NPASS Compound

Natural Product: NPC478416

Natural Product ID	NPC478416
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OGYFHXKTNHMCSJ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	134139861
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins [CHEMONTID:0001710] Hydrolyzable tannins

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 70 75 0 0 0 0 0 0 0 0999 V2000 -5.3304 -2.0522 -0.6467 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5565 -1.1041 -1.4463 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2657 -0.9108 -0.9788 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9117 0.1340 -0.1772 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9003 1.1354 0.2536 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1598 1.1685 -0.3161 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9972 2.2211 0.0096 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6309 3.2259 0.8652 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3709 3.1682 1.4160 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5065 2.1215 1.1101 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2050 2.0995 1.7842 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1218 1.3585 1.1252 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5853 0.2491 0.2875 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6681 -0.7155 -0.0953 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7273 -0.6334 0.3583 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6962 -0.0019 -0.3791 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3079 0.5664 -1.6573 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3102 1.3518 -2.3809 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6749 1.2686 -1.8437 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6582 1.8273 -2.6321 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9820 1.8355 -2.2577 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3129 1.2641 -1.0599 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3545 0.6859 -0.2293 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0434 0.7000 -0.6385 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9976 0.0381 0.1387 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2626 -0.5393 1.3477 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2512 -1.1820 2.0794 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9890 -1.2199 1.5702 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0362 -1.8655 2.3010 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6021 -1.7444 3.2869 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0371 -3.1127 3.2449 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5044 -0.5243 1.9451 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6646 0.5381 2.9506 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9483 2.4070 -3.0732 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0453 -1.7507 -0.9050 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3194 -1.8928 -1.3703 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7533 -2.8981 -2.1781 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2444 -4.1528 -1.8358 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1022 -2.6994 -1.2736 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4765 4.2834 1.1892 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6893 -2.5511 0.1024 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7657 -2.8302 -1.2901 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1253 -1.5522 -0.0817 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5221 0.4963 -1.0176 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0101 2.2890 -0.4175 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0705 3.9705 2.1014 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3734 1.6817 2.8257 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8541 3.1737 1.8998 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6001 2.0762 0.4208 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4035 1.0217 1.9085 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3766 1.1624 -1.5436 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0093 -0.2975 -2.3313 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3663 1.0959 -3.4792 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0322 2.4468 -2.3770 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4374 2.2930 -3.5959 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3331 1.2550 -0.7410 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7091 0.2313 0.6502 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 -2.8050 2.1320 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2744 -3.6747 2.6697 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0050 -3.1862 2.7095 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1347 -3.5460 4.2388 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4064 1.4718 2.4122 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9975 0.3159 3.8001 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7351 0.4943 3.2289 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8806 2.0264 -3.0048 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6033 -4.9647 -2.3030 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2291 -4.2969 -2.3703 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3873 -4.3432 -0.7619 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1049 -3.0004 -2.2404 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7869 4.8976 0.4249 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 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 27 30 1 0 30 31 1 0 26 32 1 0 32 33 1 0 21 34 1 0 14 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 35 39 1 0 8 40 1 0 36 3 1 0 13 4 1 0 28 15 1 0 10 5 1 0 25 16 1 0 24 19 1 0 1 41 1 0 1 42 1 0 1 43 1 0 6 44 1 0 7 45 1 0 9 46 1 0 11 47 1 0 11 48 1 0 12 49 1 0 12 50 1 0 17 51 1 0 17 52 1 0 18 53 1 0 18 54 1 0 20 55 1 0 22 56 1 0 23 57 1 0 29 58 1 0 31 59 1 0 31 60 1 0 31 61 1 0 33 62 1 0 33 63 1 0 33 64 1 0 34 65 1 0 38 66 1 0 38 67 1 0 38 68 1 0 39 69 1 0 40 70 1 0 M END

Standard InCHIKey	OGYFHXKTNHMCSJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C32H30O8/c1-37-29-23-19-11-7-17(33)13-15(19)5-9-21(23)25(27(35)31(29)39-3)26-22-10-6-16-14-18(34)8-12-20(16)24(22)30(38-2)32(40-4)28(26)36/h7-8,11-14,33-36H,5-6,9-10H2,1-4H3
SMILES	COc1c2-c3ccc(cc3CCc2c(c2c3CCc4cc(ccc4-c3c(c(c2O)OC)OC)O)c(c1OC)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	542.19	Volume:	549.374 ? Van der Waals volume.
Dense:	0.987	LogP:	3.435 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.169 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.77 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	32.0
TPSA:	117.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.252	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.1	Fsp³:	0.25
MCE-18:	79.2 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.995	Fluc inhibitor:	0.662 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.518 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.949 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.265	Promiscuous compounds:	0.156

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.061	MDCK Permeability:	-4.781
Pgp-inhibitor:	0.016	Pgp-substrate:	0.338
PAMPA:	0.666 ? 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):	0.002
20% Bioavailability (F20%):	0.384	30% Bioavailability (F30%):	0.223
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.336	MRP1:	0.982
Plasma Protein Binding (PPB):	96.766%	Volume Distribution (VD):	0.056
Fu:	2.996% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.909
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.6
BSEP inhibitor:	0.792

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.393
CYP2C19-inhibitor:	0.979	CYP2C19-substrate:	0.973
CYP2C9-inhibitor:	0.994	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.74	CYP2D6-substrate:	0.063
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.914	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

3.217

Half-life (T1/2):

1.77

ADMET: Toxicity

hERG Blockers:	0.521	hERG Blockers (10um):	0.789
Human Hepatotoxicity (H-HT):	0.694	Drug-induced Liver Injury (DILI):	0.05
AMES Toxicity:	0.59	Rat Oral Acute Toxicity:	0.788
Maximum Recommended Daily Dose:	0.968	Skin Sensitization:	0.949
Carcinogencity:	0.883	Eye Corrosion:	0.0
Eye Irritation:	0.01	Respiratory Toxicity:	0.978
Drug-induced Neurotoxicity:	0.505	Ototoxicity:	0.888
Hematotoxicity:	0.38	Drug-induced Nephrotoxicity:	0.196
Genotoxicity:	0.934	RPMI-8226 Immunitoxicity:	0.104
A549 Cytotoxicity:	0.884	Hek293 Cytotoxicity:	0.952
BCF:	1.807 ? 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:	5.201 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.138 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.61 ? 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
NPO7428	Bletilla formosana	Species	Orchidaceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[27525452]
NPO7428	Bletilla formosana	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7428	Bletilla formosana	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7428	Bletilla formosana	Species	Orchidaceae	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	2

Activity Type	# Activity
Non-molecular	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2500.0	nM	PMID[27525452]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[27525452]

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 NPC478416 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	28402
0.1-0.2	18664
0.2-0.3	2646
0.3-0.4	103
0.4-0.5	28
0.5-0.6	8
0.6-0.7	6
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	Natural Product ID
0.6957	Remote Similarity	NPC108198
0.6809	Remote Similarity	NPC69029
0.6735	Remote Similarity	NPC262297
0.6735	Remote Similarity	NPC258780
0.64	Remote Similarity	NPC294436
0.617	Remote Similarity	NPC228503
0.5893	Remote Similarity	NPC478417
0.5789	Remote Similarity	NPC191462
0.569	Remote Similarity	NPC31342
0.5686	Remote Similarity	NPC200557
0.549	Remote Similarity	NPC138248
0.5333	Remote Similarity	NPC58963
0.5238	Remote Similarity	NPC478412
0.5156	Remote Similarity	NPC206158

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC478416 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5924
0.1-0.2	3166
0.2-0.3	59
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