NPASS Compound

Natural Product: NPC304745

Natural Product ID	NPC304745
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Keyakinin
IUPAC Name	3,5-dihydroxy-2-(4-hydroxyphenyl)-7-methoxy-6-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]chromen-4-one
Synonyms	Keyakinin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL520545
PubChem CID	44559819
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001737] Flavonoid C-glycosides

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 55 58 0 0 0 0 0 0 0 0999 V2000 -5.7027 2.1376 -2.5449 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4548 1.5089 -2.6779 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3203 0.4806 -1.5731 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1580 -0.1946 -1.5751 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7048 -0.8077 -0.4699 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3970 -0.5757 0.8254 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.7810 -0.0064 0.7425 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7335 1.1068 -0.2859 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9856 1.7027 -0.4419 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1585 0.4783 1.9955 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4144 -1.7324 1.6309 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2139 -0.6168 -0.3274 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6751 0.6132 -0.6273 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4969 1.6779 -1.0688 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9014 2.9349 -1.3699 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6776 0.7782 -0.4876 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4938 -0.2758 -0.0502 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9447 -1.5047 0.2484 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4216 -1.6636 0.1042 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9329 -2.9132 0.4150 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7764 -2.5001 0.6693 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3413 -3.6346 0.9544 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1535 -2.2560 0.7881 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6539 -1.0149 0.4791 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7668 -0.1061 0.0769 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0575 -0.6410 0.5615 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0936 -1.4319 0.9455 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4159 -0.9509 0.9802 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7219 0.3304 0.6305 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6708 1.1578 0.2341 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3881 0.6677 0.2076 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0296 0.8072 0.6644 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9809 -3.2728 1.2147 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7343 3.0117 -2.9692 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6903 2.2821 -2.6345 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4845 0.9656 -3.6559 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1321 -0.2764 -1.8131 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8059 -1.9227 -0.6634 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7764 0.1577 1.4212 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4835 -0.7781 0.3609 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9970 1.8463 0.0644 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4164 1.6800 0.4629 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9225 -0.0757 2.2931 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7815 -2.4468 1.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4339 3.3648 -0.4736 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0597 2.7277 -2.0890 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6135 3.5763 -1.8869 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1224 1.7255 -0.7162 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0069 -3.2737 1.3619 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9000 -2.4350 1.2234 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2036 -1.6278 1.2954 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9333 2.1640 -0.0378 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6123 1.3568 -0.1102 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1587 1.8085 0.8803 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6940 -4.1137 1.6722 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 7 8 1 0 8 9 1 0 7 10 1 0 6 11 1 0 5 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 13 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 18 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 24 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 29 32 1 0 23 33 1 0 8 3 1 0 19 12 1 0 31 26 1 0 25 17 1 0 1 34 1 0 2 35 1 0 2 36 1 0 3 37 1 6 5 38 1 6 6 39 1 1 7 40 1 6 8 41 1 1 9 42 1 0 10 43 1 0 11 44 1 0 15 45 1 0 15 46 1 0 15 47 1 0 16 48 1 0 20 49 1 0 27 50 1 0 28 51 1 0 30 52 1 0 31 53 1 0 32 54 1 0 33 55 1 0 M END

Standard InCHIKey	FWCFJKZMFJQKIT-WXZPSOLRSA-N
Standard InCHI	InChI=1S/C22H22O11/c1-31-10-6-11-13(17(27)19(29)21(32-11)8-2-4-9(24)5-3-8)16(26)14(10)22-20(30)18(28)15(25)12(7-23)33-22/h2-6,12,15,18,20,22-26,28-30H,7H2,1H3/t12-,15-,18+,20-,22+/m1/s1
SMILES	OC[C@H]1O[C@H]([C@@H]([C@H]([C@@H]1O)O)O)c1c(OC)cc2c(c1O)c(=O)c(c(o2)c1ccc(cc1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.12	Volume:	430.443 ? Van der Waals volume.
Dense:	1.074	LogP:	0.383 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.258 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.503 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	190.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.278	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.003	Fsp³:	0.318
MCE-18:	90.31 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.545	Fluc inhibitor:	0.157 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.762 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.81 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.092	Promiscuous compounds:	0.349

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.255	MDCK Permeability:	-5.284
Pgp-inhibitor:	0.0	Pgp-substrate:	0.139
PAMPA:	0.999 ? 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):	0.936
20% Bioavailability (F20%):	0.068	30% Bioavailability (F30%):	0.966
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.543
Plasma Protein Binding (PPB):	84.764%	Volume Distribution (VD):	-0.098
Fu:	12.401% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.649
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.108
BSEP inhibitor:	0.056

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.012
CYP2C9-inhibitor:	0.028	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.808
HLM stability:	0.176 ? 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):

3.961

Half-life (T1/2):

4.451

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.131
Human Hepatotoxicity (H-HT):	0.527	Drug-induced Liver Injury (DILI):	0.883
AMES Toxicity:	0.732	Rat Oral Acute Toxicity:	0.073
Maximum Recommended Daily Dose:	0.116	Skin Sensitization:	0.957
Carcinogencity:	0.399	Eye Corrosion:	0.0
Eye Irritation:	0.684	Respiratory Toxicity:	0.037
Drug-induced Neurotoxicity:	0.005	Ototoxicity:	0.77
Hematotoxicity:	0.161	Drug-induced Nephrotoxicity:	0.181
Genotoxicity:	0.793	RPMI-8226 Immunitoxicity:	0.072
A549 Cytotoxicity:	0.303	Hek293 Cytotoxicity:	0.457
BCF:	0.466 ? 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:	3.065 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.5 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.743 ? 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
NPO15288	Zelkova serrata	Species	Ulmaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10904	Panax arboreus	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15288	Zelkova serrata	Species	Ulmaceae	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
Inhibition	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1310	Individual protein	Xanthine dehydrogenase	Bos taurus	Inhibition	=	0.0	%	PMID[3379415]

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 NPC304745 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	21439
0.1-0.2	24529
0.2-0.3	3048
0.3-0.4	702
0.4-0.5	120
0.5-0.6	14
0.6-0.7	2
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
0.7838	Intermediate Similarity	NPC10807
0.7838	Intermediate Similarity	NPC161881
0.7162	Intermediate Similarity	NPC268193
0.6709	Remote Similarity	NPC602537
0.6282	Remote Similarity	NPC289771
0.5926	Remote Similarity	NPC220912
0.5778	Remote Similarity	NPC607513
0.561	Remote Similarity	NPC328740
0.561	Remote Similarity	NPC289774
0.5595	Remote Similarity	NPC323593
0.5595	Remote Similarity	NPC203500
0.5543	Remote Similarity	NPC606373
0.5529	Remote Similarity	NPC84265
0.5455	Remote Similarity	NPC111249
0.5342	Remote Similarity	NPC143799
0.5222	Remote Similarity	NPC601586
0.5176	Remote Similarity	NPC112701
0.5119	Remote Similarity	NPC209846
0.5114	Remote Similarity	NPC117260

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC304745 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4880
0.1-0.2	4186
0.2-0.3	74
0.3-0.4	9
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