NPASS Compound

Natural Product: NPC522052

Natural Product ID	NPC522052
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3',5'-Diprenylgenistein
IUPAC Name	5,7-dihydroxy-3-[4-hydroxy-3,5-bis(3-methylbut-2-enyl)phenyl]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 56 58 0 0 0 0 0 0 0 0999 V2000 -2.6589 -4.3616 1.0992 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9188 -4.3919 -0.1807 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2747 -5.6478 -0.6229 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8344 -3.3157 -0.9168 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4673 -2.0764 -0.4857 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5124 -0.9464 -0.3066 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1727 -1.0532 -0.5187 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6322 0.0511 -0.3262 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0663 -0.0940 -0.5614 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5955 -0.7345 -1.6481 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8918 -0.8348 -1.8075 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7564 -0.3373 -0.9522 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1199 -0.4452 -1.1241 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0324 0.0666 -0.2442 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4041 -0.0351 -0.4055 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5444 0.7260 0.8749 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1886 0.8448 1.0657 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6718 1.4962 2.1713 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2874 0.3117 0.1495 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9334 0.4551 0.3820 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5063 1.0597 1.4082 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0976 1.2562 0.0767 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2788 1.3915 0.3016 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7872 2.6840 0.7256 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4786 3.4872 -0.2700 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7094 3.8982 -0.0345 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4627 3.5883 1.2194 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4546 4.7290 -1.0417 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0316 0.2651 0.0960 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3834 0.3569 0.3053 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6872 -5.3836 1.5623 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7213 -4.0686 0.9206 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2591 -3.6131 1.8136 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2957 -5.7372 -1.7486 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1947 -5.6801 -0.3510 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7514 -6.5582 -0.2389 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2914 -3.3509 -1.8484 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2637 -1.7399 -1.1806 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9636 -2.2200 0.4938 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2169 -2.0166 -0.8357 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9056 -1.1526 -2.3664 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5007 -0.9647 -2.0059 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0430 -0.0424 0.3779 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2058 1.1596 1.6189 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6592 1.0704 3.0900 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7616 2.0941 0.2155 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4276 2.5397 1.6432 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9281 3.3064 1.1145 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0662 3.7911 -1.2188 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9921 4.1286 2.0942 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4934 3.9453 1.1932 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4611 2.5374 1.5018 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0305 4.6176 -2.0584 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2879 5.7953 -0.7229 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5133 4.4415 -1.0294 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9674 0.7070 -0.4630 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 2 3 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 20 21 2 0 8 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 3 26 27 1 0 26 28 1 0 23 29 2 0 29 30 1 0 29 6 1 0 20 9 1 0 19 12 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 3 35 1 0 3 36 1 0 4 37 1 0 5 38 1 0 5 39 1 0 7 40 1 0 10 41 1 0 13 42 1 0 15 43 1 0 16 44 1 0 18 45 1 0 22 46 1 0 24 47 1 0 24 48 1 0 25 49 1 0 27 50 1 0 27 51 1 0 27 52 1 0 28 53 1 0 28 54 1 0 28 55 1 0 30 56 1 0 M END

Standard InCHIKey	BGFLPCCZHOCCKB-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H26O5/c1-14(2)5-7-16-9-18(10-17(24(16)28)8-6-15(3)4)20-13-30-22-12-19(26)11-21(27)23(22)25(20)29/h5-6,9-13,26-28H,7-8H2,1-4H3
SMILES	CC(C)=CCC1=CC(C2=COC3=CC(O)=CC(O)=C3C2=O)=CC(CC=C(C)C)=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	406.18	Volume:	432.873 ? Van der Waals volume.
Dense:	0.938	LogP:	4.871 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.558 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.583 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	90.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.48	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.04	Fsp³:	0.24
MCE-18:	21.0 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.985	Fluc inhibitor:	0.651 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.918 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.357 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.522	Promiscuous compounds:	0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.988	MDCK Permeability:	-4.737
Pgp-inhibitor:	0.102	Pgp-substrate:	0.018
PAMPA:	0.764 ? 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):	0.204
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.493
Plasma Protein Binding (PPB):	94.78%	Volume Distribution (VD):	0.316
Fu:	4.844% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.272
OATP1B3 inhibitor:	0.955	BCRP inhibitor:	1.0
BSEP inhibitor:	0.242

ADMET: Metabolism

CYP1A2-inhibitor:	0.105	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.988	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.721	CYP2C9-substrate:	0.914
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.887
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.004	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

6.668

Half-life (T1/2):

