NPASS Compound

Natural Product: NPC247255

Natural Product ID	NPC247255
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YYTOQVPOKBYUID-SZBJCMRMSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11968846
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0002817] Dibenzopyrans [CHEMONTID:0000200] Xanthenes [CHEMONTID:0000204] Xanthones

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 71 75 0 0 0 0 0 0 0 0999 V2000 -5.8070 -0.1103 -0.0180 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1272 0.2563 1.3007 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1781 -0.9496 2.1666 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3080 -0.8586 3.3995 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4802 0.3923 3.2727 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8645 0.3839 1.8673 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9170 0.8060 1.0310 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9012 1.2956 1.8354 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6780 1.1098 1.4071 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3557 1.3235 2.4673 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4922 2.7976 2.6882 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2180 3.5588 1.6329 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0730 5.0511 1.7890 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3725 5.3748 1.4798 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0143 3.1454 0.3348 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1795 1.7821 0.1448 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0386 1.2524 -0.2199 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4614 0.3330 -1.1021 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8422 0.1562 -1.2169 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3961 -0.7587 -2.0817 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5765 -1.5201 -2.8579 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2346 -1.3638 -2.7643 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6229 -0.4317 -1.8818 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6901 -0.3998 -1.9006 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9190 -0.5210 -2.0696 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0933 -2.4617 -3.7489 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3157 -3.1513 -4.4543 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4474 -2.5985 -3.8222 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0317 -3.5201 -4.6898 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3965 -3.6538 -4.7587 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1901 -2.8575 -3.9505 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6006 -1.9534 -3.1005 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2440 -1.7932 -3.0056 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6798 -0.9328 -2.1939 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5636 -2.9780 -4.0022 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2156 -4.3112 -5.4945 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0949 3.1672 3.9754 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5907 0.7782 2.0165 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5429 0.4701 4.2650 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4441 -1.9673 3.3889 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4992 -1.0862 2.6282 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7247 0.7758 -0.6767 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2847 -0.9385 -0.5204 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8799 -0.3119 0.1222 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7697 1.0501 1.7707 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9764 -1.8717 1.5920 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8593 -0.8693 4.3499 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1843 1.2675 3.3224 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6335 -0.6291 1.5049 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5967 -0.0014 1.1347 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0929 0.8062 3.4215 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6010 3.0535 2.6278 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3025 3.4925 1.8307 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1104 5.2981 2.8506 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6718 5.6418 1.1948 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9230 5.1297 2.2627 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8802 1.6595 -0.6925 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5002 0.7590 -0.6044 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5781 -1.9574 -3.3675 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5443 0.4225 -1.8428 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2273 -0.7870 -3.1522 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5098 -1.2974 -1.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8602 -4.3596 -5.4211 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2694 -1.3560 -2.4970 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0811 -2.8980 -4.8651 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6658 -5.0439 -5.0279 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8710 3.0790 4.5600 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1246 0.6262 2.8211 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7357 -0.0216 5.0872 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2766 -2.2992 2.4853 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5606 -1.6749 3.4214 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 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 12 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 21 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 31 35 1 0 29 36 1 0 11 37 1 0 10 38 1 0 5 39 1 0 4 40 1 0 3 41 1 0 7 2 1 0 16 9 1 0 23 18 1 0 33 28 1 0 34 20 1 0 1 42 1 0 1 43 1 0 1 44 1 0 2 45 1 1 3 46 1 6 4 47 1 1 5 48 1 6 6 49 1 6 9 50 1 6 10 51 1 1 11 52 1 1 12 53 1 1 13 54 1 0 13 55 1 0 14 56 1 0 16 57 1 6 19 58 1 0 22 59 1 0 25 60 1 0 25 61 1 0 25 62 1 0 30 63 1 0 32 64 1 0 35 65 1 0 36 66 1 0 37 67 1 0 38 68 1 0 39 69 1 0 40 70 1 0 41 71 1 0 M END

