NPASS Compound

Natural Product: NPC476055

Natural Product ID	NPC476055
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Fremontin
IUPAC Name	3-[2,4-dihydroxy-5-(2-methylbut-3-en-2-yl)phenyl]-5,7-dihydroxychromen-4-one
Synonyms	Fremontin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL523643
PubChem CID	5487268
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 44 46 0 0 0 0 0 0 0 0999 V2000 -2.7767 -2.4888 0.9714 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1684 -1.3358 1.4761 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6136 -0.2136 0.6152 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3599 -0.8220 -0.5704 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5984 0.6141 1.3768 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4626 0.5809 0.1182 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1644 0.2498 0.4652 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1154 1.0211 -0.0206 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2584 0.6917 0.3313 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8758 1.2245 1.4550 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1150 0.9328 1.7798 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8673 0.1260 1.0840 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1671 -0.1625 1.4497 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9563 -1.0159 0.7097 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4052 -1.5923 -0.4362 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1079 -1.3074 -0.8054 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3302 -0.4545 -0.0593 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0318 -0.1698 -0.4296 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5376 -0.6900 -1.4619 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5222 -1.8675 -1.9487 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2588 -1.2972 1.0871 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3856 2.1002 -0.8379 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6712 2.4500 -1.1978 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7120 1.6608 -0.6982 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0099 1.9826 -1.0386 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6991 2.8589 -1.3116 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7856 -2.6050 -0.1014 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4630 -3.2700 1.6482 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1655 -1.2038 2.5444 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6813 -1.1061 -1.3872 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1280 -0.1086 -0.9360 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8487 -1.7420 -0.1977 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4921 1.7075 1.2256 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4305 0.4480 2.4612 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6637 0.3009 1.1996 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9364 -0.5851 1.0989 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2961 1.8985 2.0653 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5803 0.3015 2.3541 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9986 -2.2652 -1.0368 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7118 -2.8330 -2.1468 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8183 -0.6430 1.6187 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8895 3.3037 -1.8448 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2683 2.9521 -1.0620 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2527 2.3737 -2.0340 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 3 5 1 0 3 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 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 16 20 1 0 14 21 1 0 8 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 22 26 1 0 24 6 1 0 18 9 1 0 17 12 1 0 1 27 1 0 1 28 1 0 2 29 1 0 4 30 1 0 4 31 1 0 4 32 1 0 5 33 1 0 5 34 1 0 5 35 1 0 7 36 1 0 10 37 1 0 13 38 1 0 15 39 1 0 20 40 1 0 21 41 1 0 23 42 1 0 25 43 1 0 26 44 1 0 M END

Standard InCHIKey	XWUWFNSZQDCXCD-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H18O6/c1-4-20(2,3)13-7-11(14(22)8-15(13)23)12-9-26-17-6-10(21)5-16(24)18(17)19(12)25/h4-9,21-24H,1H2,2-3H3
SMILES	C=CC(C)(C)c1cc(c2coc3cc(cc(c3c2=O)O)O)c(cc1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.11	Volume:	357.82 ? Van der Waals volume.
Dense:	0.99	LogP:	3.072 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.74 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.725 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	19.0
TPSA:	111.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.533	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.06	Fsp³:	0.15
MCE-18:	22.0 ? 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:	0.776	Fluc inhibitor:	0.283 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.829 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.619 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.495	Promiscuous compounds:	0.213

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.134	MDCK Permeability:	-4.847
Pgp-inhibitor:	0.097	Pgp-substrate:	0.037
PAMPA:	0.158 ? 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%):	0.932	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.781
Plasma Protein Binding (PPB):	97.655%	Volume Distribution (VD):	-0.097
Fu:	2.314% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.999
BSEP inhibitor:	0.554

ADMET: Metabolism

CYP1A2-inhibitor:	0.953	CYP1A2-substrate:	0.954
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.099
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.943
CYP2D6-inhibitor:	0.988	CYP2D6-substrate:	0.997
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.963
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	1.0
HLM stability:	0.946 ? 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):

