NPASS Compound

Natural Product: NPC513066

Natural Product ID	NPC513066
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S},3~{S})-6-[(2~{S},3~{R},4~{R})-3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-yl]-2-(3,4-dihydroxyphenyl)chromane-3,5,7-triol
IUPAC Name	(2~{S},3~{S})-6-[(2~{S},3~{R},4~{R})-3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-yl]-2-(3,4-dihydroxyphenyl)chromane-3,5,7-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 66 71 0 0 0 0 0 0 0 0999 V2000 -7.6386 -3.6124 -2.7608 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8098 -2.7978 -1.9746 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3635 -3.1911 -0.7465 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5407 -2.3505 0.0031 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1588 -1.1132 -0.4690 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2922 -0.2166 0.3082 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7270 1.1066 0.3326 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8323 2.1194 0.6229 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3335 3.4106 0.6455 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5074 4.4802 0.9262 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9732 5.7863 0.9579 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1586 4.2483 1.1878 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6888 2.9519 1.1580 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4923 1.8712 0.8812 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0391 0.4719 0.8366 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6054 0.2632 0.8044 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1024 0.4300 1.9878 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5275 0.7762 3.1807 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4740 0.2621 2.0538 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1935 -0.0810 0.9329 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5674 -0.2597 0.9507 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2396 -0.0740 -0.2964 C 0 0 1 0 0 0 0 0 0 0 0 0 5.6771 -0.2387 -0.0611 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2279 0.3873 1.0472 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5688 0.2998 1.3630 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4228 -0.4318 0.5650 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7788 -0.5464 0.8457 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8872 -1.0584 -0.5391 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7445 -1.7940 -1.3419 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5327 -0.9641 -0.8493 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6334 -1.0456 -1.2530 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5700 -2.2934 -0.6148 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2018 -0.6174 -1.4916 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5123 -0.2493 -0.2397 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1343 -0.0801 -0.3043 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5292 -0.2563 -1.5034 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8495 -0.2232 -0.2196 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5012 -1.5630 -0.3632 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6200 -0.7354 -1.7103 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4448 -1.5707 -2.4687 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4014 -4.1197 -2.3556 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6702 -4.1686 -0.3827 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2074 -2.6980 0.9723 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2056 -0.5523 1.3722 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3796 3.6115 0.4449 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8840 6.3264 1.8156 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4725 5.0538 1.4126 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6248 2.8050 1.3640 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4047 0.0174 1.8128 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0755 0.0989 3.6962 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0387 0.3896 2.9718 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0819 0.9631 -0.6760 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5820 0.9717 1.6966 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0080 0.7837 2.2247 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3727 0.2618 0.8761 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0448 -1.3687 -2.2156 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1251 -1.4612 -1.7188 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1740 -1.1353 -2.2002 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3983 -2.8245 -0.7468 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1361 0.1820 -2.2623 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6711 -1.5135 -1.9108 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0064 -0.4386 -2.3513 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8551 0.3527 -1.1426 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1081 -1.9849 -1.0003 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3633 0.2255 -2.1518 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8091 -1.2783 -3.4440 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 10 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 26 28 1 0 28 29 1 0 28 30 2 0 22 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 34 35 2 0 35 36 1 0 15 37 1 0 37 38 1 0 5 39 1 0 39 40 2 0 40 2 1 0 37 6 1 0 14 8 1 0 35 16 1 0 34 20 1 0 30 23 1 0 1 41 1 0 3 42 1 0 4 43 1 0 6 44 1 1 9 45 1 0 11 46 1 0 12 47 1 0 13 48 1 0 15 49 1 1 18 50 1 0 19 51 1 0 22 52 1 6 24 53 1 0 25 54 1 0 27 55 1 0 29 56 1 0 30 57 1 0 31 58 1 6 32 59 1 0 33 60 1 0 33 61 1 0 36 62 1 0 37 63 1 6 38 64 1 0 39 65 1 0 40 66 1 0 M END

Standard InCHIKey	KTNXYFUXAOFFIX-YURATHNJSA-N
Standard InCHI	InChI=1S/C30H26O10/c31-15-4-1-13(2-5-15)30-28(38)25(17-7-6-16(32)10-23(17)40-30)26-21(35)12-24-18(27(26)37)11-22(36)29(39-24)14-3-8-19(33)20(34)9-14/h1-10,12,22,25,28-38H,11H2/t22-,25+,28+,29-,30-/m0/s1
SMILES	OC1=CC=C([C@@H]2OC3=CC(O)=CC=C3[C@H](C3=C(O)C=C4O[C@@H](C5=CC=C(O)C(O)=C5)[C@@H](O)CC4=C3O)[C@H]2O)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	546.15	Volume:	532.362 ? Van der Waals volume.
Dense:	1.026	LogP:	1.464 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.742 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.161 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	34.0
TPSA:	180.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	8.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.177	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.359	Fsp³:	0.2
MCE-18:	120.0 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.902	Fluc inhibitor:	0.377 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.104 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.387 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.541	Promiscuous compounds:	0.158

