NPASS Compound

Natural Product: NPC521353

Natural Product ID	NPC521353
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-chromen-4-one
IUPAC Name	8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-chromen-4-one
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 59 64 0 0 0 0 0 0 0 0999 V2000 -4.9081 -3.4373 2.1153 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2701 -2.6067 1.4238 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3376 -1.7280 1.9490 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6583 -0.8309 1.1540 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6711 0.1065 1.6765 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3541 0.1538 3.0072 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3882 1.0933 3.4166 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2317 1.9466 2.5324 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1689 2.8359 3.0323 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0998 1.8854 1.1950 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5329 2.7693 0.2337 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0144 3.9988 -0.0569 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1800 4.4612 0.5376 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5835 4.8610 -0.9804 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7382 4.4980 -1.6228 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3388 5.3571 -2.5467 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2924 3.2747 -1.3408 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6997 2.4283 -0.4300 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2245 1.2798 -0.1684 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3447 0.8800 -0.7648 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8643 -0.4215 -0.4134 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0127 -0.9231 -0.9732 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5131 -2.1745 -0.6359 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8474 -2.9367 0.2812 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3508 -4.1835 0.6137 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6789 -2.4380 0.8574 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0248 -3.2443 1.7907 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1879 -1.2088 0.5256 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9909 1.6651 -1.6804 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4446 2.9045 -1.9773 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0170 3.6372 -2.8093 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0404 0.9700 0.7991 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9548 -0.8672 -0.1268 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8035 -1.6431 -0.7138 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0410 -1.5977 -2.0809 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9477 -2.4324 -2.6815 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1771 -2.3725 -4.0750 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6318 -3.3323 -1.8970 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4241 -3.4072 -0.5406 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1145 -4.3157 0.2526 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4988 -2.5543 0.0677 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1541 -1.7657 3.0171 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8166 -0.4966 3.7296 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1625 1.1007 4.4840 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1965 3.8241 2.7783 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9927 4.5302 -0.0611 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1524 5.8249 -1.2068 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2909 5.0871 -3.5159 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5785 -0.3443 -1.7138 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4084 -2.5379 -1.0879 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2765 -4.3549 0.9585 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6010 -3.6546 2.5230 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2888 -0.8006 0.9552 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9097 1.3887 -2.1986 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3216 0.8973 -0.2402 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4698 -0.8646 -2.6519 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1592 -2.2856 -4.3266 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3452 -3.9953 -2.3409 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8536 -3.9037 0.8391 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 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 8 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 24 26 1 0 26 27 1 0 26 28 2 0 20 29 2 0 29 30 1 0 30 31 2 0 10 32 2 0 4 33 1 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 1 0 36 38 2 0 38 39 1 0 39 40 1 0 39 41 2 0 41 2 1 0 32 5 1 0 41 34 1 0 18 11 1 0 28 21 1 0 30 17 1 0 3 42 1 0 6 43 1 0 7 44 1 0 9 45 1 0 13 46 1 0 14 47 1 0 16 48 1 0 22 49 1 0 23 50 1 0 25 51 1 0 27 52 1 0 28 53 1 0 29 54 1 0 32 55 1 0 35 56 1 0 37 57 1 0 38 58 1 0 40 59 1 0 M END

Standard InCHIKey	TWWVGBFACRJZQC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C30H18O11/c31-14-7-19(35)28-22(38)10-24(40-26(28)8-14)12-1-3-16(32)15(5-12)27-20(36)9-21(37)29-23(39)11-25(41-30(27)29)13-2-4-17(33)18(34)6-13/h1-11,31-37H
SMILES	O=C1C=C(C2=CC=C(O)C(C3=C(O)C=C(O)C4=C3OC(C3=CC=C(O)C(O)=C3)=CC4=O)=C2)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	554.08	Volume:	530.606 ? Van der Waals volume.
Dense:	1.044	LogP:	4.123 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.487 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.203 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	202.03 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.148	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.139	Fsp³:	0.0
MCE-18:	37.0 ? 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:	0.996	Fluc inhibitor:	0.606 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.988 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.975 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.65	Promiscuous compounds:	0.915

