NPASS Compound

Natural Product: NPC507454

Natural Product ID	NPC507454
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 3'-O-alpha-L-rhamnopyranoside
IUPAC Name	7-hydroxy-3-[4-hydroxy-3-[(2~{R},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-phenyl]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 50 53 0 0 0 0 0 0 0 0999 V2000 4.1220 -2.5278 1.3657 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8721 -1.2963 0.5346 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1805 -0.1241 1.2158 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5051 0.9127 0.5554 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1838 0.5283 0.4369 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0233 1.0322 0.8700 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1470 0.3512 0.5475 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3725 0.7818 0.9401 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5835 0.0248 0.5730 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6601 -1.3409 0.6829 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7671 -1.9849 0.3425 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8322 -1.3717 -0.1094 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9777 -2.0888 -0.4566 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0928 -1.4526 -0.9292 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2277 -2.1551 -1.2739 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0654 -0.0811 -1.0577 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9239 0.6343 -0.7118 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8099 -0.0103 -0.2388 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6794 0.7112 0.1024 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6623 1.9605 -0.0175 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4548 1.9295 1.6808 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3438 2.6383 2.0267 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9115 2.1750 1.6104 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9823 2.9469 2.0004 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0443 1.0957 -0.8541 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1178 1.9343 -1.5151 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0877 -0.1893 -1.6179 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8119 -0.0166 -2.7801 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6716 -1.2940 -0.7448 C 0 0 1 0 0 0 0 0 0 0 0 0 6.0047 -0.9427 -0.4950 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4088 -2.5259 2.1987 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1486 -2.5515 1.7736 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9167 -3.4042 0.7342 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7990 -1.2873 0.2636 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7275 1.8190 1.1127 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0855 -0.5714 -0.0474 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7883 -1.8831 1.0569 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9902 -3.1760 -0.3513 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3052 -2.5046 -2.2162 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9103 0.4870 -1.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8854 1.7237 -0.8078 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4660 2.2337 1.9720 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4348 3.5441 2.6137 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3232 3.7505 1.5048 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0030 1.6535 -0.8673 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5513 2.3891 -2.2662 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0263 -0.4998 -1.8236 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2600 0.2674 -3.5545 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6372 -2.2666 -1.2670 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1455 0.0215 -0.4285 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 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 8 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 4 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 2 1 0 23 6 1 0 19 9 1 0 18 12 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 6 4 35 1 1 7 36 1 0 10 37 1 0 13 38 1 0 15 39 1 0 16 40 1 0 17 41 1 0 21 42 1 0 22 43 1 0 24 44 1 0 25 45 1 1 26 46 1 0 27 47 1 6 28 48 1 0 29 49 1 6 30 50 1 0 M END

Standard InCHIKey	QBHNFPJUSZDRKX-FHVYTQILSA-N
Standard InCHI	InChI=1S/C21H20O9/c1-9-17(24)19(26)20(27)21(29-9)30-16-6-10(2-5-14(16)23)13-8-28-15-7-11(22)3-4-12(15)18(13)25/h2-9,17,19-24,26-27H,1H3/t9-,17+,19+,20-,21-/m1/s1
SMILES	C[C@H]1O[C@H](OC2=CC(C3=COC4=CC(O)=CC=C4C3=O)=CC=C2O)[C@H](O)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	416.11	Volume:	395.567 ? Van der Waals volume.
Dense:	1.052	LogP:	0.591 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.093 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.076 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	149.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.423	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.813	Fsp³:	0.286
MCE-18:	84.259 ? 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:	0.524	Fluc inhibitor:	0.338 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.959 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.665 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.268	Promiscuous compounds:	0.431

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.226	MDCK Permeability:	-5.186
Pgp-inhibitor:	0.0	Pgp-substrate:	0.939
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):	0.049
20% Bioavailability (F20%):	0.877	30% Bioavailability (F30%):	0.967
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.166
Plasma Protein Binding (PPB):	84.99%	Volume Distribution (VD):	-0.016
Fu:	17.971% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.258
OATP1B3 inhibitor:	0.558	BCRP inhibitor:	0.387
BSEP inhibitor:	0.08

ADMET: Metabolism

CYP1A2-inhibitor:	0.04	CYP1A2-substrate:	0.187
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.022
CYP2C9-inhibitor:	0.022	CYP2C9-substrate:	0.301
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.026
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.969
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.019 ? 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):

3.73

Half-life (T1/2):

3.4

ADMET: Toxicity

hERG Blockers:	0.085	hERG Blockers (10um):	0.436
Human Hepatotoxicity (H-HT):	0.441	Drug-induced Liver Injury (DILI):	0.671
AMES Toxicity:	0.84	Rat Oral Acute Toxicity:	0.193
Maximum Recommended Daily Dose:	0.332	Skin Sensitization:	0.691
Carcinogencity:	0.258	Eye Corrosion:	0.0
Eye Irritation:	0.66	Respiratory Toxicity:	0.128
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.801
Hematotoxicity:	0.159	Drug-induced Nephrotoxicity:	0.306
Genotoxicity:	0.536	RPMI-8226 Immunitoxicity:	0.141
A549 Cytotoxicity:	0.354	Hek293 Cytotoxicity:	0.483
BCF:	0.764 ? 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:	3.319 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.238 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.742 ? 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
NPO62062	Streptomyces diannanensis	Genus	Streptomycetaceae	Bacteria	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 NPC507454 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	17525
0.1-0.2	28757
0.2-0.3	2774
0.3-0.4	653
0.4-0.5	121
0.5-0.6	20
0.6-0.7	5
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
0.6709	Remote Similarity	NPC211014
0.6625	Remote Similarity	NPC258035
0.662	Remote Similarity	NPC139364
0.6296	Remote Similarity	NPC259070
0.6	Remote Similarity	NPC25547
0.5904	Remote Similarity	NPC348541
0.5789	Remote Similarity	NPC231194
0.5783	Remote Similarity	NPC605730
0.5647	Remote Similarity	NPC161749
0.5618	Remote Similarity	NPC48773
0.5618	Remote Similarity	NPC479407
0.5541	Remote Similarity	NPC203747
0.5412	Remote Similarity	NPC160515
0.5395	Remote Similarity	NPC12377
0.5325	Remote Similarity	NPC80710
0.5287	Remote Similarity	NPC105511
0.5222	Remote Similarity	NPC229729
0.5211	Remote Similarity	NPC234560
0.519	Remote Similarity	NPC35544
0.5132	Remote Similarity	NPC209560
0.5132	Remote Similarity	NPC490700
0.5132	Remote Similarity	NPC609386
0.5068	Remote Similarity	NPC242893
0.5063	Remote Similarity	NPC109187
0.5055	Remote Similarity	NPC606560

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC507454 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4194
0.1-0.2	4884
0.2-0.3	59
0.3-0.4	11
0.4-0.5	0
0.5-0.6	2
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
0.5647	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5057	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