NPASS Compound

Natural Product: NPC557712

Natural Product ID	NPC557712
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6-hydroxy-3-(4-methoxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	6-hydroxy-3-(4-methoxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-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 54 57 0 0 0 0 0 0 0 0999 V2000 9.8148 0.4845 -0.2730 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0084 -0.4994 0.3509 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6180 -0.4703 0.2335 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8916 -1.4463 0.8575 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4966 -1.4503 0.7626 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8492 -0.4739 0.0421 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3974 -0.5199 -0.0279 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7025 -1.6875 -0.2714 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3947 -1.6853 -0.3264 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6898 -0.5958 -0.1564 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7105 -0.6281 -0.2217 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4553 0.5059 -0.0452 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7994 0.5135 -0.1007 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6490 -0.5404 -0.3300 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4359 -0.4038 -1.4687 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5554 0.3587 -1.3101 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2421 1.8115 -0.9778 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4125 2.5478 -0.8250 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5399 -0.2218 -0.3109 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.7052 -0.6597 -0.8895 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8261 -1.3929 0.3339 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.5919 -2.0274 1.2838 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5309 -0.8469 0.8957 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8998 -1.7776 1.7188 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7786 1.7113 0.2045 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4987 2.8953 0.3912 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5865 1.7694 0.2730 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3153 0.5993 0.0893 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6935 0.6412 0.1553 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2559 1.7537 0.3832 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6158 0.4888 -0.5700 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9904 0.5093 -0.4879 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8167 0.3289 -1.3710 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8489 0.3990 0.1406 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3902 1.4970 -0.0489 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3857 -2.2145 1.4233 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9252 -2.2219 1.2561 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2949 -2.5918 -0.4122 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1389 -1.6054 -0.4191 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0752 -1.4720 -0.4766 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0858 0.3834 -2.2854 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6652 2.2759 -1.8035 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6568 1.9309 -0.0670 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2279 1.9817 -0.8029 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7492 0.5063 0.5230 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8080 -0.2078 -1.7540 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5278 -2.0749 -0.5096 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3308 -2.4895 0.8058 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7332 0.0829 1.4599 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3254 -2.4100 1.2206 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7768 3.4100 -0.4295 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1383 2.6882 0.4649 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0782 1.2506 -1.1344 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5338 1.2895 -0.9894 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 16 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 12 25 2 0 25 26 1 0 25 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 6 31 1 0 31 32 2 0 32 3 1 0 29 7 1 0 28 10 1 0 23 14 1 0 1 33 1 0 1 34 1 0 1 35 1 0 4 36 1 0 5 37 1 0 8 38 1 0 11 39 1 0 14 40 1 6 16 41 1 6 17 42 1 0 17 43 1 0 18 44 1 0 19 45 1 1 20 46 1 0 21 47 1 6 22 48 1 0 23 49 1 1 24 50 1 0 26 51 1 0 27 52 1 0 31 53 1 0 32 54 1 0 M END

Standard InCHIKey	LEPIDOXLUUYARR-MIUGBVLSSA-N
Standard InCHI	InChI=1S/C22H22O10/c1-29-11-4-2-10(3-5-11)13-9-30-15-7-16(14(24)6-12(15)18(13)25)31-22-21(28)20(27)19(26)17(8-23)32-22/h2-7,9,17,19-24,26-28H,8H2,1H3/t17-,19-,20+,21-,22-/m1/s1
SMILES	COC1=CC=C(C2=COC3=CC(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)=C(O)C=C3C2=O)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	446.12	Volume:	421.653 ? Van der Waals volume.
Dense:	1.058	LogP:	0.951 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.645 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.181 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	159.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.37	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:	83.621 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.597	Fluc inhibitor:	0.488 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.965 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.758 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.131	Promiscuous compounds:	0.347

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.15	MDCK Permeability:	-5.245
Pgp-inhibitor:	0.0	Pgp-substrate:	0.088
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):	0.984
20% Bioavailability (F20%):	0.371	30% Bioavailability (F30%):	0.965
50% Bioavailability (F50%):	0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.21
Plasma Protein Binding (PPB):	79.373%	Volume Distribution (VD):	-0.112
Fu:	21.153% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.123
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.965	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.007	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.408
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):

