NPASS Compound

Natural Product: NPC518822

Natural Product ID	NPC518822
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7,4'-dihydroxyisoflavone-7-O-(4''-O-methyl)-beta-d-glucopyranoside
IUPAC Name	7-[(2~{S},3~{S},4~{S})-3,4-dihydroxy-6-(hydroxymethyl)-5-methoxy-tetrahydropyran-2-yl]oxy-3-(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]

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 53 56 0 0 0 0 0 0 0 0999 V2000 -6.1324 2.5861 0.1679 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0093 1.7720 0.1474 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3117 0.4287 0.0293 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9060 -0.3765 1.2258 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8938 -1.5334 1.4368 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6979 -2.1088 2.6954 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6177 -0.7700 1.2941 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8379 -0.5958 0.1753 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6572 -1.3228 0.1903 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3749 -0.8335 0.1567 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1117 0.5156 0.1011 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2185 0.9497 0.0692 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2845 0.0764 0.0911 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5864 0.5430 0.0582 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7826 1.7832 0.0076 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6259 -0.3438 0.0811 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0028 0.1327 0.0469 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3728 1.1097 -0.8260 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6565 1.6090 -0.9137 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5932 1.0710 -0.0597 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8888 1.5274 -0.1000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2421 0.0748 0.8389 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9537 -0.4029 0.9032 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2934 -1.6859 0.1372 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0466 -2.0912 0.1671 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0130 -1.2748 0.1469 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7161 -1.7276 0.1793 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5527 -0.9251 -1.1151 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7515 -2.3215 -1.2299 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8272 -0.1586 -1.2773 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6646 0.8125 -2.2566 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7436 2.4915 -0.7600 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7965 2.1615 0.9780 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9291 3.6130 0.4555 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4379 0.3755 -0.0189 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0926 0.2965 2.1183 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7704 -2.2905 0.6350 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9395 -1.1728 1.3575 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7355 -2.0359 2.9502 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6120 0.4823 0.1304 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8549 1.2953 0.0791 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4244 2.0022 0.0258 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6414 1.5500 -1.5135 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9344 2.3817 -1.6090 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4048 1.8052 0.7106 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0157 -0.3223 1.4962 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6569 -1.1690 1.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1167 -2.3912 0.1553 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5196 -2.7977 0.2232 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8810 -0.6640 -1.9566 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1369 -2.8279 -0.6573 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5892 -0.8824 -1.6914 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1251 1.5795 -1.9375 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 4 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 20 22 1 0 22 23 2 0 16 24 2 0 24 25 1 0 25 26 1 0 26 27 2 0 8 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 30 3 1 0 27 10 1 0 26 13 1 0 23 17 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 6 39 1 0 8 40 1 6 11 41 1 0 12 42 1 0 18 43 1 0 19 44 1 0 21 45 1 0 22 46 1 0 23 47 1 0 24 48 1 0 27 49 1 0 28 50 1 6 29 51 1 0 30 52 1 6 31 53 1 0 M END

Standard InCHIKey	BVKFFAQGFXJQBI-YSZROVPYSA-N
Standard InCHI	InChI=1S/C22H22O9/c1-28-21-17(9-23)31-22(20(27)19(21)26)30-13-6-7-14-16(8-13)29-10-15(18(14)25)11-2-4-12(24)5-3-11/h2-8,10,17,19-24,26-27H,9H2,1H3/t17?,19-,20-,21?,22+/m0/s1
SMILES	COC1C(CO)O[C@@H](OC2=CC=C3C(=O)C(C4=CC=C(O)C=C4)=COC3=C2)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.13	Volume:	412.863 ? Van der Waals volume.
Dense:	1.042	LogP:	0.197 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.99 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.232 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	138.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.467	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.757	Fsp³:	0.318
MCE-18:	80.276 ? 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:	0.471	Fluc inhibitor:	0.391 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.944 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.805 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.267	Promiscuous compounds:	0.29