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.771	MDCK Permeability:	-4.945
Pgp-inhibitor:	0.0	Pgp-substrate:	0.276
PAMPA:	0.515 ? 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%):	0.959	30% Bioavailability (F30%):	0.993
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.92
Plasma Protein Binding (PPB):	93.211%	Volume Distribution (VD):	0.04
Fu:	10.272% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.024
BSEP inhibitor:	0.181

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.988	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.0 ? 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):

10.905

Half-life (T1/2):

3.516

ADMET: Toxicity

hERG Blockers:	0.306	hERG Blockers (10um):	0.771
Human Hepatotoxicity (H-HT):	0.943	Drug-induced Liver Injury (DILI):	0.652
AMES Toxicity:	0.071	Rat Oral Acute Toxicity:	0.277
Maximum Recommended Daily Dose:	0.989	Skin Sensitization:	0.999
Carcinogencity:	0.002	Eye Corrosion:	0.0
Eye Irritation:	0.678	Respiratory Toxicity:	0.873
Drug-induced Neurotoxicity:	0.264	Ototoxicity:	0.966
Hematotoxicity:	0.051	Drug-induced Nephrotoxicity:	0.222
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.036
A549 Cytotoxicity:	0.988	Hek293 Cytotoxicity:	0.983
BCF:	1.191 ? 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:	3.821 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.647 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.206 ? 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
NPO52760	Acacia luederitzii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO59162	Julbernardia globiflora	Species	Fabaceae	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

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 NPC513066 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	25061
0.1-0.2	21730
0.2-0.3	2720
0.3-0.4	232
0.4-0.5	66
0.5-0.6	28
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9649	High Similarity	NPC82917
0.7385	Intermediate Similarity	NPC294558
0.7385	Intermediate Similarity	NPC18185
0.7385	Intermediate Similarity	NPC263940
0.7206	Intermediate Similarity	NPC70409
0.7206	Intermediate Similarity	NPC204770
0.7206	Intermediate Similarity	NPC600551
0.7206	Intermediate Similarity	NPC601980
0.7206	Intermediate Similarity	NPC602065
0.7206	Intermediate Similarity	NPC611024
0.6912	Remote Similarity	NPC313116
0.6912	Remote Similarity	NPC603340
0.6857	Remote Similarity	NPC226809
0.6528	Remote Similarity	NPC600630
0.6528	Remote Similarity	NPC607896
0.6528	Remote Similarity	NPC611369
0.6471	Remote Similarity	NPC601999
0.6389	Remote Similarity	NPC601997
0.6389	Remote Similarity	NPC609211
0.6389	Remote Similarity	NPC610665
0.5968	Remote Similarity	NPC261619
0.5968	Remote Similarity	NPC61477
0.5968	Remote Similarity	NPC78770
0.5968	Remote Similarity	NPC219876
0.5968	Remote Similarity	NPC126029
0.5968	Remote Similarity	NPC15658
0.5854	Remote Similarity	NPC478340
0.5775	Remote Similarity	NPC58190
0.5775	Remote Similarity	NPC108811
0.5775	Remote Similarity	NPC170103
0.5775	Remote Similarity	NPC236202
0.5775	Remote Similarity	NPC262911
0.5775	Remote Similarity	NPC202742
0.5738	Remote Similarity	NPC601844
0.5694	Remote Similarity	NPC246202
0.5694	Remote Similarity	NPC224161
0.5694	Remote Similarity	NPC46335
0.5694	Remote Similarity	NPC279406
0.5694	Remote Similarity	NPC486519
0.5645	Remote Similarity	NPC207179
0.5645	Remote Similarity	NPC167571
0.5645	Remote Similarity	NPC278552
0.5294	Remote Similarity	NPC178054
0.5294	Remote Similarity	NPC78074
0.519	Remote Similarity	NPC278548
0.5057	Remote Similarity	NPC478337
0.5057	Remote Similarity	NPC478338
0.5056	Remote Similarity	NPC159526

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC513066 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4982
0.1-0.2	4070
0.2-0.3	87
0.3-0.4	9
0.4-0.5	0
0.5-0.6	2
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
0.5968	Remote Similarity	NPD1612	Clinical (unspecified phase)
0.5968	Remote Similarity	NPD1613	Phase 4

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