0.864

Half-life (T1/2):

1.788

ADMET: Toxicity

hERG Blockers:	0.084	hERG Blockers (10um):	0.627
Human Hepatotoxicity (H-HT):	0.333	Drug-induced Liver Injury (DILI):	0.652
AMES Toxicity:	0.437	Rat Oral Acute Toxicity:	0.736
Maximum Recommended Daily Dose:	0.954	Skin Sensitization:	0.594
Carcinogencity:	0.573	Eye Corrosion:	0.043
Eye Irritation:	0.995	Respiratory Toxicity:	0.951
Drug-induced Neurotoxicity:	0.145	Ototoxicity:	0.227
Hematotoxicity:	0.031	Drug-induced Nephrotoxicity:	0.065
Genotoxicity:	0.969	RPMI-8226 Immunitoxicity:	0.111
A549 Cytotoxicity:	0.741	Hek293 Cytotoxicity:	0.836
BCF:	1.458 ? 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:	4.162 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.388 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.863 ? 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
NPO11841	Psorothamnus arborescens	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[16441066]
NPO11841	Psorothamnus arborescens	Species	Fabaceae	Eukaryota	root	n.a.	n.a.	PMID[16441066]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26469557]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2681536]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11841	Psorothamnus arborescens	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11841	Psorothamnus arborescens	Species	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

Activity Type	# Activity
Inhibition	14
IC50	4

Activity Type	# Activity
Cell line	2
Organism	16

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
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	134000.0	nM	PMID[24953953]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	78500.0	nM	DOI[10.6019/CHEMBL1201861]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	93.0	%	PMID[10075763]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	24.0	%	PMID[26854381]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	0.0	%	PMID[18494522]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	65.0	%	PMID[18494522]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	87.0	%	PMID[19761234]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	81.0	%	PMID[12027747]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	90.0	%	PMID[11754614]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	58.0	%	PMID[11754614]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	92.0	%	PMID[15165157]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	123000.0	nM	PMID[23848163]
NPT471	Organism	Trypanosoma brucei brucei	Trypanosoma brucei brucei	IC50	=	75300.0	nM	PMID[19117486]

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 NPC476055 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	28682
0.1-0.2	19116
0.2-0.3	1656
0.3-0.4	325
0.4-0.5	39
0.5-0.6	29
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
0.6769	Remote Similarity	NPC485109
0.6207	Remote Similarity	NPC87545
0.5821	Remote Similarity	NPC232947
0.5781	Remote Similarity	NPC279668
0.5692	Remote Similarity	NPC45291
0.569	Remote Similarity	NPC193792
0.56	Remote Similarity	NPC484048
0.5593	Remote Similarity	NPC39426
0.5593	Remote Similarity	NPC608554
0.5469	Remote Similarity	NPC19980
0.5455	Remote Similarity	NPC264550
0.5429	Remote Similarity	NPC475705
0.5417	Remote Similarity	NPC231763
0.541	Remote Similarity	NPC38065
0.5397	Remote Similarity	NPC78341
0.5385	Remote Similarity	NPC309154
0.5362	Remote Similarity	NPC213659
0.5362	Remote Similarity	NPC326109
0.5312	Remote Similarity	NPC294409
0.5312	Remote Similarity	NPC490701
0.5294	Remote Similarity	NPC93552
0.5231	Remote Similarity	NPC239363
0.5217	Remote Similarity	NPC238279
0.5205	Remote Similarity	NPC303197
0.5152	Remote Similarity	NPC200316
0.5143	Remote Similarity	NPC85131
0.5075	Remote Similarity	NPC278323
0.5075	Remote Similarity	NPC194653
0.5075	Remote Similarity	NPC481044
0.507	Remote Similarity	NPC606200
0.5068	Remote Similarity	NPC474052

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476055 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5688
0.1-0.2	3435
0.2-0.3	24
0.3-0.4	2
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
0.5593	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