3.429

Half-life (T1/2):

3.209

ADMET: Toxicity

hERG Blockers:	0.068	hERG Blockers (10um):	0.159
Human Hepatotoxicity (H-HT):	0.65	Drug-induced Liver Injury (DILI):	0.967
AMES Toxicity:	0.879	Rat Oral Acute Toxicity:	0.048
Maximum Recommended Daily Dose:	0.069	Skin Sensitization:	0.952
Carcinogencity:	0.429	Eye Corrosion:	0.0
Eye Irritation:	0.253	Respiratory Toxicity:	0.036
Drug-induced Neurotoxicity:	0.033	Ototoxicity:	0.908
Hematotoxicity:	0.378	Drug-induced Nephrotoxicity:	0.775
Genotoxicity:	0.595	RPMI-8226 Immunitoxicity:	0.116
A549 Cytotoxicity:	0.217	Hek293 Cytotoxicity:	0.235
BCF:	0.344 ? 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:	3.074 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.581 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.722 ? 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
NPO24769	Baptisia australis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24769	Baptisia australis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24769	Baptisia australis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24769	Baptisia australis	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

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 NPC557712 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	18656
0.1-0.2	26746
0.2-0.3	3300
0.3-0.4	880
0.4-0.5	224
0.5-0.6	27
0.6-0.7	18
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
0.7703	Intermediate Similarity	NPC45165
0.7703	Intermediate Similarity	NPC135345
0.7342	Intermediate Similarity	NPC229729
0.6962	Remote Similarity	NPC73511
0.6835	Remote Similarity	NPC105511
0.6835	Remote Similarity	NPC258035
0.6835	Remote Similarity	NPC161749
0.6765	Remote Similarity	NPC603503
0.6625	Remote Similarity	NPC603782
0.6429	Remote Similarity	NPC307518
0.642	Remote Similarity	NPC156457
0.6265	Remote Similarity	NPC100720
0.619	Remote Similarity	NPC479402
0.6163	Remote Similarity	NPC479407
0.6118	Remote Similarity	NPC601607
0.6071	Remote Similarity	NPC205076
0.6024	Remote Similarity	NPC197896
0.6024	Remote Similarity	NPC313163
0.6024	Remote Similarity	NPC234739
0.6	Remote Similarity	NPC25547
0.6	Remote Similarity	NPC479401
0.5977	Remote Similarity	NPC48773
0.5862	Remote Similarity	NPC607201
0.5814	Remote Similarity	NPC224462
0.5714	Remote Similarity	NPC259070
0.5714	Remote Similarity	NPC211014
0.5698	Remote Similarity	NPC138540
0.5682	Remote Similarity	NPC479406
0.5595	Remote Similarity	NPC160515
0.5579	Remote Similarity	NPC51326
0.5465	Remote Similarity	NPC95090
0.5465	Remote Similarity	NPC27408
0.5455	Remote Similarity	NPC481043
0.5455	Remote Similarity	NPC80140
0.5408	Remote Similarity	NPC235575
0.5402	Remote Similarity	NPC186807
0.5393	Remote Similarity	NPC486578
0.5349	Remote Similarity	NPC58053
0.5333	Remote Similarity	NPC121522
0.5306	Remote Similarity	NPC231194
0.5222	Remote Similarity	NPC22832
0.5222	Remote Similarity	NPC605067
0.52	Remote Similarity	NPC10467
0.5161	Remote Similarity	NPC487212
0.5158	Remote Similarity	NPC479405
0.5111	Remote Similarity	NPC285197
0.5104	Remote Similarity	NPC479404
0.5068	Remote Similarity	NPC120924

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC557712 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4507
0.1-0.2	4534
0.2-0.3	94
0.3-0.4	10
0.4-0.5	3
0.5-0.6	1
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
0.6835	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5412	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