephrotoxicity:	0.92
Genotoxicity:	0.978	RPMI-8226 Immunitoxicity:	0.324
A549 Cytotoxicity:	0.907	Hek293 Cytotoxicity:	0.811
BCF:	0.877 ? 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:	3.542 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.058 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.218 ? 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
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1080/10496475.2013.791908]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	whole plant	n.a.	PMID[16394559]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24456525]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	Seeds	n.a.	n.a.	PMID[24597776]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5645	Silybum marianum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5645	Silybum marianum	Species	Asteraceae	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 NPC159720 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	24789
0.1-0.2	21179
0.2-0.3	3467
0.3-0.4	322
0.4-0.5	65
0.5-0.6	22
0.6-0.7	3
0.7-0.8	3
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8286	Intermediate Similarity	NPC138688
0.8286	Intermediate Similarity	NPC72787
0.8286	Intermediate Similarity	NPC217795
0.8286	Intermediate Similarity	NPC58223
0.7887	Intermediate Similarity	NPC36916
0.7887	Intermediate Similarity	NPC36
0.7887	Intermediate Similarity	NPC7154
0.7887	Intermediate Similarity	NPC125039
0.7887	Intermediate Similarity	NPC7688
0.746	Intermediate Similarity	NPC320825
0.6232	Remote Similarity	NPC326037
0.6232	Remote Similarity	NPC13858
0.6119	Remote Similarity	NPC250922
0.597	Remote Similarity	NPC44721
0.597	Remote Similarity	NPC211466
0.597	Remote Similarity	NPC605332
0.5882	Remote Similarity	NPC36835
0.5882	Remote Similarity	NPC246162
0.5882	Remote Similarity	NPC9743
0.5882	Remote Similarity	NPC260491
0.5882	Remote Similarity	NPC61506
0.5882	Remote Similarity	NPC240476
0.5714	Remote Similarity	NPC471515
0.5588	Remote Similarity	NPC19721
0.5522	Remote Similarity	NPC21835
0.5441	Remote Similarity	NPC62290
0.5441	Remote Similarity	NPC142731
0.5441	Remote Similarity	NPC326506
0.5441	Remote Similarity	NPC4152
0.5357	Remote Similarity	NPC279209
0.5357	Remote Similarity	NPC102277
0.5357	Remote Similarity	NPC479117
0.5294	Remote Similarity	NPC75827
0.5139	Remote Similarity	NPC302950
0.506	Remote Similarity	NPC606364

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC159720 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5193
0.1-0.2	3868
0.2-0.3	80
0.3-0.4	5
0.4-0.5	0
0.5-0.6	1
0.6-0.7	0
0.7-0.8	3
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
0.7887	Intermediate Similarity	NPD6166	Phase 2
0.7887	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7887	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.5139	Remote Similarity	NPD1934	Phase 0

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