NPASS Compound

Natural Product: NPC228469

Natural Product ID	NPC228469
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JPDORDSJPIKURD-UAFHBQARSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	10088741
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003423] 7,7'-epoxylignans

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 47 50 0 0 0 0 0 0 0 0999 V2000 1.5284 2.1087 -1.4028 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2515 2.0932 -0.6108 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7453 1.0791 -1.1302 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6239 1.6350 -2.2231 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5273 0.8328 0.1573 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4059 -0.3433 0.0516 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9535 -1.6278 -0.0977 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8532 -2.6694 -0.1890 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2183 -2.4623 -0.1344 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6868 -1.1812 0.0149 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7727 -0.1457 0.1052 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0769 -1.2567 0.0396 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4683 -2.6140 0.2899 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3344 -3.3038 -0.1988 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4479 0.5962 1.0395 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4670 1.5907 0.8051 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8733 1.1811 1.0267 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7465 1.9903 1.7206 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0552 1.6344 1.9381 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5710 0.4577 1.4804 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7213 -0.4074 0.7644 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3800 0.0019 0.5650 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2061 -1.5287 0.3260 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6037 -2.6683 -0.1486 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8959 0.1051 1.7047 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3512 2.6713 -2.3410 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8894 1.1116 -1.6745 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2708 2.7007 -0.8121 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2255 3.0825 -0.6182 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2691 0.1255 -1.4185 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9383 2.6561 -1.9440 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5631 1.0105 -2.2098 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0874 1.5663 -3.1786 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0769 1.7122 0.4886 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8890 -1.7745 -0.1390 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4910 -3.6876 -0.3073 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1890 0.8443 0.2216 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5644 -2.7014 1.3947 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4019 -2.8770 -0.2351 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2411 2.4356 1.4967 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3923 2.9266 2.1022 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7334 2.3006 2.4965 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7330 -0.6726 0.0118 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9278 -3.4535 0.6124 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8456 -3.2159 -0.8190 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5061 -2.6522 -0.8599 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6192 0.7931 1.8390 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 3 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 5 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 21 23 1 0 23 24 1 0 20 25 1 0 16 2 1 0 22 17 1 0 11 6 1 0 14 9 1 0 1 26 1 0 1 27 1 0 1 28 1 0 2 29 1 1 3 30 1 6 4 31 1 0 4 32 1 0 4 33 1 0 5 34 1 1 7 35 1 0 8 36 1 0 11 37 1 0 13 38 1 0 13 39 1 0 16 40 1 1 18 41 1 0 19 42 1 0 22 43 1 0 24 44 1 0 24 45 1 0 24 46 1 0 25 47 1 0 M END

Standard InCHIKey	JPDORDSJPIKURD-UAFHBQARSA-N
Standard InCHI	InChI=1S/C20H22O5/c1-11-12(2)20(14-5-7-16-18(9-14)24-10-23-16)25-19(11)13-4-6-15(21)17(8-13)22-3/h4-9,11-12,19-21H,10H2,1-3H3/t11-,12-,19+,20-/m0/s1
SMILES	C[C@H]1[C@H](C)[C@@H](c2ccc3c(c2)OCO3)O[C@H]1c1ccc(c(c1)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	342.15	Volume:	348.383 ? Van der Waals volume.
Dense:	0.982	LogP:	2.528 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.697 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.21 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	21.0
TPSA:	57.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.905	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.468	Fsp³:	0.4
MCE-18:	73.857 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.411	Fluc inhibitor:	0.8 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.034 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.068 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.243	Promiscuous compounds:	0.195

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.045	MDCK Permeability:	-4.817
Pgp-inhibitor:	0.331	Pgp-substrate:	0.024
PAMPA:	0.118 ? 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%):	0.07	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.683

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.713	MRP1:	0.903
Plasma Protein Binding (PPB):	96.889%	Volume Distribution (VD):	-0.085
Fu:	3.172% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.966
OATP1B3 inhibitor:	0.956	BCRP inhibitor:	0.09
BSEP inhibitor:	0.973

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.84
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.981
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.033	CYP2D6-substrate:	0.986
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.576
HLM stability:	0.022 ? 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):

7.413

Half-life (T1/2):

1.101

ADMET: Toxicity

hERG Blockers:	0.196	hERG Blockers (10um):	0.464
Human Hepatotoxicity (H-HT):	0.786	Drug-induced Liver Injury (DILI):	0.885
AMES Toxicity:	0.725	Rat Oral Acute Toxicity:	0.437
Maximum Recommended Daily Dose:	0.365	Skin Sensitization:	0.685
Carcinogencity:	0.762	Eye Corrosion:	0.096
Eye Irritation:	0.901	Respiratory Toxicity:	0.821
Drug-induced Neurotoxicity:	0.527	Ototoxicity:	0.312
Hematotoxicity:	0.52	Drug-induced Nephrotoxicity:	0.48
Genotoxicity:	0.825	RPMI-8226 Immunitoxicity:	0.187
A549 Cytotoxicity:	0.585	Hek293 Cytotoxicity:	0.575
BCF:	1.478 ? 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:	3.82 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.276 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.582 ? 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
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27214307]
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	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

