NPASS Compound

Natural Product: NPC486097

Natural Product ID	NPC486097
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PGLILAKIYHOCKX-OGYNWANNSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	132566264
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans

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 72 77 0 0 0 0 0 0 0 0999 V2000 -3.1783 5.6834 1.3190 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2346 4.8233 1.8762 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6069 3.7984 1.1902 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4609 4.1057 0.5135 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1572 3.0802 -0.1625 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3062 1.7736 -0.1954 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5097 0.7888 -0.9458 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0320 -0.3667 -0.1398 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9912 -1.6659 -0.8440 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2776 -2.0079 -1.1692 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1061 -0.9202 -1.0353 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5145 -1.2780 -0.8132 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1117 -2.2707 -1.5506 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4474 -2.6273 -1.3596 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1929 -1.9608 -0.3984 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5810 -0.9712 0.3299 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2614 -0.6271 0.1332 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5288 -0.4754 1.2049 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7253 -1.2279 1.0632 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5010 -2.1117 -0.0155 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4944 -0.0628 0.0288 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5412 1.4072 -0.3171 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6715 1.4646 -1.3944 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4544 1.4787 0.4811 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0885 2.5074 1.1691 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2588 2.3001 1.8888 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5009 2.5253 1.2540 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9961 0.2396 0.5002 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0268 -0.2847 -0.2940 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5543 -1.4668 -1.0673 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7911 -2.3233 -1.3507 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2183 -2.8827 -0.0175 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1800 -1.8314 1.0590 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1231 -2.1295 2.0942 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3220 -3.4380 2.5242 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0590 -0.5583 0.5784 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4704 -3.4602 -0.1529 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5532 -3.2651 -2.3144 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1795 -1.0109 -2.3591 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0844 5.3862 0.4877 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9226 5.9256 2.1149 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6815 5.2045 0.4620 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6786 6.6359 1.0437 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0623 3.3813 -0.7262 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0327 0.4304 -1.8720 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6117 -0.3938 0.8899 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3917 -1.6239 -1.8055 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5398 -2.4321 -0.1710 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0676 -0.3332 -1.9906 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5576 -2.8072 -2.3055 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9323 -3.4060 -1.9313 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7994 0.1746 0.7350 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6030 -0.5919 0.8616 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8748 -1.8773 1.9653 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8596 -0.2765 1.0511 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5712 1.7252 -0.6068 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1691 1.9399 0.5600 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9870 3.4850 1.5646 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1810 1.6913 1.6088 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4521 2.4123 0.1522 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4271 0.4552 -1.0224 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7747 -2.0504 -0.5800 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5678 -1.6243 -1.7119 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5040 -3.6751 0.2580 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1516 -1.8929 1.5885 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3470 -1.4815 2.9820 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1078 -1.9017 1.7895 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5813 -3.9744 2.1095 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0112 -3.1600 0.6184 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9559 -4.1539 -2.1062 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9962 -1.7992 -2.9252 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0888 5.8561 -0.4295 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 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 11 21 1 0 21 22 1 0 22 23 1 0 6 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 24 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 33 36 1 0 32 37 1 0 31 38 1 0 30 39 1 0 4 40 1 0 25 3 1 0 36 29 1 0 23 7 1 0 21 8 1 0 17 12 1 0 20 15 1 0 1 41 1 0 1 42 1 0 1 43 1 0 5 44 1 0 7 45 1 6 8 46 1 1 9 47 1 0 9 48 1 0 11 49 1 6 13 50 1 0 14 51 1 0 17 52 1 0 19 53 1 0 19 54 1 0 21 55 1 1 22 56 1 0 22 57 1 0 27 58 1 0 27 59 1 0 27 60 1 0 29 61 1 6 30 62 1 1 31 63 1 6 32 64 1 1 33 65 1 1 34 66 1 0 34 67 1 0 35 68 1 0 37 69 1 0 38 70 1 0 39 71 1 0 40 72 1 0 M END

Standard InCHIKey	PGLILAKIYHOCKX-OGYNWANNSA-N
Standard InCHI	InChI=1S/C27H32O13/c1-33-25-15(29)6-12(24(26(25)34-2)40-27-21(32)20(31)19(30)18(7-28)39-27)23-14-9-35-22(13(14)8-36-23)11-3-4-16-17(5-11)38-10-37-16/h3-6,13-14,18-23,27-32H,7-10H2,1-2H3/t13-,14-,18+,19+,20-,21+,22+,23+,27-/m0/s1
SMILES	COc1c(cc([C@@H]2[C@H]3CO[C@H](c4ccc5c(c4)OCO5)[C@H]3CO2)c(c1OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	564.18	Volume:	522.664 ? Van der Waals volume.
Dense:	1.079	LogP:	0.081 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.72 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.47 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	31.0
TPSA:	174.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.313	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.796	Fsp³:	0.556
MCE-18:	125.0 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.648	Fluc inhibitor:	0.114 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.093 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.245 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.056	Promiscuous compounds:	0.181

