NPASS Compound

Natural Product: NPC529502

Natural Product ID	NPC529502
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-hydroxy-3-[4-hydroxy-3-[2-hydroxy-5-(7-hydroxy-4-oxo-chromen-3-yl)phenyl]phenyl]chromen-4-one
IUPAC Name	7-hydroxy-3-[4-hydroxy-3-[2-hydroxy-5-(7-hydroxy-4-oxo-chromen-3-yl)phenyl]phenyl]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:0002506] Isoflavonoids [CHEMONTID:0002901] Isoflav-2-enes [CHEMONTID:0000494] Isoflavones

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 56 61 0 0 0 0 0 0 0 0999 V2000 -2.9835 -0.6392 0.9382 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0464 -0.4364 0.3176 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9845 -0.1407 -1.0203 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7433 -0.0459 -1.7770 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6240 -0.6431 -3.0361 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4620 -0.5672 -3.7698 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3795 0.1136 -3.2591 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8167 0.2247 -3.9498 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4520 0.7243 -2.0090 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7093 1.4390 -1.4919 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6760 0.8245 -0.7313 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7693 1.4947 -0.2437 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8012 0.8529 0.5643 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2883 1.4572 1.7062 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2166 0.9044 2.4536 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7649 -0.2591 2.1937 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7453 -0.8091 3.0114 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3199 -2.0331 2.7351 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3023 -2.5762 3.5613 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8835 -2.6985 1.6082 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9091 -2.1483 0.7984 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3288 -0.9257 1.0662 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3507 -0.3774 0.2499 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9583 -0.9882 -0.7740 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8842 2.8423 -0.5413 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9456 3.5088 -1.2989 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8647 2.7885 -1.7651 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1165 3.4043 -2.5351 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6323 0.6253 -1.3067 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1714 0.0801 -1.6885 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3227 0.0148 -1.0873 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4469 -0.2644 0.1937 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6911 -0.3243 0.7953 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7853 -0.6190 2.1375 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0085 -0.6916 2.7905 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6399 -0.8529 2.8752 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3833 -0.7912 2.2619 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3032 -0.4976 0.9284 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5045 -1.1700 -3.3987 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3749 -1.0275 -4.7366 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8512 0.3844 -4.9577 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5885 -0.2263 -0.4980 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8477 2.4298 1.9465 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0768 -0.2627 3.9019 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2476 -2.2342 3.5971 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3407 -3.6565 1.4016 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5597 -2.6698 -0.0946 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7553 3.3950 -0.1580 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0470 4.5741 -1.5276 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2354 3.9101 -3.3604 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7127 1.0955 -0.3255 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1611 0.3156 -2.7431 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5803 -0.1373 0.1983 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3811 0.2043 3.1330 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7167 -1.0809 3.9143 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4771 -0.9674 2.8057 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 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 18 19 1 0 18 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 12 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 9 29 2 0 3 30 2 0 30 31 1 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 34 36 2 0 36 37 1 0 37 38 2 0 38 2 1 0 29 4 1 0 38 32 1 0 27 10 1 0 23 13 1 0 22 16 1 0 5 39 1 0 6 40 1 0 8 41 1 0 11 42 1 0 14 43 1 0 17 44 1 0 19 45 1 0 20 46 1 0 21 47 1 0 25 48 1 0 26 49 1 0 28 50 1 0 29 51 1 0 30 52 1 0 33 53 1 0 35 54 1 0 36 55 1 0 37 56 1 0 M END

Standard InCHIKey	PQOXGHFIRAKOKL-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C30H18O8/c31-17-3-5-19-27(11-17)37-13-23(29(19)35)15-1-7-25(33)21(9-15)22-10-16(2-8-26(22)34)24-14-38-28-12-18(32)4-6-20(28)30(24)36/h1-14,31-34H
SMILES	O=C1C(C2=CC=C(O)C(C3=CC(C4=COC5=CC(O)=CC=C5C4=O)=CC=C3O)=C2)=COC2=CC(O)=CC=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.1	Volume:	504.236 ? Van der Waals volume.
Dense:	1.004	LogP:	3.434 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.777 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.152 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	141.34 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.239	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.758	Fsp³:	0.0
MCE-18:	34.0 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.999	Fluc inhibitor:	0.902 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.95 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.934 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.652	Promiscuous compounds:	0.519