1.037

ADMET: Toxicity

hERG Blockers:	0.092	hERG Blockers (10um):	0.599
Human Hepatotoxicity (H-HT):	0.677	Drug-induced Liver Injury (DILI):	0.847
AMES Toxicity:	0.741	Rat Oral Acute Toxicity:	0.877
Maximum Recommended Daily Dose:	0.903	Skin Sensitization:	0.873
Carcinogencity:	0.607	Eye Corrosion:	0.0
Eye Irritation:	0.622	Respiratory Toxicity:	0.943
Drug-induced Neurotoxicity:	0.374	Ototoxicity:	0.509
Hematotoxicity:	0.149	Drug-induced Nephrotoxicity:	0.609
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.09
A549 Cytotoxicity:	0.627	Hek293 Cytotoxicity:	0.766
BCF:	2.028 ? 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:	5.157 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.746 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.193 ? 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
NPO44819	Piscidia erythrina	Genus	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 NPC522052 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	24609
0.1-0.2	22213
0.2-0.3	2414
0.3-0.4	461
0.4-0.5	86
0.5-0.6	49
0.6-0.7	16
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8393	Intermediate Similarity	NPC238279
0.8246	Intermediate Similarity	NPC213659
0.8246	Intermediate Similarity	NPC326109
0.7586	Intermediate Similarity	NPC93552
0.7097	Intermediate Similarity	NPC233918
0.7097	Intermediate Similarity	NPC268059
0.6984	Remote Similarity	NPC128774
0.6774	Remote Similarity	NPC85131
0.6774	Remote Similarity	NPC232947
0.6719	Remote Similarity	NPC485109
0.6562	Remote Similarity	NPC475705
0.6481	Remote Similarity	NPC193792
0.6364	Remote Similarity	NPC39426
0.6364	Remote Similarity	NPC608554
0.6351	Remote Similarity	NPC324447
0.625	Remote Similarity	NPC203077
0.6154	Remote Similarity	NPC48624
0.614	Remote Similarity	NPC38065
0.6102	Remote Similarity	NPC78341
0.6	Remote Similarity	NPC215311
0.6	Remote Similarity	NPC294409
0.6	Remote Similarity	NPC490701
0.5909	Remote Similarity	NPC80962
0.5909	Remote Similarity	NPC169162
0.5806	Remote Similarity	NPC200316
0.5781	Remote Similarity	NPC259166
0.5753	Remote Similarity	NPC303174
0.5735	Remote Similarity	NPC166036
0.5735	Remote Similarity	NPC479305
0.5714	Remote Similarity	NPC194653
0.5714	Remote Similarity	NPC481044
0.5714	Remote Similarity	NPC52889
0.5645	Remote Similarity	NPC239363
0.5625	Remote Similarity	NPC254702
0.5625	Remote Similarity	NPC476055
0.5593	Remote Similarity	NPC87545
0.5571	Remote Similarity	NPC482075
0.5556	Remote Similarity	NPC309154
0.5538	Remote Similarity	NPC104728
0.5538	Remote Similarity	NPC144118
0.5455	Remote Similarity	NPC158874
0.5455	Remote Similarity	NPC20472
0.5429	Remote Similarity	NPC474052
0.5397	Remote Similarity	NPC19980
0.5352	Remote Similarity	NPC74178
0.5352	Remote Similarity	NPC107838
0.5294	Remote Similarity	NPC268204
0.5286	Remote Similarity	NPC280937
0.5231	Remote Similarity	NPC279668
0.5231	Remote Similarity	NPC278323
0.5224	Remote Similarity	NPC38545
0.5217	Remote Similarity	NPC219917
0.5217	Remote Similarity	NPC40942
0.5217	Remote Similarity	NPC606200
0.5211	Remote Similarity	NPC253822
0.5211	Remote Similarity	NPC149875
0.5205	Remote Similarity	NPC474960
0.5152	Remote Similarity	NPC142876
0.5152	Remote Similarity	NPC483637
0.5152	Remote Similarity	NPC264550
0.5152	Remote Similarity	NPC45291
0.5147	Remote Similarity	NPC205046
0.5147	Remote Similarity	NPC608523
0.5139	Remote Similarity	NPC231763
0.5139	Remote Similarity	NPC303197
0.5072	Remote Similarity	NPC301217
0.5072	Remote Similarity	NPC482708
0.5072	Remote Similarity	NPC200694
0.507	Remote Similarity	NPC224714
0.5067	Remote Similarity	NPC123653
0.5063	Remote Similarity	NPC90497

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC522052 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4064
0.1-0.2	5020
0.2-0.3	61
0.3-0.4	4
0.4-0.5	0
0.5-0.6	0
0.6-0.7	1
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
0.6364	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