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Non-molecular	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	5109.0	nM	PMID[27214307]

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 NPC228469 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	18268
0.1-0.2	25728
0.2-0.3	4845
0.3-0.4	800
0.4-0.5	124
0.5-0.6	44
0.6-0.7	12
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC142547
0.8125	Intermediate Similarity	NPC11258
0.8125	Intermediate Similarity	NPC21867
0.8125	Intermediate Similarity	NPC45774
0.8125	Intermediate Similarity	NPC74914
0.8036	Intermediate Similarity	NPC487682
0.7843	Intermediate Similarity	NPC135777
0.7407	Intermediate Similarity	NPC88640
0.7407	Intermediate Similarity	NPC101153
0.7407	Intermediate Similarity	NPC193666
0.7407	Intermediate Similarity	NPC123526
0.7407	Intermediate Similarity	NPC608725
0.7391	Intermediate Similarity	NPC282703
0.7391	Intermediate Similarity	NPC184733
0.7391	Intermediate Similarity	NPC128208
0.7391	Intermediate Similarity	NPC129570
0.7391	Intermediate Similarity	NPC63238
0.7391	Intermediate Similarity	NPC602603
0.7358	Intermediate Similarity	NPC488984
0.7358	Intermediate Similarity	NPC488985
0.7292	Intermediate Similarity	NPC57119
0.7292	Intermediate Similarity	NPC158471
0.7292	Intermediate Similarity	NPC226862
0.7174	Intermediate Similarity	NPC271208
0.7174	Intermediate Similarity	NPC233224
0.7174	Intermediate Similarity	NPC610263
0.7059	Intermediate Similarity	NPC487683
0.6984	Remote Similarity	NPC304048
0.6897	Remote Similarity	NPC471505
0.6897	Remote Similarity	NPC43514
0.6792	Remote Similarity	NPC488986
0.6393	Remote Similarity	NPC77861
0.6346	Remote Similarity	NPC158331
0.625	Remote Similarity	NPC7744
0.6226	Remote Similarity	NPC487685
0.6226	Remote Similarity	NPC136750
0.6226	Remote Similarity	NPC487684
0.6226	Remote Similarity	NPC266848
0.6061	Remote Similarity	NPC226153
0.5902	Remote Similarity	NPC179521
0.5893	Remote Similarity	NPC27843
0.5893	Remote Similarity	NPC7171
0.5862	Remote Similarity	NPC298317
0.5862	Remote Similarity	NPC255566
0.5833	Remote Similarity	NPC216929
0.5833	Remote Similarity	NPC312713
0.5833	Remote Similarity	NPC126935
0.5833	Remote Similarity	NPC65933
0.5833	Remote Similarity	NPC57268
0.5833	Remote Similarity	NPC172676
0.5806	Remote Similarity	NPC302506
0.5806	Remote Similarity	NPC241846
0.5806	Remote Similarity	NPC93610
0.5769	Remote Similarity	NPC242807
0.5769	Remote Similarity	NPC142985
0.5769	Remote Similarity	NPC153739
0.5625	Remote Similarity	NPC265154
0.5614	Remote Similarity	NPC274356
0.5614	Remote Similarity	NPC101748
0.5517	Remote Similarity	NPC177868
0.549	Remote Similarity	NPC31530
0.5472	Remote Similarity	NPC480478
0.5455	Remote Similarity	NPC147379
0.5455	Remote Similarity	NPC469480
0.5385	Remote Similarity	NPC50683
0.5385	Remote Similarity	NPC72046
0.5385	Remote Similarity	NPC261812
0.5385	Remote Similarity	NPC112571
0.5385	Remote Similarity	NPC65183
0.5385	Remote Similarity	NPC285725
0.5283	Remote Similarity	NPC204215
0.5185	Remote Similarity	NPC115207
0.5185	Remote Similarity	NPC158079
0.5185	Remote Similarity	NPC228346
0.5185	Remote Similarity	NPC40432
0.5185	Remote Similarity	NPC161557
0.5179	Remote Similarity	NPC227160
0.5179	Remote Similarity	NPC82111
0.5179	Remote Similarity	NPC483654
0.5079	Remote Similarity	NPC487677
0.5079	Remote Similarity	NPC487675
0.5079	Remote Similarity	NPC46880
0.5079	Remote Similarity	NPC477702

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC228469 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3808
0.1-0.2	5061
0.2-0.3	266
0.3-0.4	14
0.4-0.5	1
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