Standard InCHIKey	YYTOQVPOKBYUID-SZBJCMRMSA-N
Standard InCHI	InChI=1S/C26H30O15/c1-8-18(30)21(33)23(35)25(37-8)41-24-22(34)20(32)16(7-27)40-26(24)39-14-6-12-10(5-13(14)36-2)19(31)17-11(29)3-9(28)4-15(17)38-12/h3-6,8,16,18,20-30,32-35H,7H2,1-2H3/t8-,16+,18-,20+,21+,22-,23+,24+,25-,26+/m0/s1
SMILES	C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)O[C@@H]1[C@H]([C@@H]([C@@H](CO)O[C@H]1Oc1cc2c(cc1OC)c(=O)c1c(cc(cc1o2)O)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	582.16	Volume:	528.868 ? Van der Waals volume.
Dense:	1.101	LogP:	0.13 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.891 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.936 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	29.0
TPSA:	238.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	8.0	Rings:	5.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.153	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.649	Fsp³:	0.5
MCE-18:	119.436 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.619	Fluc inhibitor:	0.232 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.808 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.392 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.127	Promiscuous compounds:	0.436

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.421	MDCK Permeability:	-5.244
Pgp-inhibitor:	0.0	Pgp-substrate:	0.977
PAMPA:	0.996 ? 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):	0.917
20% Bioavailability (F20%):	0.246	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.188
Plasma Protein Binding (PPB):	80.675%	Volume Distribution (VD):	-0.197
Fu:	16.321% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.662
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.012
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.979
HLM stability:	0.223 ? 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):

1.417

Half-life (T1/2):

3.841

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.109
Human Hepatotoxicity (H-HT):	0.523	Drug-induced Liver Injury (DILI):	0.959
AMES Toxicity:	0.887	Rat Oral Acute Toxicity:	0.015
Maximum Recommended Daily Dose:	0.026	Skin Sensitization:	0.993
Carcinogencity:	0.151	Eye Corrosion:	0.0
Eye Irritation:	0.553	Respiratory Toxicity:	0.006
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.925
Hematotoxicity:	0.1	Drug-induced Nephrotoxicity:	0.237
Genotoxicity:	0.846	RPMI-8226 Immunitoxicity:	0.129
A549 Cytotoxicity:	0.295	Hek293 Cytotoxicity:	0.445
BCF:	0.352 ? 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:	3.019 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.659 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.733 ? 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
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	roots	n.a.	n.a.	PMID[16989524]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[22863942]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[24042007]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38838926]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	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 NPC247255 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	22471
0.1-0.2	23011
0.2-0.3	3615
0.3-0.4	561
0.4-0.5	176
0.5-0.6	20
0.6-0.7	3
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
0.6154	Remote Similarity	NPC239549
0.6022	Remote Similarity	NPC163242
0.6022	Remote Similarity	NPC272068
0.5957	Remote Similarity	NPC155877
0.5918	Remote Similarity	NPC220173
0.56	Remote Similarity	NPC179183
0.5484	Remote Similarity	NPC136761
0.5426	Remote Similarity	NPC170052
0.5426	Remote Similarity	NPC135846
0.5368	Remote Similarity	NPC254855
0.5368	Remote Similarity	NPC94610
0.5354	Remote Similarity	NPC240306
0.5306	Remote Similarity	NPC65003
0.5263	Remote Similarity	NPC476215
0.5253	Remote Similarity	NPC470444
0.5208	Remote Similarity	NPC95866
0.5192	Remote Similarity	NPC602448
0.5185	Remote Similarity	NPC607702
0.5146	Remote Similarity	NPC195257
0.514	Remote Similarity	NPC48984
0.51	Remote Similarity	NPC115674
0.5098	Remote Similarity	NPC32641
0.5098	Remote Similarity	NPC256188

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC247255 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5702
0.1-0.2	3364
0.2-0.3	76
0.3-0.4	7
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