NPASS Compound

Natural Product: NPC506343

Natural Product ID	NPC506343
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,6,7,3',4'-pentahydroxyisoflavone
IUPAC Name	3-(3,4-dihydroxyphenyl)-5,6,7-trihydroxy-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 32 34 0 0 0 0 0 0 0 0999 V2000 0.0826 1.0078 -1.3978 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4525 0.1581 -0.5515 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4831 -0.5225 0.2093 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9207 -0.2676 0.0449 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7835 -1.3379 -0.0209 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1622 -1.1481 -0.1771 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6295 0.1551 -0.2633 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0013 0.3654 -0.4193 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7938 1.2367 -0.2008 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2696 2.5322 -0.2878 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4309 1.0039 -0.0452 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0212 -1.4489 1.1281 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2354 -1.6890 1.2894 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1491 -1.0736 0.5969 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4790 -1.3946 0.8362 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4227 -0.7310 0.0922 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7647 -1.0138 0.2917 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1152 0.2172 -0.8592 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0645 0.8814 -1.6042 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7748 0.5018 -1.0606 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4237 1.4557 -2.0149 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7807 -0.1337 -0.3420 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4072 -2.3371 0.0473 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8330 -1.9936 -0.2278 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4075 1.1700 0.0764 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2241 2.9611 -1.2221 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7522 1.8411 0.0067 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8012 -1.9658 1.7106 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7778 -2.1343 1.5745 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3280 -0.5244 0.9650 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0687 1.9007 -1.5807 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0017 2.3280 -1.7290 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 9 11 2 0 3 12 2 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 16 18 2 0 18 19 1 0 18 20 1 0 20 21 1 0 20 22 2 0 22 2 1 0 11 4 1 0 22 14 1 0 5 23 1 0 6 24 1 0 8 25 1 0 10 26 1 0 11 27 1 0 12 28 1 0 15 29 1 0 17 30 1 0 19 31 1 0 21 32 1 0 M END

Standard InCHIKey	BIDDAFIPYBBDES-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H10O7/c16-8-2-1-6(3-9(8)17)7-5-22-11-4-10(18)14(20)15(21)12(11)13(7)19/h1-5,16-18,20-21H
SMILES	O=C1C(C2=CC=C(O)C(O)=C2)=COC2=CC(O)=C(O)C(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.04	Volume:	282.767 ? Van der Waals volume.
Dense:	1.068	LogP:	1.085 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.151 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.324 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	131.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.434	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.613	Fsp³:	0.0
MCE-18:	19.0 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.873	Fluc inhibitor:	0.495 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.939 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.303 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.705	Promiscuous compounds:	0.899

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.262	MDCK Permeability:	-4.798
Pgp-inhibitor:	0.0	Pgp-substrate:	0.024
PAMPA:	0.904 ? 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):	0.1
20% Bioavailability (F20%):	0.987	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.853
Plasma Protein Binding (PPB):	92.121%	Volume Distribution (VD):	-0.55
Fu:	7.06% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.889
OATP1B3 inhibitor:	0.915	BCRP inhibitor:	0.953
BSEP inhibitor:	0.01

ADMET: Metabolism

CYP1A2-inhibitor:	0.048	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.012
CYP2C9-inhibitor:	0.08	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.353	CYP2D6-substrate:	0.948
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.184
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.447 ? 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):

14.746

Half-life (T1/2):

1.766

ADMET: Toxicity

hERG Blockers:	0.099	hERG Blockers (10um):	0.795
Human Hepatotoxicity (H-HT):	0.383	Drug-induced Liver Injury (DILI):	0.843
AMES Toxicity:	0.65	Rat Oral Acute Toxicity:	0.471
Maximum Recommended Daily Dose:	0.794	Skin Sensitization:	0.997
Carcinogencity:	0.443	Eye Corrosion:	0.064
Eye Irritation:	0.991	Respiratory Toxicity:	0.456
Drug-induced Neurotoxicity:	0.004	Ototoxicity:	0.795
Hematotoxicity:	0.022	Drug-induced Nephrotoxicity:	0.014
Genotoxicity:	0.974	RPMI-8226 Immunitoxicity:	0.006
A549 Cytotoxicity:	0.958	Hek293 Cytotoxicity:	0.246
BCF:	1.027 ? 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:	3.743 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.532 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.266 ? 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
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1023/A:1002708427984]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	Oil	n.a.	n.a.	Database[FooDB]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	Leaves	n.a.		Database[FooDB]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1565	Lepidium sativum	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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 NPC506343 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	37216
0.1-0.2	10891
0.2-0.3	1424
0.3-0.4	225
0.4-0.5	87
0.5-0.6	9
0.6-0.7	3
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
0.7143	Intermediate Similarity	NPC38065
0.6604	Remote Similarity	NPC245382
0.6275	Remote Similarity	NPC242893
0.6102	Remote Similarity	NPC482730
0.5962	Remote Similarity	NPC324929
0.5932	Remote Similarity	NPC20472
0.5769	Remote Similarity	NPC39426
0.5577	Remote Similarity	NPC188074
0.5472	Remote Similarity	NPC218490
0.5283	Remote Similarity	NPC193792
0.5263	Remote Similarity	NPC269451
0.5185	Remote Similarity	NPC608554
0.5085	Remote Similarity	NPC209487

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC506343 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7305
0.1-0.2	1826
0.2-0.3	13
0.3-0.4	5
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
0.5769	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