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.829	MDCK Permeability:	-5.115
Pgp-inhibitor:	0.0	Pgp-substrate:	0.395
PAMPA:	0.999 ? 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):	0.373
20% Bioavailability (F20%):	0.385	30% Bioavailability (F30%):	0.702
50% Bioavailability (F50%):	0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.465
Plasma Protein Binding (PPB):	74.615%	Volume Distribution (VD):	0.125
Fu:	30.443% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.667
OATP1B3 inhibitor:	0.974	BCRP inhibitor:	0.109
BSEP inhibitor:	0.364

ADMET: Metabolism

CYP1A2-inhibitor:	0.046	CYP1A2-substrate:	0.065
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.031
CYP2C9-inhibitor:	0.37	CYP2C9-substrate:	0.107
CYP2D6-inhibitor:	0.992	CYP2D6-substrate:	0.032
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.797
HLM stability:	0.0 ? 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):

2.945

Half-life (T1/2):

2.755

ADMET: Toxicity

hERG Blockers:	0.131	hERG Blockers (10um):	0.456
Human Hepatotoxicity (H-HT):	0.52	Drug-induced Liver Injury (DILI):	0.762
AMES Toxicity:	0.701	Rat Oral Acute Toxicity:	0.203
Maximum Recommended Daily Dose:	0.28	Skin Sensitization:	0.699
Carcinogencity:	0.376	Eye Corrosion:	0.0
Eye Irritation:	0.503	Respiratory Toxicity:	0.186
Drug-induced Neurotoxicity:	0.25	Ototoxicity:	0.863
Hematotoxicity:	0.099	Drug-induced Nephrotoxicity:	0.419
Genotoxicity:	0.527	RPMI-8226 Immunitoxicity:	0.082
A549 Cytotoxicity:	0.19	Hek293 Cytotoxicity:	0.406
BCF:	0.576 ? 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:	3.231 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.74 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.948 ? 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
NPO48758	Paecilomyces militaris	Genus	Thermoascaceae	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 NPC518822 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	17240
0.1-0.2	28626
0.2-0.3	3259
0.3-0.4	613
0.4-0.5	91
0.5-0.6	21
0.6-0.7	5
0.7-0.8	1
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
0.7838	Intermediate Similarity	NPC161749
0.7467	Intermediate Similarity	NPC211014
0.6667	Remote Similarity	NPC45165
0.6522	Remote Similarity	NPC181124
0.6386	Remote Similarity	NPC229729
0.6296	Remote Similarity	NPC105511
0.6282	Remote Similarity	NPC25547
0.5976	Remote Similarity	NPC259070
0.5952	Remote Similarity	NPC100720
0.5926	Remote Similarity	NPC487214
0.5904	Remote Similarity	NPC197896
0.5904	Remote Similarity	NPC258035
0.5904	Remote Similarity	NPC313163
0.5814	Remote Similarity	NPC601607
0.5765	Remote Similarity	NPC205076
0.5684	Remote Similarity	NPC231194
0.5595	Remote Similarity	NPC348541
0.5476	Remote Similarity	NPC135345
0.5474	Remote Similarity	NPC51326
0.5342	Remote Similarity	NPC605229
0.5306	Remote Similarity	NPC235575
0.5287	Remote Similarity	NPC73511
0.5281	Remote Similarity	NPC43761
0.5213	Remote Similarity	NPC479405
0.5172	Remote Similarity	NPC603782
0.5158	Remote Similarity	NPC479404
0.5139	Remote Similarity	NPC182428
0.5094	Remote Similarity	NPC76047

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC518822 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4185
0.1-0.2	4856
0.2-0.3	101
0.3-0.4	4
0.4-0.5	2
0.5-0.6	0
0.6-0.7	1
0.7-0.8	1
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
0.7838	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.625	Remote Similarity	NPD3818	Discontinued

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