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.617	MDCK Permeability:	-4.823
Pgp-inhibitor:	0.0	Pgp-substrate:	0.402
PAMPA:	0.476 ? 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):	0.001
20% Bioavailability (F20%):	0.942	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.952
Plasma Protein Binding (PPB):	97.122%	Volume Distribution (VD):	-0.525
Fu:	2.012% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.898
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.985
BSEP inhibitor:	0.514

ADMET: Metabolism

CYP1A2-inhibitor:	0.318	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.021	CYP2C9-substrate:	0.638
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.168
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.959 ? 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):

2.905

Half-life (T1/2):

2.222

ADMET: Toxicity

hERG Blockers:	0.031	hERG Blockers (10um):	0.541
Human Hepatotoxicity (H-HT):	0.387	Drug-induced Liver Injury (DILI):	0.985
AMES Toxicity:	0.812	Rat Oral Acute Toxicity:	0.666
Maximum Recommended Daily Dose:	0.987	Skin Sensitization:	0.908
Carcinogencity:	0.763	Eye Corrosion:	0.002
Eye Irritation:	0.997	Respiratory Toxicity:	0.886
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.092
Hematotoxicity:	0.01	Drug-induced Nephrotoxicity:	0.004
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.069
A549 Cytotoxicity:	0.938	Hek293 Cytotoxicity:	0.959
BCF:	1.113 ? 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:	4.359 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.799 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.541 ? 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
NPO13468	Cryptomeria japonica	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13468	Cryptomeria japonica	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13468	Cryptomeria japonica	Species	Cupressaceae	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 NPC521353 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	40351
0.1-0.2	7691
0.2-0.3	1161
0.3-0.4	506
0.4-0.5	99
0.5-0.6	23
0.6-0.7	14
0.7-0.8	1
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8689	High Similarity	NPC610480
0.8644	High Similarity	NPC138299
0.7612	Intermediate Similarity	NPC303485
0.75	Intermediate Similarity	NPC279121
0.7164	Intermediate Similarity	NPC259757
0.6765	Remote Similarity	NPC603692
0.6618	Remote Similarity	NPC254351
0.6528	Remote Similarity	NPC194593
0.6418	Remote Similarity	NPC111112
0.6389	Remote Similarity	NPC290830
0.6389	Remote Similarity	NPC71061
0.6324	Remote Similarity	NPC291746
0.6271	Remote Similarity	NPC50898
0.6216	Remote Similarity	NPC121649
0.6167	Remote Similarity	NPC222713
0.6167	Remote Similarity	NPC175013
0.6133	Remote Similarity	NPC601565
0.6087	Remote Similarity	NPC288840
0.6027	Remote Similarity	NPC150908
0.597	Remote Similarity	NPC67322
0.5811	Remote Similarity	NPC600972
0.5738	Remote Similarity	NPC78540
0.5625	Remote Similarity	NPC610974
0.5588	Remote Similarity	NPC183950
0.5556	Remote Similarity	NPC274121
0.5469	Remote Similarity	NPC213216
0.5441	Remote Similarity	NPC52005
0.5397	Remote Similarity	NPC275772
0.5397	Remote Similarity	NPC20791
0.5385	Remote Similarity	NPC215203
0.5333	Remote Similarity	NPC606549
0.5312	Remote Similarity	NPC179271
0.525	Remote Similarity	NPC265624
0.5238	Remote Similarity	NPC17286
0.5224	Remote Similarity	NPC231772
0.5224	Remote Similarity	NPC601901
0.5217	Remote Similarity	NPC12200
0.5205	Remote Similarity	NPC112954
0.5156	Remote Similarity	NPC70136
0.5128	Remote Similarity	NPC72425
0.5075	Remote Similarity	NPC605617
0.5063	Remote Similarity	NPC186227

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC521353 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8051
0.1-0.2	1064
0.2-0.3	30
0.3-0.4	3
0.4-0.5	0
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
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
0.75	Intermediate Similarity	NPD1511	Phase 2
0.5397	Remote Similarity	NPD1512	Phase 3

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