NPASS Compound

Natural Product: NPC590770

Natural Product ID	NPC590770
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Daidzein G3
IUPAC Name	7-[(3~{R},4~{R},5~{R},6~{S})-4,5-dihydroxy-3-methoxy-6-methyl-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 52 55 0 0 0 0 0 0 0 0999 V2000 -3.5979 3.0145 0.8229 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2772 1.6816 1.0699 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9818 0.8869 0.2120 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0524 -0.0124 -0.6279 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9023 0.6972 -0.8437 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6383 0.3246 -0.5110 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3845 -0.8697 0.1089 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9504 -1.1774 0.4179 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9291 -0.2880 0.0937 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2612 -0.5642 0.3869 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5319 -1.6484 0.9544 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2458 0.3410 0.0555 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6521 0.0780 0.3509 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6198 0.3154 -0.5808 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9300 0.0576 -0.2707 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3054 -0.4350 0.9538 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6504 -0.6819 1.2239 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3160 -0.6680 1.8797 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0004 -0.4176 1.5915 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8908 1.5165 -0.5671 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6349 1.7656 -0.8379 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6622 0.9132 -0.5312 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3741 1.2143 -0.8315 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7954 -0.2723 -1.7833 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1347 -0.4700 -1.5444 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6121 -1.5286 -2.5400 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4417 -1.0072 -0.1715 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.8501 -0.9874 -0.0478 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9105 -0.0923 0.9220 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1978 -0.8838 1.8295 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6986 3.1039 0.9966 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4613 3.2522 -0.2728 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0129 3.7232 1.4306 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6117 1.4950 -0.4436 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9090 -0.9774 -0.1349 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1324 -1.6058 0.3846 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2129 -2.1015 0.9055 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3498 0.7066 -1.5613 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7187 0.2388 -0.9962 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0648 -1.4624 0.7244 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6287 -1.0594 2.8478 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2293 -0.6077 2.3361 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6815 2.2094 -0.8165 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1401 2.1647 -1.3286 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7557 0.4427 -1.7721 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3314 -2.5377 -2.1706 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0935 -1.2781 -3.5015 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6869 -1.4064 -2.6785 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0838 -2.0330 -0.0854 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2464 -1.6496 -0.6835 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7121 0.4262 1.4679 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4681 -1.8462 1.7626 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 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 2 0 12 20 2 0 20 21 1 0 21 22 1 0 22 23 2 0 4 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 3 1 0 23 6 1 0 22 9 1 0 19 13 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 6 4 35 1 0 7 36 1 0 8 37 1 0 14 38 1 0 15 39 1 0 17 40 1 0 18 41 1 0 19 42 1 0 20 43 1 0 23 44 1 0 25 45 1 6 26 46 1 0 26 47 1 0 26 48 1 0 27 49 1 6 28 50 1 0 29 51 1 1 30 52 1 0 M END

Standard InCHIKey	CVKPCUMQRIIKCD-YUESUMPFSA-N
Standard InCHI	InChI=1S/C22H22O8/c1-11-18(24)20(26)21(27-2)22(29-11)30-14-7-8-15-17(9-14)28-10-16(19(15)25)12-3-5-13(23)6-4-12/h3-11,18,20-24,26H,1-2H3/t11-,18-,20+,21+,22?/m0/s1
SMILES	CO[C@H]1C(OC2=CC=C3C(=O)C(C4=CC=C(O)C=C4)=COC3=C2)O[C@@H](C)[C@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	414.13	Volume:	404.072 ? Van der Waals volume.
Dense:	1.025	LogP:	0.951 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.372 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.535 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	118.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.593	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.744	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:	0.485	Fluc inhibitor:	0.408 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.943 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.608 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.255	Promiscuous compounds:	0.18

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.613	MDCK Permeability:	-5.116
Pgp-inhibitor:	0.004	Pgp-substrate:	0.432
PAMPA:	0.998 ? 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):	0.025
20% Bioavailability (F20%):	0.107	30% Bioavailability (F30%):	0.155
50% Bioavailability (F50%):	0.831

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.222
Plasma Protein Binding (PPB):	89.251%	Volume Distribution (VD):	0.029
Fu:	13.357% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.954
OATP1B3 inhibitor:	0.958	BCRP inhibitor:	0.063
BSEP inhibitor:	0.775

ADMET: Metabolism

CYP1A2-inhibitor:	0.009	CYP1A2-substrate:	0.775
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.367
CYP2C9-inhibitor:	0.254	CYP2C9-substrate:	0.402
CYP2D6-inhibitor:	0.244	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
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):

3.736

Half-life (T1/2):

2.603

ADMET: Toxicity

hERG Blockers:	0.155	hERG Blockers (10um):	0.492
Human Hepatotoxicity (H-HT):	0.425	Drug-induced Liver Injury (DILI):	0.772
AMES Toxicity:	0.628	Rat Oral Acute Toxicity:	0.216
Maximum Recommended Daily Dose:	0.234	Skin Sensitization:	0.535
Carcinogencity:	0.366	Eye Corrosion:	0.001
Eye Irritation:	0.785	Respiratory Toxicity:	0.172
Drug-induced Neurotoxicity:	0.073	Ototoxicity:	0.651
Hematotoxicity:	0.129	Drug-induced Nephrotoxicity:	0.402
Genotoxicity:	0.54	RPMI-8226 Immunitoxicity:	0.099
A549 Cytotoxicity:	0.14	Hek293 Cytotoxicity:	0.421
BCF:	1.169 ? 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:	3.969 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.946 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.614 ? 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
NPO32477	Streptomyces sp.	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.1007/s00253-016-7823-y]
NPO32477	Streptomyces sp.	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[23013356]
NPO32477	Streptomyces sp.	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[28625960]
NPO32477	Streptomyces sp.	Under-species	n.a.	n.a.	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 NPC590770 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	12050
0.1-0.2	33674
0.2-0.3	3424
0.3-0.4	574
0.4-0.5	106
0.5-0.6	21
0.6-0.7	6
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
0.7671	Intermediate Similarity	NPC211014
0.6883	Remote Similarity	NPC161749
0.6716	Remote Similarity	NPC181124
0.6447	Remote Similarity	NPC25547
0.6341	Remote Similarity	NPC43761
0.6282	Remote Similarity	NPC487214
0.6125	Remote Similarity	NPC259070
0.5952	Remote Similarity	NPC229729
0.5802	Remote Similarity	NPC45165
0.5732	Remote Similarity	NPC348541
0.5644	Remote Similarity	NPC76047
0.5493	Remote Similarity	NPC605229
0.5476	Remote Similarity	NPC105511
0.5426	Remote Similarity	NPC51326
0.5312	Remote Similarity	NPC231194
0.5294	Remote Similarity	NPC258035
0.5286	Remote Similarity	NPC182428
0.5205	Remote Similarity	NPC479067
0.5172	Remote Similarity	NPC100720
0.5135	Remote Similarity	NPC136095
0.5135	Remote Similarity	NPC100971
0.5135	Remote Similarity	NPC209560
0.5135	Remote Similarity	NPC490700
0.5116	Remote Similarity	NPC197896
0.5116	Remote Similarity	NPC313163
0.5102	Remote Similarity	NPC235575
0.5059	Remote Similarity	NPC160515
0.5056	Remote Similarity	NPC601607

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC590770 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3407
0.1-0.2	5605
0.2-0.3	131
0.3-0.4	2
0.4-0.5	2
0.5-0.6	2
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
0.6883	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5238	Remote Similarity	NPD3818	Discontinued
0.5205	Remote Similarity	NPD2796	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