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.948	MDCK Permeability:	-5.204
Pgp-inhibitor:	0.0	Pgp-substrate:	0.027
PAMPA:	0.802 ? 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%):	0.011	30% Bioavailability (F30%):	0.051
50% Bioavailability (F50%):	0.9

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.919	MRP1:	0.77
Plasma Protein Binding (PPB):	83.947%	Volume Distribution (VD):	-0.239
Fu:	17.624% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.005
BSEP inhibitor:	0.046

ADMET: Metabolism

CYP1A2-inhibitor:	0.347	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.683	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.017
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.532
CYP3A4-inhibitor:	0.161	CYP3A4-substrate:	0.984
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.002
HLM stability:	0.338 ? 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):

2.439

Half-life (T1/2):

3.945

ADMET: Toxicity

hERG Blockers:	0.027	hERG Blockers (10um):	0.106
Human Hepatotoxicity (H-HT):	0.89	Drug-induced Liver Injury (DILI):	0.992
AMES Toxicity:	0.945	Rat Oral Acute Toxicity:	0.027
Maximum Recommended Daily Dose:	0.058	Skin Sensitization:	0.999
Carcinogencity:	0.438	Eye Corrosion:	0.0
Eye Irritation:	0.13	Respiratory Toxicity:	0.015
Drug-induced Neurotoxicity:	0.057	Ototoxicity:	0.914
Hematotoxicity:	0.525	Drug-induced Nephrotoxicity:	0.855
Genotoxicity:	0.87	RPMI-8226 Immunitoxicity:	0.302
A549 Cytotoxicity:	0.491	Hek293 Cytotoxicity:	0.384
BCF:	0.768 ? 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:	3.27 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.193 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.084 ? 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
NPO40374	Terminalia citrina	Species	Combretaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27110635]
NPO40374	Terminalia citrina	Species	Combretaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	2

Activity Type	# Activity
Cell line	2

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
NPT83	Cell line	MCF7	Homo sapiens	Activity	<	0.01	uM	PMID[27110635]
NPT396	Cell line	T47D	Homo sapiens	Activity	<	0.01	uM	PMID[27110635]

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 NPC486097 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	19272
0.1-0.2	26184
0.2-0.3	3558
0.3-0.4	700
0.4-0.5	101
0.5-0.6	20
0.6-0.7	16
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8571	High Similarity	NPC486099
0.8077	Intermediate Similarity	NPC486098
0.7975	Intermediate Similarity	NPC486103
0.7342	Intermediate Similarity	NPC486105
0.7	Intermediate Similarity	NPC486106
0.6914	Remote Similarity	NPC486100
0.6914	Remote Similarity	NPC486101
0.6667	Remote Similarity	NPC279298
0.6579	Remote Similarity	NPC276753
0.6579	Remote Similarity	NPC205796
0.6494	Remote Similarity	NPC246947
0.6463	Remote Similarity	NPC38041
0.6463	Remote Similarity	NPC22150
0.6395	Remote Similarity	NPC186316
0.6375	Remote Similarity	NPC486104
0.6375	Remote Similarity	NPC486102
0.6341	Remote Similarity	NPC286235
0.6145	Remote Similarity	NPC51328
0.6145	Remote Similarity	NPC55158
0.6	Remote Similarity	NPC486109
0.6	Remote Similarity	NPC486108
0.5974	Remote Similarity	NPC95392
0.5974	Remote Similarity	NPC84013
0.5974	Remote Similarity	NPC55715
0.5974	Remote Similarity	NPC35877
0.5854	Remote Similarity	NPC216129
0.5854	Remote Similarity	NPC130449
0.5854	Remote Similarity	NPC248132
0.5679	Remote Similarity	NPC486107
0.5618	Remote Similarity	NPC469586
0.5543	Remote Similarity	NPC478055
0.5316	Remote Similarity	NPC88640
0.5316	Remote Similarity	NPC101153
0.5316	Remote Similarity	NPC193666
0.5316	Remote Similarity	NPC123526
0.5316	Remote Similarity	NPC608725
0.5213	Remote Similarity	NPC185307
0.5158	Remote Similarity	NPC112861
0.5111	Remote Similarity	NPC471063
0.5063	Remote Similarity	NPC298317
0.5063	Remote Similarity	NPC255566

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC486097 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5036
0.1-0.2	4004
0.2-0.3	100
0.3-0.4	10
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