NPASS Compound

Natural Product: NPC319209

Natural Product ID	NPC319209
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HLBPOYVRLSXWJJ-WICREQFHSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5320458
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan lactones

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 52 56 0 0 0 0 0 0 0 0999 V2000 3.1563 -0.1782 -3.5943 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6986 0.4429 -2.4458 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9476 0.3885 -1.2760 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7219 -0.2390 -1.2122 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9551 -0.3033 -0.0476 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4966 0.3052 1.0594 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7386 0.9501 1.0254 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4508 0.9825 -0.1499 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6884 1.6154 -0.2167 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8964 0.8963 0.0554 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2783 1.5596 2.1388 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6035 1.5705 3.3947 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3285 -0.9841 -0.0483 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7009 -1.6704 1.2427 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7172 -2.7621 0.8454 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9170 -2.1904 0.1476 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7228 -0.8222 -0.3808 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8466 -0.1321 -0.7836 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7682 1.1562 -1.2933 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5316 1.7620 -1.3993 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4034 1.0525 -0.9881 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4896 -0.2191 -0.4861 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7455 3.0269 -1.9320 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1256 3.3412 -1.9195 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7157 2.0729 -1.7676 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1186 -0.7049 -0.6948 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1938 -3.1259 2.2623 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3088 -1.8400 2.8390 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5770 -0.8971 2.1277 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7218 0.3353 2.2929 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8028 0.0348 -4.4478 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0558 -1.2749 -3.3894 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1321 0.2356 -3.7499 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3254 -0.7114 -2.1146 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9874 0.3052 1.9876 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7034 -0.1815 0.1587 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6465 1.1108 -0.7328 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2559 1.2835 1.0352 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6701 0.6131 3.9145 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5402 1.8751 3.1660 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9912 2.3802 4.0464 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2270 -1.8298 -0.8003 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1434 -2.1592 1.7198 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2361 -3.5928 0.3355 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1190 -2.8487 -0.7436 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8372 -2.1785 0.7651 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4575 1.5774 -1.0939 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4603 3.7705 -2.8942 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3752 4.0226 -1.0651 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7166 -0.4975 0.0702 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3882 -3.6491 2.8173 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1366 -3.6748 2.2200 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 9 10 1 0 7 11 1 0 11 12 1 0 5 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 20 23 1 0 23 24 1 0 24 25 1 0 18 26 1 0 15 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 8 3 1 0 22 13 1 0 29 14 1 0 22 17 1 0 25 19 1 0 1 31 1 0 1 32 1 0 1 33 1 0 4 34 1 0 6 35 1 0 10 36 1 0 10 37 1 0 10 38 1 0 12 39 1 0 12 40 1 0 12 41 1 0 13 42 1 0 14 43 1 0 15 44 1 0 16 45 1 0 16 46 1 0 21 47 1 0 24 48 1 0 24 49 1 0 26 50 1 0 27 51 1 0 27 52 1 0 M END

Standard InCHIKey	HLBPOYVRLSXWJJ-WICREQFHSA-N
Standard InCHI	InChI=1S/C22H22O8/c1-25-14-5-10(6-15(26-2)20(14)27-3)17-12-7-16-21(30-9-29-16)19(23)13(12)4-11-8-28-22(24)18(11)17/h5-7,11,17-18,23H,4,8-9H2,1-3H3/t11?,17?,18-/m0/s1
SMILES	COC1=CC(=CC(=C1OC)OC)C2C3C(CC4=C(C5=C(C=C24)OCO5)O)COC3=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	414.13	Volume:	398.152 ? Van der Waals volume.
Dense:	1.04	LogP:	2.045 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.323 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.39 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	26.0
TPSA:	92.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.764	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.784	Fsp³:	0.409
MCE-18:	94.839 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.125	Fluc inhibitor:	0.015 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.371 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.517 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.081	Promiscuous compounds:	0.103

