NPASS Compound

Natural Product: NPC577073

Natural Product ID	NPC577073
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7-dihydroxy-2,8-bis(4-hydroxyphenyl)chromen-4-one
IUPAC Name	5,7-dihydroxy-2,8-bis(4-hydroxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones

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 41 44 0 0 0 0 0 0 0 0999 V2000 1.2365 -4.4208 0.0789 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9893 -3.1970 0.0644 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9422 -2.2152 -0.0925 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6100 -0.8790 -0.1005 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6205 0.1838 -0.2677 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9535 -0.0619 -0.4267 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8990 0.9325 -0.5832 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5028 2.2368 -0.5821 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3921 3.2910 -0.7337 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1625 2.5316 -0.4240 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2368 1.5185 -0.2693 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3431 -0.5718 0.0480 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6131 -1.4578 0.2018 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9442 -1.0369 0.3541 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2258 0.3896 0.3364 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5088 1.0089 -0.8743 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7857 2.3485 -0.9842 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7855 3.1240 0.1532 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0665 4.4873 0.0473 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5079 2.5329 1.3654 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2312 1.1827 1.4582 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9817 -1.9253 0.5182 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2821 -1.4771 0.6657 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6472 -3.2653 0.5260 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3501 -3.7021 0.3786 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0055 -5.0549 0.3856 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3192 -2.8005 0.2148 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9661 -2.5387 -0.2097 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3084 -1.0753 -0.4335 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9492 0.7003 -0.7070 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3145 3.2694 -0.3681 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8376 3.5771 -0.4221 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1702 1.7140 -0.1420 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5052 0.3835 -1.7636 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9935 2.7443 -1.9596 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8882 4.8336 -0.4265 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5203 3.1923 2.2384 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0175 0.7395 2.4083 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8840 -1.7040 1.4366 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4485 -3.9785 0.6538 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9227 -5.5600 -0.5059 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 2 0 4 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 2 0 18 19 1 0 18 20 1 0 20 21 2 0 14 22 1 0 22 23 1 0 22 24 2 0 24 25 1 0 25 26 1 0 25 27 2 0 27 2 1 0 11 5 1 0 27 13 1 0 21 15 1 0 3 28 1 0 6 29 1 0 7 30 1 0 9 31 1 0 10 32 1 0 11 33 1 0 16 34 1 0 17 35 1 0 19 36 1 0 20 37 1 0 21 38 1 0 23 39 1 0 24 40 1 0 26 41 1 0 M END

Standard InCHIKey	YXIOJBQQFQFXDQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H14O6/c22-13-5-1-11(2-6-13)18-10-17(26)20-16(25)9-15(24)19(21(20)27-18)12-3-7-14(23)8-4-12/h1-10,22-25H
SMILES	O=C1C=C(C2=CC=C(O)C=C2)OC2=C(C3=CC=C(O)C=C3)C(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	362.08	Volume:	361.287 ? Van der Waals volume.
Dense:	1.002	LogP:	3.611 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.807 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.81 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	24.0
TPSA:	111.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.43	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.455	Fsp³:	0.0
MCE-18:	23.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.954	Fluc inhibitor:	0.606 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.94 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.809 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.577	Promiscuous compounds:	0.902

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.156	MDCK Permeability:	-4.755
Pgp-inhibitor:	0.002	Pgp-substrate:	0.198
PAMPA:	0.919 ? 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%):	0.656	30% Bioavailability (F30%):	0.675
50% Bioavailability (F50%):	0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.933
Plasma Protein Binding (PPB):	96.549%	Volume Distribution (VD):	-0.465
Fu:	4.116% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.913
OATP1B3 inhibitor:	0.809	BCRP inhibitor:	0.131
BSEP inhibitor:	0.878

ADMET: Metabolism

CYP1A2-inhibitor:	0.014	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.157	CYP2C9-substrate:	0.631
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.019
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.675 ? 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):

4.222

Half-life (T1/2):

1.551

ADMET: Toxicity

hERG Blockers:	0.063	hERG Blockers (10um):	0.516
Human Hepatotoxicity (H-HT):	0.467	Drug-induced Liver Injury (DILI):	0.787
AMES Toxicity:	0.629	Rat Oral Acute Toxicity:	0.473
Maximum Recommended Daily Dose:	0.872	Skin Sensitization:	0.673
Carcinogencity:	0.752	Eye Corrosion:	0.018
Eye Irritation:	0.99	Respiratory Toxicity:	0.779
Drug-induced Neurotoxicity:	0.071	Ototoxicity:	0.095
Hematotoxicity:	0.048	Drug-induced Nephrotoxicity:	0.052
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.081
A549 Cytotoxicity:	0.477	Hek293 Cytotoxicity:	0.919
BCF:	1.176 ? 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:	4.111 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.503 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.224 ? 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
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	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 NPC577073 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	37279
0.1-0.2	10436
0.2-0.3	1552
0.3-0.4	448
0.4-0.5	104
0.5-0.6	25
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8889	High Similarity	NPC222713
0.7273	Intermediate Similarity	NPC67322
0.6897	Remote Similarity	NPC138299
0.678	Remote Similarity	NPC288840
0.6557	Remote Similarity	NPC254351
0.6471	Remote Similarity	NPC50898
0.6349	Remote Similarity	NPC606549
0.6061	Remote Similarity	NPC71061
0.6038	Remote Similarity	NPC296197
0.597	Remote Similarity	NPC194593
0.5846	Remote Similarity	NPC259757
0.5714	Remote Similarity	NPC265624
0.5692	Remote Similarity	NPC610480
0.5614	Remote Similarity	NPC301323
0.5588	Remote Similarity	NPC303485
0.5556	Remote Similarity	NPC55443
0.5484	Remote Similarity	NPC609354
0.5479	Remote Similarity	NPC607079
0.5455	Remote Similarity	NPC130230
0.541	Remote Similarity	NPC610914
0.5405	Remote Similarity	NPC604941
0.537	Remote Similarity	NPC216318
0.5362	Remote Similarity	NPC290830
0.5357	Remote Similarity	NPC279121
0.5312	Remote Similarity	NPC111112
0.5273	Remote Similarity	NPC78540
0.5217	Remote Similarity	NPC150908
0.5211	Remote Similarity	NPC121649
0.5161	Remote Similarity	NPC220062
0.5091	Remote Similarity	NPC172262
0.5088	Remote Similarity	NPC274121
0.5085	Remote Similarity	NPC241498
0.5075	Remote Similarity	NPC34089
0.5075	Remote Similarity	NPC196179

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC577073 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7475
0.1-0.2	1631
0.2-0.3	39
0.3-0.4	2
0.4-0.5	2
0.5-0.6	1
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
0.5357	Remote Similarity	NPD1511	Phase 2

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