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.169	MDCK Permeability:	-4.815
Pgp-inhibitor:	0.0	Pgp-substrate:	0.283
PAMPA:	0.958 ? 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):	0.013
20% Bioavailability (F20%):	0.964	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.284
Plasma Protein Binding (PPB):	96.258%	Volume Distribution (VD):	-0.333
Fu:	5.877% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.497
OATP1B3 inhibitor:	0.971	BCRP inhibitor:	0.963
BSEP inhibitor:	0.779

ADMET: Metabolism

CYP1A2-inhibitor:	0.937	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.966
CYP2C9-inhibitor:	0.718	CYP2C9-substrate:	0.999
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.894
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	1.0
HLM stability:	0.001 ? 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):

4.385

Half-life (T1/2):

1.67

ADMET: Toxicity

hERG Blockers:	0.459	hERG Blockers (10um):	0.686
Human Hepatotoxicity (H-HT):	0.642	Drug-induced Liver Injury (DILI):	0.933
AMES Toxicity:	0.777	Rat Oral Acute Toxicity:	0.856
Maximum Recommended Daily Dose:	0.995	Skin Sensitization:	0.055
Carcinogencity:	0.862	Eye Corrosion:	0.0
Eye Irritation:	0.908	Respiratory Toxicity:	0.899
Drug-induced Neurotoxicity:	0.269	Ototoxicity:	0.396
Hematotoxicity:	0.056	Drug-induced Nephrotoxicity:	0.22
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.188
A549 Cytotoxicity:	0.822	Hek293 Cytotoxicity:	0.966
BCF:	1.138 ? 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:	4.448 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.689 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.511 ? 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
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	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 NPC529502 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	36184
0.1-0.2	12014
0.2-0.3	1311
0.3-0.4	238
0.4-0.5	58
0.5-0.6	32
0.6-0.7	13
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
0.7917	Intermediate Similarity	NPC242893
0.7872	Intermediate Similarity	NPC234560
0.7719	Intermediate Similarity	NPC611071
0.7679	Intermediate Similarity	NPC607759
0.74	Intermediate Similarity	NPC235428
0.7288	Intermediate Similarity	NPC610903
0.7	Intermediate Similarity	NPC212767
0.6984	Remote Similarity	NPC605730
0.6545	Remote Similarity	NPC209560
0.6545	Remote Similarity	NPC490700
0.6491	Remote Similarity	NPC12175
0.6491	Remote Similarity	NPC139364
0.6481	Remote Similarity	NPC487215
0.6346	Remote Similarity	NPC218490
0.6316	Remote Similarity	NPC12377
0.625	Remote Similarity	NPC203747
0.625	Remote Similarity	NPC609386
0.6207	Remote Similarity	NPC80710
0.6	Remote Similarity	NPC35544
0.6	Remote Similarity	NPC600495
0.5968	Remote Similarity	NPC215311
0.5932	Remote Similarity	NPC40290
0.5932	Remote Similarity	NPC156953
0.5932	Remote Similarity	NPC195763
0.5932	Remote Similarity	NPC191741
0.5833	Remote Similarity	NPC291802
0.5763	Remote Similarity	NPC262623
0.5636	Remote Similarity	NPC324929
0.5625	Remote Similarity	NPC606200
0.5574	Remote Similarity	NPC200060
0.5574	Remote Similarity	NPC55162
0.5556	Remote Similarity	NPC161124
0.5556	Remote Similarity	NPC608523
0.5455	Remote Similarity	NPC125449
0.5441	Remote Similarity	NPC104406
0.5373	Remote Similarity	NPC266572
0.5373	Remote Similarity	NPC149875
0.5278	Remote Similarity	NPC607477
0.5273	Remote Similarity	NPC188074
0.5263	Remote Similarity	NPC38065
0.5217	Remote Similarity	NPC285623
0.5217	Remote Similarity	NPC108859
0.5217	Remote Similarity	NPC609101
0.5211	Remote Similarity	NPC123653
0.5179	Remote Similarity	NPC39426
0.5167	Remote Similarity	NPC181124
0.5167	Remote Similarity	NPC100971
0.5143	Remote Similarity	NPC223701
0.5143	Remote Similarity	NPC472583
0.5143	Remote Similarity	NPC7989
0.5098	Remote Similarity	NPC60558
0.5077	Remote Similarity	NPC215375

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC529502 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6875
0.1-0.2	2245
0.2-0.3	21
0.3-0.4	8
0.4-0.5	0
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
0.5179	Remote Similarity	NPD1510	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