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.099	MDCK Permeability:	-4.767
Pgp-inhibitor:	0.047	Pgp-substrate:	0.003
PAMPA:	0.169 ? 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):	0.0
20% Bioavailability (F20%):	0.028	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.569

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.941	MRP1:	0.997
Plasma Protein Binding (PPB):	98.655%	Volume Distribution (VD):	-0.374
Fu:	1.4% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.608
OATP1B3 inhibitor:	0.952	BCRP inhibitor:	0.014
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.422	CYP1A2-substrate:	0.789
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.559	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.982
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.918
CYP2B6-substrate:	0.004	CYP2C8-inhibitor:	0.39
HLM stability:	0.461 ? 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):

4.208

Half-life (T1/2):

1.72

ADMET: Toxicity

hERG Blockers:	0.169	hERG Blockers (10um):	0.696
Human Hepatotoxicity (H-HT):	0.836	Drug-induced Liver Injury (DILI):	0.963
AMES Toxicity:	0.441	Rat Oral Acute Toxicity:	0.418
Maximum Recommended Daily Dose:	0.896	Skin Sensitization:	0.473
Carcinogencity:	0.923	Eye Corrosion:	0.0
Eye Irritation:	0.176	Respiratory Toxicity:	0.7
Drug-induced Neurotoxicity:	0.738	Ototoxicity:	0.909
Hematotoxicity:	0.615	Drug-induced Nephrotoxicity:	0.844
Genotoxicity:	0.78	RPMI-8226 Immunitoxicity:	0.189
A549 Cytotoxicity:	0.448	Hek293 Cytotoxicity:	0.515
BCF:	1.454 ? 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:	3.914 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.738 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.771 ? 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
NPO23848	Podophyllum peltatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16933860]
NPO23848	Podophyllum peltatum	Species	Berberidaceae	Eukaryota	n.a.	root	n.a.	Database[Article]
NPO23848	Podophyllum peltatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3158	Linum album	Species	Linaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23848	Podophyllum peltatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3158	Linum album	Species	Linaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3158	Linum album	Species	Linaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23848	Podophyllum peltatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3158	Linum album	Species	Linaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23848	Podophyllum peltatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO3158	Linum album	Species	Linaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23848	Podophyllum peltatum	Species	Berberidaceae	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 NPC319209 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	22325
0.1-0.2	25614
0.2-0.3	1687
0.3-0.4	152
0.4-0.5	52
0.5-0.6	15
0.6-0.7	11
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC115281
0.8548	High Similarity	NPC163527
0.6984	Remote Similarity	NPC80230
0.6984	Remote Similarity	NPC104024
0.6984	Remote Similarity	NPC101755
0.6984	Remote Similarity	NPC304687
0.6984	Remote Similarity	NPC65574
0.6769	Remote Similarity	NPC149505
0.6615	Remote Similarity	NPC262455
0.6615	Remote Similarity	NPC177476
0.6515	Remote Similarity	NPC480477
0.6324	Remote Similarity	NPC30009
0.6324	Remote Similarity	NPC103197
0.5588	Remote Similarity	NPC218092
0.5588	Remote Similarity	NPC239890
0.5588	Remote Similarity	NPC209411
0.5588	Remote Similarity	NPC246474
0.5588	Remote Similarity	NPC162851
0.5571	Remote Similarity	NPC237946
0.5571	Remote Similarity	NPC32373
0.5417	Remote Similarity	NPC207584
0.5417	Remote Similarity	NPC19947
0.5294	Remote Similarity	NPC222531
0.5238	Remote Similarity	NPC115624
0.5205	Remote Similarity	NPC210642
0.5205	Remote Similarity	NPC13985
0.5147	Remote Similarity	NPC477698
0.5067	Remote Similarity	NPC119910

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC319209 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4907
0.1-0.2	4172
0.2-0.3	59
0.3-0.4	6
0.4-0.5	3
0.5-0.6	3
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
0.5571	Remote Similarity	NPD4965	Approved
0.5571	Remote Similarity	NPD4966	Phase 4
0.5571	Remote Similarity	NPD4967	Phase 2

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